This action might not be possible to undo. Are you sure you want to continue?
→ medial thigh Inguinal Ligament → anterior thigh Bladder – most anterior - abdominal and pelvic structure Uterus (female) Rectum – most posterior Pelvic Inlet = Pelvic Brim - Sacral Promontory - Margins of ala - Linea Terminalis - Arcuate line - Pectineal line - Pubic crest Layers - Bony Wall - Musculature - Nerves - Parietal Pelvic Fascia - Vessels - Arteries (medial) - Veins - Nerves (lateral) - Peritoneum Greater Sciatic Foramen - Superior Gluteal nerves/vessels ------Prirformis----------------------------------- Inferior Gluteal nerves/vessels - Sciatic Nerve - Posterior cutaneous nerve of thigh - Nerve to quadratus femoris - Pudendal nerve → exit pelvis – only sensory - Internal pudendal vessels → exit pelvis - Nerve to obturator internus → exit pelvis Lesser Sciatic Foramen - Obturator internus - Pudendal nerve → return into pelvis - Internal pudendal vessels → return into pelvis - Nerve to obturator internus → return into pelvis 2) Review blood supply and lymphatic drainage of the pelvis and perineum Arteries of Female Pelvis Internal Iliac a. (anterior branch) → Obturator a. ***may arise from external pudendal artery
→ Umbillical a. → Superior Vesicle a. → Uterine a. - similar to artery to ductus deferens in men - tortuous - ureter runs under – “water under the bridge” → Ascending branch → uterus → Descending branch → cervix and vagina → Vaginal a. → Inferior Vesicle a. → Middle Rectal a. → Internal Pudendal a. → Inferior Rectal a. → Inferior Gluteal a. – pass between S2 and S3 Internal Iliac a. (posterior branch) – parietal branches – supply posterior wall → Iliolumbar a. → Lateral Sacral a. → Superior Gluteal a. – pass between lumbar sacral trunk and S1 Arteries of Male Pelvis Internal Iliac a. (anterior branch) → Obturator a. ***may arise from external pudendal artery → Umbilical a. → Superior Vesicle a. → Artery of ductus deferens → Inferior Vesicle a. → Middle Rectal a. → Internal Pudendal a. → Inferior Rectal a. → Inferior Gluteal – pass between S2 and S3 Internal Iliac a. (posterior branch) – parietal branches – supply posterior wall → Iliolumbar a. → Lateral Sacral a. → Superior Gluteal a. – pass between lumbar sacral trunk and S1 Lymphatics Inferior Phrenic lymph nodes Lumbar lymph nodes - Pre-aortic – celiac, superior mesenteric, inferior mesenteric - Left Lateral Aortic - Right Lateral Aortic (Caval) - Retroaortic Iliac lymph nodes - Common Iliac - External Iliac - Internal Iliac Inguinal lymph nodes - Superficial – horizontal, vertical (T-shaped) - Deep
Sacral lymph nodes Collateral Circulation in Pelvis Lumbar a. ↔ Iliolumbar a. Median Sacral a. ↔ Lateral Sacral a. Superior Rectal a. ↔ Middle Rectal a. Inferior Gluteal a. ↔ Deep artery of the thigh Veins of Pelvis Pelvic Organs → Internal Vertebral (Batson’s) Venous Plexus - cancer can metastasize to brain and spinal cord - cancer can spread to heart and lungs Lymphatic Drainage - Fundus of Uterus near Round Ligament – superficial inguinal lymph nodes - Lower Uterine body, Cervix, and Bladder – internal and external iliac lymph nodes - Ovaries, Uterine Tubes, Upper Uterine Body, Testis – para-aortic lymph nodes - Glands Penis (Clitoris) and Labium minor – deep inguinal and external iliac lymph nodes - Prostate and Lower Rectum – internal iliac lymph nodes 3) Nerves of the pelvis (somatic, autonomic – SNS, PNS) Pelvic Nerves - Somatic – ventral rami → motor - Sacral Plexus – Lumbosacral trunk (L4, L5) + S1-S4 - Coccygeal Plexus – S4, S5 + Coccygeal nerves - Autonomic - Sacral Splanchnic (Sacral Plexus) – SNS – lower limb - Pudendal Nerve – S2, S3, S4 - Coccygeal Ganglion (Impar) - Periarterial Plexus – SNS – vasomotor - Hypogastric Plexus – pelvic organs - Superior Hypogastric plexus (SNS) - Right and Left Hypogastric Nerves (SNS) - Inferior Hypogastric plexus → join pelvic splanchnic (mixed – SNS/PNS) - Pelvic Splanchnic (Pelvic Plexus) – PNS - name changes depending on location (ex: prostatic plexus, vesicle plexus, etc.) - Cavernous nerve → supplies penis Innervation of Bladder - SNS (T11-L2) → contract internal sphincter → relax detrusor muscle - PNS (S2-S4) → relax internal sphincter → contract detrusor muscle - Pudendal → voluntary control of external sphincter
pain line occurs in middle of sigmoid colon 5) Review the innervation of pelvic organs 6) Clinical Correlates *Suprapubic Cystostomy – drain bladder if urethra is obstructed (ex: enlarged prostate) or injured (torn urethra) *Pelvic Ultrasound – require full bladder to help sound waves travel better → better visualization of pelvic organs *Digital Rectal Exam .Below – PNS (S2-S4) .Males – palpate posterior lobe of prostate *Culdoscopy – insertion through posterior vaginal fornix to examine ovaries or uterine tubes *Culdocentesis – drainage of pelvic abscess. S5 *Anesthesia for Childbirth .Large Intestine pain does not correlate with peritoneum .Caudal Epidural Block – catheter into sacral canal → feel contractions but not pain of childbirth .Above – SNS (T12-L2) . or blood through the posterior vaginal fornix *Anal Reflex – S4.loss of voluntary emptying of bladder *Autonomous Bladder – detrusor flaccid → bladder overfills → overflows .4) Concept of the pelvic pain line *Pelvic Pain Line – corresponds with inferior limit of peritoneum .Spinal Anesthesia – lumbar puncture → anesthesia inferior to waist – cannot feel contractions .Females – palpate Rectouterine (Douglas) pouch .Pudendal Nerve Block – ischial spine landmark → S2-S4 dermatomes + ¼ of vagina *Benign Prostatic Hyperplasia – middle/intermediate lobe most commonly enlarged *Atonic Bladder – L2 injury → detrusor and external sphincter relax. fluid.usually present in early stages of spinal shock *Automatic Reflex Bladder – reflex contraction every 2-4 hours . internal sphincter contracted → urine dribble .
Bayesian Probability – Adjust a person’s prior risk. Prior Risk Carrier = 1/2 Non-Carrier = 1/2 Conditional Risk – what is the patients risk of being normal? . most often of being a carrier of a mutant gene .ex: unaffected children.Age 30 = 10% are clinically affected Carrier: 9/10 Non-Carrier = 10/10 Joint Risk – (Prior Risk) x (Conditional Risk) Carrier = (1/2) x (9/10) = 9/20 Non-Carrier = (1/2) x (10/10) = 10/20 . negative lab tests.Conditional Risk – taking into account further information to lower the risk → posterior (modified) risk . etc.
what is the risk of their children being affected? Joint Risk – (Prior Risk) x (Conditional Risk) Carrier = (1/50) x (9/16) = 9/800 Non-Carrier = (49/50) x (4/4) = 784/800 Posterior Risk – (Joint Risk)/(Sum of Joint Probabilities) Carrier = (9/800)/(9/800 + 784/800) = (9/800)/(793/800) = 9/800 x 800/793 = 9/793 1/88 Non-Carrier = (784/800)/(9/800 + 784/800) = (784/800)/(793/800) = 784/800 x 800/793 = 784/793 Stephan and Kim’s Risk of being carriers = 1/88 Charlotte’s Risk of being having a child with Huntington’s Disease 1/88 [risk of being a carrier] x 1/2 [Kim passing on bad allele] x 1/2 [Stephan passing on bad allele] = 1/352 .if both are not carriers.Posterior Risk – (Joint Risk)/(Sum of Joint Probabilities) Carrier = (9/20)/(9/20 + 10/20) = (9/20)/(19/20) = 9/20 x 20/19 = 9/19 Non-Carrier = (10/20)/(9/20 + 10/20) = (10/20)/(19/20) = 10/20 x 20/19 = 10/19 Charlotte’s Risk of being a carrier = 9/19 . now it is 9/19 Charlotte’s Risk of being having a child with Huntington’s Disease 9/19 [risk of being a carrier] x 1/2 [passing on bad allle] x 99/100 [Penetrance] = 891/3800 Prior Risk – risk that both Stephan and Kim are carriers/non-carriers Carrier = 1/2 x 1/25 = 1/50 Non-Carrier = 1-1/50 = 49/50 Conditional Risk – what is the patients risk of being normal? .Both have already had 2 healthy children = healthy children = risk Carrier: 3/4 [child 1] x 3/4 [child 2] = 9/16 1/4 = chance of having homozygote recessive 3/4 = chance of being heterozygote or homozygote dominant = unaffected Non-Carrier = 4/4 .risk has decrease – originally 1/2.
if sex is unknown: 3/26 x ½ = 3/52 .risk of Amelia’s son being a isolated case (1/3) Conditional Risk 1 – what is the patients risk of being normal? .70% of DMD carriers show normal CPK levels Carrier: 30% = 3/10 Non-Carrier = 10/10 Conditional Risk 2 – what is the patients risk of being normal? Carrier: 1/2 .Prior Risk – risk that Amelia is a carrier/non-carrier Carrier = 2/3 Non-Carrier = 1/3 .for having a healthy boy Non-Carrier = 2/2 Joint Risk – (Prior Risk) x (Conditional Risk) Carrier = (2/3) x (3/10) x (1/2) = 6/60 Non-Carrier = (1/3) x (10/10) x (2/2) = 20/60 Posterior Risk – (Joint Risk)/(Sum of Joint Probabilities) Carrier = (6/60)/(6/60 + 20/60) = (6/60)/(26/60) = 6/60 x 60/26 = 6/26 Non-Carrier = (20/60)/(6/60 + 20/60) = (20/60)/(26/60) = 20/60 x 60/26 = 20/26 Amelia’s Risk of being carriers = 6/26 = 1/13 Amelia’s Risk of being having a child with Huntington’s Disease 1/13 [risk of being a carrier] x 1/2 [passing on bad allele] = 3/26 .
Methylation – X Inactivation Specific Transcripts (XIST) → inactivation .Pseudo-autosomal region – gene in that remains active and escape XIST inactivation .distal short arm regions on X and Y chromosomes . the other is inactivated .SRY is proximal to PAR1 in Y specific region .XIST is only expressed in inactivated chromosome → spread inactivation methylation signal .ex: factor VIII . SHOX gene → all in greater amounts in women 2) X inactivation occurs early in embryogenesis 3) Choice of inactivation is random and independent in each cell 4) Inactivation is irreversible and all descendents will have the same X inactivated Manifesting Heterozygotes – A woman is a mosaic of clones with maternal or paternal X’s .Dosage Compensation – “Balancing Out” – all X’s in excess of one are inactivated in females → male and females expresses similar doses of most genes on the X chromosome .ex: inactivate abnormal X more often than normal X to ensure survival X Inactivation Center (XIC) – where inactivation begins → spread to short arm and rest of long arm Pseudoautosomal Region (PAR) .Unequal recombination → XX males (SRY) + XY females (no SRY) 2) Explain the principle of X inactivation X Inactivation: Molecular Aspects . XIC.skewed X inactivation .Xp gene > Xq gene .exception: steroid sulphatase.ex: Calico cat – mosaic of black and orange due to X-inactivation Skewed X (Non-Random) Inactivation → not 50/50 inactivation .contain highly similar DNA sequences → allow for crossing-over to take place between X and Y PARs ***Recombination is higher in females than males → genetic map in female is longer than male . PAR region Lyon Hypothesis 1) A normal female will only have one X active.derivative X contains important genes due to translocation and needs to be expressed Unbalanced Translocation → inactive derivative X .1) Describe the important features of the X chromosome.deletions of Xp → more severe phenotype 3) Explain the consequences of X autosome translocations X Autosome Translocation Balanced Translocation → inactive normal X .X Inactivation Center (XIC) – where inactivation begins → spread to short arm and rest of long arm .Not all the X is inactivated if all X chromosome were inactivated → women would all be Turner’s Syndrome!! .Barr Bodies – inactive X’s seen in the non-dividing cell .
Multiplex PCR .Treatment objective = slow down disease progression and optimize cardiac/pulmonary function 5) Explain the basis of DMD expression in females X autosome translocation .DMD will involve heart muscle and respiratory system → death (age 18) Testing .Reciprocal Balance Translocations . walking. and skeletal muscle along with brain neurons . climbing stairs (Gower’s maneuvers/sign) .X-linked progressive myopathy → muscle degeneration . miscarriages.Derivative (der) – abnormal chromosome .Creatine Phosphokinase – elevated 10-20 times → indicate muscle damage .1/3 of DMD are due to new mutations *Becker Muscular Dystrophy (BMD) – allelic mutation → frame-shift mutations → shorter dystrophin protein Clinical Features Onset: childhood . cardiac.carriers are usually phenotypically normal but have reproductive problems → infertility. sitting.Linkage Analysis Treatment: .difficulty standings. point mutations .pseudohypertrophy of calf muscles . molecular and clinical features of Duchenne muscular dystrophy Duchenne Muscular Dystrophy (DMD) .No cure . children w/abnormal phenotypes or unbalanced translocations .Stain for dystrophin protein Molecular Diagnosis .70% of balanced translocations are inherited .de novo mutations during Oogenesis and spermatogenesis Isolated Case – new mutation .most commonly inherited form of muscle disease (1:3500 in males) Pathogenesis: loss of dystrophin which stabilized smooth.many female carriers of a balanced X-autosome translocation are infertile 4) Explain the genetic basis.reciprocal translocations are unique to a family . insertions.Dystrophin gene – large gene (3-78 exons) → high mutation rate → allelic heterogeneity .exchange of genetic information between non-homologous chromosomes .exchange of genetic information between homologous chromosomes at different sites .Allelic Heterogeneity – multiple types of mutations (for DMD gene) 60% = large deletion 5-10% = large duplication 25-35% = small deletions.IQ one standard deviation below the mean .
ex: if X chromosome carrying DMD allele is active → female develop signs of DMD .10% of female carriers will have life-threatening cardiomyopathy .20% of female carriers will have some muscle weakness .70% of female carriers will have slightly elevated serum creatine kinase .6) Explain the principles of skewed X inactivation in relation to the expression of the DMD in females Duchenne Muscular Dystrophy Expression in Females .Age of onset + Severity depends upon degree of skewed X inactivation .
trinucleotide repeats microsatellites (triplets which have no function) Mechanism – slippage mis-pairing .Testing .congenital form rarely from paternal carrying CTG expansion Normal – 4-37 repeats – none Premutation – 38-49 repeats – none Protomutation – 50-80 repeats – asymptomatic with mild late onset (cataracts) Mutation – 200-500 repeats – associated with 3rd or 4th decade Mutation – 280-800 repeats – childhood onset Mutation – >1000 repeats – congenital .progressively earlier onset and increased severity in successive generations . [repeats] → earlier onset + increased severity 2) Examples of disorders associated with trinucleotide expansion (myotonic dystrophy. anticipation. threshold.CTG expansion 5’ end in non-coding region of dystrophy myotonic protein kinase (DMPK) .below threshold – repeat is stable in mitosis and meiosis .Gain of function .Extreme variability .Anticipation .above threshold – repeat is unstable in mitosis and meiosis Anticipation .1) Explain characteristic features of trinucleotide repeat disorders (unstable mutation.Differential expansion in maternal and paternal allele .ex: extra repeat Dynamic Mutation – mutation which changes upon transmission .disease occurs when expansion surpasses a certain threshold .expansion in increasing number of three nucleotide repeats .Maternal transmission -1:8000 – most common heritable neuromuscular disorder . Fragile X syndrome.most common type of unstable dynamic mutation .ex: Trinucleotide Repeat Disorders .ex: replication strand detaches inappropriately from template .autosomal dominant . Huntington’s Disease) Myotonic Dystrophy – CTG . gender bias for expansion of the repeat) Classical Inheritance Identical inherited mutations – mutation for a genetic disorder is stable from one generation to the other Trinucleotide Repeat Disorders – Triplet Repeat Disorders .ex: replicating strands slips from proper alignment → mis-match .Threshold > 50 repeats .greater expansion if maternally inherited → congenital form almost always maternally inherited .
prominent jaw.Median age of survival – 15-18 years .Full Mutations are mitotically unstable .1:4000 (male).EMB .Anticipation – expansion → earlier the onset .Female carriers of premutation are at risk of premature ovarian failure . age of presentation – 35-44 (25% developed after 50 years old) .Differential expansion in maternal and paternal allele .Eye exam ..Avg. large testis .Male carriers of expanded.Threshold > 200 repeats .Voluntary and Involuntary movement – chorea (90%) .Maternal transmission .FRM1 – hypermethylation → loss of function due to expansion of CGG triplet → moderate retardation (males) – IQ 30-50 → mild retardation (females) – Skewed X inactivation .Testing .autosomal dominant .behavioral disturbances .Cannot release handshake Fragile X Syndrome – CGG/GCC .Serum creatine kinase .Somatic Mosaicism – patients can have a mixture of cells ranging from premutation to full mutation Normal – 6-44 repeats – normal Gray Zone – 45-58 repeats Premutation – 59-200 repeats – normal intellect Full Mutation – > 200 repeats **risk of expansion from premutation to full mutation increases with length of premutation .Paternal transmission .Southern Blot Analysis Huntington Disease – CAG .X-linked recessive .CAG repeat in exon 1 coding for polyglutamine → toxic gene product . large ear.Post-Puberty – long head.Onset: childhood . but unmethylated premuation at risk of Tremor/Ataxia Syndrome (FXTAS) .Threshold > 40 repeats .affect mostly men over 50 years old .cognitive abnormalities .Loss of function .Pre-Puberty – large head .Gain of function . 1:8000 (females) – leading cause of inherited mental retardation .
expansion > 36 repeats from paternal transmission (more common) Normal – < 26 Mutable – 27-35 – all patients inherit this allele from their father Reduce Penetrance – 36-39 Huntington Disease – > 40 .Anticipation ..
occur during gametogenesis → maintained through embryogenesis and in somatic tissue . complete moles) Hydatidiform Moles .Cause: dispermy or endoreduplication .rarely survives to term Partial Hydatidiform Mole .genomic imprinting is erased and reset in the germ line cells for the next generation 2) Know some evidence of imprinting in humans (partial vs.differential expression of alleles depending on parental origin → homologous chromosomes are not expression equally → diseases can result whether a gene is inherited from maternal or paternal origins → methylation – main mechanism by which expression is modified .Cause: fertilization of an empty ovum by 2 sperm or single sperm undergoes endoreduplication .68 chromosomes (46 from father + 23 mother) .molar pregnancy derived from chorionic villi → burrow into uterus .Risk: degeneration into choriocarcinoma (15-20%) .46 XX (85%) . Embryoblast .Maternal derived genes essential for embryo development .no fetus present Differential Expression Trophoblast vs.Imprinting Control Regions (ICR) – regulation of imprinting .1) Understand the basis of genomic imprinting Genomic Imprinting .Epigenetic – heritable changes to gene expression that are not due to difference in genetic code .46 XY (15%) .fetus present but not viable Complete Hydatidiform Mole .Paternal derived genes essential for trophoblast development .Maternal nuclear genes: embryo will develop but trophoblast development is poor Conclusion: .46 chromosomes (from father) .Differentially Methylated Regions (DMR) – genes know to be imprinted .Paternal nuclear genes: embryo fails to develop but trophoblast development proceeds unimpaired .
Severe learning disabilities .Epilepsy .Phenotypical Features .Infantile feeding difficulties .Non-disjunction @ Meiosis II → uniparental isodisomy (both chromosomes are the same and maternal) .Mechanisms 1) Interstitial paternal deletion at long arm of chromosome 15 (70-75%) .Recurrence Risk: 50% .Mechanisms 1) Interstitial maternal deletion at long arm of chromosome 15 (70-75%) .Recurrence Risk: <1% 2) Maternal Uniparental Disomy (25%) → functionally equivalent to a paternal deletion .Non-disjunction @ Meiosis I → uniparental heterodisomy (both chromosomes are different but maternal) .15q11-q13 .ex: mutation of Imprinting Control Region → fail to switch maternal imprints to paternal imprints → fail to express active gene (paternal gene) .Dysmorphism – abnormal morphologic development .Hypotonia .most often leads to PWS *Prader-Willi Syndrome (PWS) .Cognitive impairment .ex: parent with balance translocation → child with unbalance karyotype 4) Imprinting Failure (2%) .Recurrence Risk: <1% 3) Chromosomal Abnormality (1%) .Treat: Growth Hormone replacement to normalize height and improve lean body mass .Childhood hyperphagia and obesity .Testing: FISH .Unsteady gait .associated with advance maternal age → Maternal heterodisomy .3) Understand the clinical and molecular basis of and the mechanism of uniparental disomy (UPD) in Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS) Uniparental Disomy (UPD) .Phenotypical Features .“Happy face” .Sterility .deletion cause: illegitimate recombination .Risk: for additional children with PWS depends on what is the molecular cause of the PWS *Angelman Syndrome (AS) .
.Parental isodisomy – monosomy rescue .ex: mutation of Imprinting Control Region → fail to switch maternal imprints to paternal imprints → fail to express active gene (maternal gene) .Recurrence Risk: 50% .ex: parent with balance translocation → child with unbalance karyotype ***Majority of all imprinting disorders are sporadic and not familial!! .Gonadal mosaicism – some eggs may contain the mutation 5) Chromosomal Abnormality (rare) .15q11-q13 .Recurrence Risk: <1% 2) Paternal Uniparental Disomy (5%) → functionally equivalent to a maternal deletion .Recurrence Risk: <1% 3) Point Mutation – UBE3A deletion (10%) – ubiquitin gene expressed in the brain .Recurrence Risk: 50% 4) Imprinting Failure (5%) .
Telomeres – tandem repeat sequences Genetic Distance – centiMorgan (cM) .Single Nucleotide Polymorphism (SNP) .Minisatellite – VNTR .1 cM = 1% of recombination frequency (θ = 0.Biallelic marker – RFLP genes encoding for proteins .Microsatellite – nucleotide repeats .markers should be numerous and highly polymorphic polymorphism increases probability that mating will be informative 1) How far are two loci apart? .always take the maximal value of LOD LOD-Score = Log10 x (Linkage/No Linkage) LOD > 1 = suggest two loci are linked .estimate strength b calculating LOD-score .Centromere – tandem repeat sequences .1) Understand molecule markers Locus – particular location on the chromosome (loci) Allele – particular form of a gene Genetic Markers . non-linkage? .01) .1 cM = 1 million base pairs (human) 2) Understand polymorphism Polymorphism – when multiple phenotypes exist in a population of species (ex: hair color) 3) Understand the difference between physical and genetic maps Physical Map – number of bp Genetic Map – number of recombinants 4) Understand how to determine the phase using the marker in coupling with the disease 5) Understand what is a recombinant and non-recombinant and be able to calculate (θ) from a pedigree 6) Understand the basic concept of LOD score Genetic Linkage Linked – 2 loci closely adjacent on the same chromosome are observed to be inherited together Coupling – linked alleles on the same chromosome Repulsion – alleles on opposite chromosomes Linkage Phase – positioning of linked alleles in coupling and repulsion Haplotype – groups of alleles that are coupled .estimate distance by recombination frequency (θ) θ = (# recombinants)/(Total # of offspring) 2) How strong is the evidence for linkage vs.
if genes responsible for a disease is unknown or you cannot identify known mutations Linkage Disequilibrium – significant deviation (more than by chance) from expected values Linkage Equilibrium – haplotype has frequency of 0.2 to give you the disease .Do not always know the phase!! .95% affected .25 in a population Examples: θ = 0.ex: cannot establish phase in 2 generations = not enough information When Use Linkage? .05 – chance of recombination (mutation that changes what is expected) .LOD < 1 = suggests two loci are unlinked LOD + 3 and above = proof of linkage LOD – 2 and below = not linked 7) Apply genetic linkage in autosomal dominant/recessive and X-linked conditions Possible Problems .5% normal .you would expect 1.
95% normal .θ = 0.5% affected .you would expect 2. 2 not give you the disease .05 – chance of recombination (mutation that changes what is expected) .
hormones) .Liquor folliculi = exudate of plasma (GAGs. corpus luteum. simple squamous → Filopodia penetrate zona pellucida and contact oocyte via gap junctions . steroid-binding proteins.Cortical Granules – locate beneath plasma membrane .3cm long.Zone pellucida – composed of GAG and glycoproteins . proteoglycans. ER. corpus albicans Hormonal Overview GnRH → pars distalis → LH → corpus luteum + ovulation + enhance maturation of follicle → FSH → maturation of follicle + ovulation Secondary + Mature Follicle → Estrogen Corpus Luteum → Progesterone → receptive for blastocyst (implantation) Primary Follicle .Content: blood vessels and connective tissue Cortical Region (outer) .Annulate Lamellae – profiles of nuclear envelope (unknown function) .Balbiani Body – concentrated collection of Golgi membranes.secrete OMI → arrest development of primary oocyte (diplotene – prophase I) Medullary Region (inner) .Granulosa cells have FSH receptors → [Granulosa cells] + intracellular spaces + [LH receptors] .Primary Oocyte (30μm) .Activin (primary oocyte) → proliferation of follicular layer → Granulosa layer → stimulate FSH release .characterized by fluid-filled cavities . 1cm thick.Follicular (granulosa) cells surround follicle.Content: ovarian follicles.bursts → release of organelles which multiply in number . mitochondria.give rise to follicular cells .Ovary .enzymes alter plasma membrane → prevent second fertilization Growth Primary Follicle – not dependent upon FSH 1) Primordial follicle . and lysosomes . on basal lamina.Granulosa layer not vascularized Secondary Follicle .Theca folliculi – stomal connective tissue outside basal lamina 2) Unilaminar Primary Follicle – Follicular (granulosa) cells – simple cuboidal 3) Multilaminar Primary Follicle – Follicular (granulosa) cells – stratified cuboidal .large nucleus – 1 or more nucleoli + euchromatin .3cm wide Tunica Albuginea – dense connective tissue – poorly vascularized Germinal Epithelium – simple cuboidal . 1.
avascular region) → degeneration of stigma region → release of secondary oocyte at distal oviduct (fallopian tube) Corpus Luteum – remnant of Graafian follicle .Corpus hemorrhagicum – central blood clot .Cumulus Oophorus – granulosa cell projection of oocyte into antral space .Highly vascularized .temporary endocrine organ .removal of clot by phagocytes under high LH levels → Corpus Luteum .collagen fibers Mature Graafian (Pre-ovulatory) Follicle .secrete progesterone with some estrogen .LH receptor expression induced by FSH .proliferation of granulosa cell and liquor folliculi → single antrum space .estrogen → inhibit FSH → prevent second ovulation .progesterone → inhibit LH .Theca Folliculi Differentiates .basal lamina degenerates between granulosa layer and theca interna .Theca externa – outer layer .Surface of ovary loses blood → stigma region (blanched.highly vascularized – vessels migrate to Granulosa layer → vascularization of Granulosa layer! .Corona Radiata – innermost layer of cumulus cells that surrounds oocyte Summary 1) During Secondary and Mature follicle stage: LH → stimulate theca interna cells → secrete androstenedione (androgen) FSH → stimulate granulosa cells → convert androgen to estradiol (via aromatase) → [estrogen] 2) [estrogen] → negative feedback on FSH at pituitary gland → LH surge → resume of meiosis 1 → secondary oocyte + 1st polar body .Granulosa-Lutein cells (80%) – modified granulosa cells .pale-staining (30-50μm) ..Corpus Luteum .separated from Granulosa layer via basement membrane .many spaces for lipid droplets .smooth muscle cells .arrested at metaphase – meiosis 2 → ovulation (day 14 of 28 day cycle) → formation of corpus luteum Ovulation .Theca interna – inner layer – cuboidal cells .LH receptors → androstenedione (androgen) .
progesterone → inhibit LH .estrogen → inhibit FSH → prevent second ovulation .lasts 3-4 months .lasts 10-14 days .dark-staining (15μm) .Corpus Luteum of Menstruation .Corpus Luteum of Pregnancy .degenerated Corpus luteum if pregnancy does not occur → invade by macrophages/fibroblasts → fibrotic/ceasing of function (Corpus Albicans) .Theca-Lutein cells (20%) – modified theca interna cells ..all FSH-dependent follicles → atresia .Human Chorionic Gonadotropin (hCG) – secreted by syncytiotrophoblast Summary 1) Pulsatile release of GnRH every 90 minutes from arcuate nucleus 2) Development of Follicles independent of FSH 3) Activin stimulates release of FSH → proliferation/stimulation of granulosa cells 4) During Secondary and Mature follicle stage: LH → stimulate theca interna cells → secrete androstenedione (androgen) FSH → stimulate granulosa cells → convert androgen to estradiol (via aromatase) → [estrogen] 5) [estrogen] → negative feedback on FSH at pituitary gland → LH surge → resume of meiosis 1 → secondary oocyte (arrested at metaphase – meiosis 2) → ovulation (day 14 of 28 day cycle) → formation of corpus luteum 6) Corpus Luteum .secrete progesterone with some estrogen .progesterone → inhibit LH .estrogen + inhibin→ inhibit FSH → prevent second ovulation .
Muscularis .beat towards uterus Uterus (Fundus and Body) Parts: Fundus.secrete nutritive material for ovum and facilitate capacitation 2) Ciliated columnar cells .Anterior Body of Uterus = adventitia Cervix .Epithelium: 1) Non-ciliated columnar Peg or secretory cells .Vascularized – spiral arteries → rich network of capillaries + blood-filled sinusoids Basalis – narrow layer below functionalis layer . Cervix Endometrium (inner) Functionalis layer – thick superficial layer sloughed off during menstruation .Fundus + Posterior Body of Uterus = Serosa .Serosa – composed from mesothelium . Body.Regenerative layer → regenerate sloughed-off funcionalis layer (glands and connective tissue) .Oviducts (Fallopian/Uterine Tube) .muscle amount diminished and is replaced by fibrous connective tissue as you approach cervix → cervix composed of DCT w/elastic fibers and scattered smooth muscle cells .Vascularized: straight arteries (via arcuate arteries in myometrium) Myometrium .Lamina Propria .richly vascularized Infundibulum – with fimbriae Ampulla – where fertilization occurs Isthmus – narrow portion Intramural region – opening into uterus Layers .outer longitudinal smooth muscle .Mucosa – extensive folds that project into lumen .muscles hypertrophy during pregnancy along with connective tissue (50 → 500μm) Perimetrium .Lamina Propria: tubular glands extending from basalis layer .inner circular smooth muscle .Muscular Layers (3) – smooth muscle Inner Longitudinal Outer Circular (Statum Vasculare) – highly vascularized – arcuate arteries Outer longitudinal .Epithelium: simple columnar epithelium – non-cilitated columnar secretory + ciliated columnar .Epithelium: simple columnar epithelium – mucus secreting → Transformational Zone – transform into stratified squamous non-keratinized epithelium .
Relaxin → destroy collagen → cervical expansion (prior to parturition) .Nabothian Cysts – obstructed endocervical glands Menstrual Cycle Ischemic Phase – sometimes present depending on textbook!! .Spiral arteries permanently constrict 2 days before day 1 Menstrual (Bleeding) Phase – Day 1 – Day 4 .Epithelium – non-keratinized stratified squamous epithelium (200μm) .T.Cervical Glands – simple columnar epithelium – cervical glands located below epithelium Ovulation → secrete serous fluid – allow sperm to enter Normally → viscous secretions → plug at cervix (via progesterone) .Functionalis layer is sloughed-off 35 mL blood loss Proliferative (Follicular) Phase Day 4 – Day 14 .Renewal of epithelium of endometrium initiated by estrogen .highly vascularized .Implantation .***development of cancer often starts in transformational zone ***epithelium similar to esophagus but no esophageal glands .Estrogen → stimulate synthesis and storage of glycogen .Langerhan cells .Lamina Propria .Occurs during same time ovarian follicles are developing Secretory (Luteal) Phase .Functionalis layer continues to grow (5-6 mm) influenced by progesterone → increased vascularity → edema → accumulation of glycogen secretions → endometrial glands become convoluted and branched .Stromal cells (C.Spiral arteries permanently constrict 2 days before day 1→ ischemia/necrosis + dilation of spiral arteries → bursting of spiral arteries → discharge of blood that removes functionalis layer .influenced by progesterone Vagina Mucosa . surrounding glands) → Decidual cells – pale and glycogen rich .No glands – lubrication from glands of cervix (differentiate from esophagus) .Mucosal Lining is not sloughed-off during menstruation .glycogen converted by bacteria to lactic acid as cells are sloughed-off → pH → anti-microbial .functionalis layer 2-3 mm thick .Loose Connective Tissue → allow for expansion .
Colostrum – protein-rich fluid.Lobules → Lobes → Lactiferous duct → Lactiferous sinus .Sphincter of striated muscle at external opening of vagina Adventitia – fibroelastic connective tissue Mammary Glands . lactose.Outer Longitudinal smooth muscle – intermingles with inner circular layer .Inner Circular smooth muscle .Lactiferous Duct/Sinus: stratified cuboidal epithelium Lactating (active) .Milk Content: protein.Muscularis .Epithelium .sparse undeveloped alveoli + inactive duct elements .alveoli surround by myoepithelial cells – influenced by oxytocin → milk ejection . antibodies.Milk – replaces colostrums a few days after birth – production via prolactin . lipids.Tubuloalveolar glands .Protein Secretion: Merocrine (exocytosis) Resting (Non-secreting) .Duct: simple columnar epithelium . first milk released by mothers .Lactiferous Sinus – dilated portion of lactiferous duct which stores milk . lymphocytes. fat-soluble vitamins .Lipid Secretion: Apocrine (membrane budding) .developed alveoli + hypertrophy of breast via estrogen and progesterone . monocytes.
Growth of chorionic villi posteriorly → compression and degeneration of decidua capsularis → smooth chorion (chorion laeve) – avascular bare area .divide placenta into incomplete cotyledons (compartments) .prevent adherence . yolk sac.intervillous space lined by syncytiotrophoblast ( derived from synctiotrophoblasts) Amniochorionic Membrane – fusion of amnion and smooth chorion .4th month – decidua basalis replaced by frondosum Fetomaternal Junction . Use diagrams to show features of placental structure and function The Placenta . chorion.Fetomaternal organ Fetal Portion – chorion frondosum (villous chorion) Maternal Portion – decidua basalis (functionalis layer of endometrium) Decidua .fluid replaces every 3 hours – fetus swallows its own amniotic fluid 2) Describe the development of the placenta.Cytoprophoblastic shell – attach villous chorion to decidua basalis → anchor to chorionic sac .Placenta Septa – decidua basalis that erodes into intervillous spaces → wedge shaped septa .allows for fetal movement .Amniotic fluid .Decidua capsularis – overlies conceptus .adhere to decidua parietalis → ruptures during labor → amniotic fluid escape through cervix and vagina 3) Illustrate the placental membrane barrier and discuss the transfer of materials between fetal and maternal blood Circulation of Placenta .endometrial vessels pass through shell → open in intervillous (lacunar) spaces via gap junctions .absorb jolts .Growth of chorionic villi anteriorly → growth into decidua basalis → Chorion frondosum (villous chorion) .rapid enlargement → envelopment of connecting stalk and yolk sac → primitive umbillical cord .Decidua parietalis – remaining parts of decidua Tertiary Villus – filled with capillaries and connective tissue Chorionic Villi .1) Use diagrams to show the fetal membranes and discuss the fate of each (amnion. and allantois) Primitive Umbillical Cord 1) Connecting Stalk – Allantois + Umbillical Vessels 2) Yolk Stalk – Vitelline Duct + vessels 3) Canal – connect intraembryonic and extraembryonic cavities Amniotic Cavity .Decidua basalis – forms maternal portion of placenta .
Progesterone – maintain corpus luteum . fatty acids..maternal antibodies (week 14) – IgG → passive immunity .Syncytiotrophoblast – proteins and steroids . pinocytosis) .Synthesis: glycogen.Human Chorionic Gonadotropin (hCG) – maintain corpus luteum .max levels just before end of pregnancy ***Protein hormones do not cross placenta except T4.measured to determine pregnancy .Pre-week 20 – 4 layers 1) Syncytiotrophoblast 2) Cytotrophoblast 3) Connective tissue in villous core – extraembryonic mesoderm 4) Endothelium of fetal capillaries .Thyrotropin (hCT) .Post-week 20 – 2 layers → faster exchange 1) Syncytiotrophoblast 2) Endothelium of fetal capillaries 4) List the main activities of the placenta and explain their role in maintaining pregnancy and promoting embryonic development Function of Placenta 1) Metabolism . T3 and Unconjugated steroids ***Drugs can cross placenta via simple diffusion 5) Discuss the effects of drugs. cholesterol 2) Transport (simple diffusion.Corticotropin (hCACTH) .Endometrial veins – return blood to maternal circulation Fetal Circulation .Placental Membrane/Barrier – separates maternal and fetal blood → no mixing of blood!! . active transport. electrolytes . and microorganisms that can cross the placental barrier *Alcohol *Organic Mercury *Thalidomide *Diethystilbestrol – synthetic estrogen – cross placenta → carcinoma of vagina + abnormal testis *Treponema pallidum – syphilis – cross placenta *Toxoplasma gondii – toxoplasmosis – cross placenta → damage to eye and brain .Human Chorionic Somatomammotropin (hCS) – give fetus priority on maternal glucose . viruses.gases. nutrients.newborns reach adult levels at age 3 3) Endocrine Secretion .Estriol – stimulate uterine growth and development of mammary glands .Arterio-Capillary-Venous System – brings fetal venous blood close to maternal blood . facilitated diffusion.blood flows slowly over branch villi → gas/nutrient/metabolic product exchange .Endometrial arteries – maternal blood flows into intervillous spaces toward chorionic plate .
6) Use diagrams to show the gross and microscopic features of the placenta and umbilical cord 7) Discuss the embryological basis on twins Dizygotic Twins – fraternal twins – 2 eggs + 2 sperm Monozygotic Twins – paternal (identical) twins – 1 eggs + 1 sperm .
1. 3. 21.invisible nasal bone indicates abnormality .short stature .widely-spaced nipples .primary (maternal) → trisomy .“webbed” neck .severe defects → spontaneous abortion (99% occurrence) . and rarely others Ultrasound Findings: Nuchal translucency + heart/renal defects + cystic hygroma . 3.always have one repeat unit that is single stranded at the tip of the 3’ strand .mutation in 18 and 13 → more severe .defect in paternal meiosis or mitotic error Complication: Heart Defect (30%). Y are viable .2 cells with 1 of 1 type → normal .1 cell with 2 of 1 type → trisomy (ex: 1. 3) .Telomere Structure . 3. hypertension.2 cells with 1 of each type → trisomy (ex: 1.infertile Incidence: 1/2500 to 1/5000 females .trisomy 16 is most common → spontaneous abortion .Telomere repeats sequence = AGGGTT = GGTTAG = TTAGGG .1 cell with nothing → monosomy *Quantitative Marker Analysis – measure with quantitative marker and compare peaks (ex: 1.abnormally large (> 95 percentile) indicates abnormality . 7) Turner Syndrome (Monosomy X) Diagnosis: .secondary (paternal) → monosomy . 3 vs.2 cells with nothing → monosomy .99% of monosomy X die in utero Non-disjunctions – primary or secondary meiotic non-disjunctions .normal intelligence . 18.Nuchal translucency – space between soft issue of spine and skin . 3. 7) . X.size and amount of genes on chromosome determines severity .triple helix loop stabilized by proteins → protection from degradation Mosaicism – mitotic error → two cells that differ in content or expression Chimerism – inclusion of cells originating in two different zygotes Euploidy – normal chromosome count Aneuploidy – abnormal chromosome count Polyploidy – extra copies of ALL chromosomes → not viable Trisomy – excess of one chromosome → only Trisomy 13.80% of trisomy 21 die in utero Monosomy – lack of one chromosome → only Monosomy X is viable . Renal defect (30%).missing development of secondary sexual characteristic .
15% mosaics Complications: obesity.specific head. XXXX or 49. Alzheimer’s disease (APP gene) 95% = trisomy 21 3-4% = have a translocation of trisomy 21 (usually Robertsonian) . XXX) Diagnosis: .heart malformation (40%) .Gynecomastia (55%) ***Test for pituitary gonadotrophins (feedback) Incidence: 1/1000 males . learning disabilities) Incidence: 1/1000 males Down’s syndrome (Trisomy 21) Diagnosis: .social maladjustment OR .Slightly decreased IQ .mental retardation .remove gonads if virilization occurs Kleinfelter Syndrome (47.Small testis → [testosterone] .no abnormalities to slight mental deficiency . pulmonary disease Treatment: androgens → improve virilization.learning disabilities .intelligence ranges from normal to mental retardation .Increased height .Behavioral abnormalities (hyperactivity.estrogen → induce secondary sexual characteristics . XXY) Diagnosis .44% extra paternal X .Treatment: . ADD. XXXXX Incidence: 1/1000 females . hand.hypothyroidism .developmental delays .56% extra maternal X .maternal age effect XYY Diagnosis: . diabetes.aging: early senility.growth hormone → increase height . bone density but worsen gynecomastia XXX (47.mental retardation with 48. thyroid problems.infertility . feet shapes .
distinctive.Small chin .Sloping forehead .Mental retardation .Forebrain defect . cat-like cry in babies .Deafness Incidence: 1/20000 .Prominent occiput .Mental retardation .among severely retarded = 1/100 (1%) .60% are spontaneously aborted + 20% still born = 80% die in utero .Hypertonicity – clenched fingers Incidence: 1/8000 (80% females) .ex: 14-21 translocation.Eye abnormalities .Cleft lip and palate .maternal age effect Patau Syndrome (47 XX/XY + 13) – most die within first year Diagnosis: .10% chance of having offspring with Down’s syndrome *Single incidences occur – often maternal age effect *Robertsonian translocations can lead to multiple cases in a family of Down’s syndrome Edwards Syndrome (47 XX/XY + 18) – most die within first year Diagnosis: .Heart defect (88%) .ex: 14-21 translocation carrier .Polydactyly .low birth weight .deletions variable .Malformed ears .characteristic faces Incidence: 1/20000 to 1/50000 . deletions → mental retardation .Heart Defects ..failure to thrive .severe retardation .maternal age effect Cri-du-Chat Syndrome (spontaneous deletion of several genes – chromosome 5) – good survival into 30s (Italy) Diagnosis . 21-21 translocation 1% = mosaic .
polymorphic copy number variation – variation within genome concentration in normal population Chromosomes in Cancer .ABL gene is normally tyrosine kinase receptor → inhibit ABL → stop overproduction ***Diagnosis is made by finding the BCR-ABL fusion gene ..mostly spontaneous .Visible as: .map out genome and hybridize with patient DNA .reciprocal translocation of parent DiGeorge Syndrome (CATCH-22 or VeloCardioFacial Syndrome) .) .ABL – chromosome 22 .10% .Double minutes – excised cancerous regions continue to replicate on its own after removal .tyrosine kinase inhibitor (imatinib mesylate – glivec/gleevec) .accumulation of mutations → allow for faster cell replication/division . fatigue. etc. de novo translocations .hydroxyurea can alleviate symptoms .ex: non-disjunction. structural changes. night sweats → enlarged spleen → sternal tenderness (bone pain) Treatment: .Homogenously staining regions – genetically identical regions due to cancerous cell replication .must use control probe to flag desired chromosome .development problems with 3rd and 4th brachial arch → defects in aortic area of heart → hypoparathyroidism → hypocalcemia → reduced immune function (thymus hypoplasia) → increased risk of psychiatric disease *Fluorescence in situ Hybridization (FISH) .measure hybridization signal → detect variation in concentration of genome in a patient (deletions.Karyotype useful for prognosis and treatment Philadelphia Chromosome → Chronic Myelogenous Leukemia (CML) .bone marrow transplant (only cure) .BCR-ABL fusion → BCR product is now under control of an upstream ABL promoter → overproduction of WBCs (lymphocytes) → low grade fever.use chromosome paint – cannot detect inversions and small deletions *Comparative Genome Hybridization (CGH) .BCR – chromosome 9 .Aneuploidy .many have deletion in chromosome 22 .use labeled single probe – only works if you know what you’re looking for .many cancers show unstable chromosomes during later profession .
1) Explain why multifactorial traits usually show a bell-shaped phenotypic distribution Bell Curve – bell curve distribution observed in quantitative traits - Regression Towards the Mean – offspring of extreme values tend to deviate back towards the average - extreme values usually caused by unusual environmental effects are aren’t likely to be repeated 2) Define the term heritability and state its limitations of analyzing the nature-nurture problem Heritability – total variance that is caused by genes - data comes from comparing: - monozygotic vs. dizygotic twins - twins that were adopted - siblings raised together vs. siblings adopted - siblings vs. general population Concordance – values are similar – based upon relatedness (family, monozygotic vs. dizygotic twin, etc.) Correlation – value of one is associated with a change in the value or the expectation of the other Look at notes to observe graph vs. table to measure heritability 3) Make semi-quantitative “guestimate” about the heritability of some multifactorial traits based on prior knowledge or data presented Multifactorial Inheritance – a trait influenced by both genes (plural) and environmental factors Polygenic Trait – trait determined by more than one gene but no environmental factors Liability – combination of good and bad alleles + environment Threshold Trait – when liability is above a threshold value the person will have the disease Observations 1) Siblings of affected have a higher risk than the general population affected individuals in a family = risk of being affected Rule-of-Thumb Risk – for those closely related (1st degree) - risk for sibling of an affect = square root of population risk 2) Siblings of an affected person belonging to a more rarely affect sex → higher risk - if affected person belongs to a more rarely affect sex, person must have more bad alleles - since siblings share 50% of their alleles, these siblings will have higher risk 3) More severe the symptoms → more bad genes/environment → higher risk for siblings 4) Risk decreases rapidly if relationship is less close Example: Pigmentation - determined by several (>5) genes → show additive effects - show strong signatures of selection - ex: SLC24A5 in Africans vs. Europeans 4) Specify the typical effects of the number of affected relatives and of the severity of the disease in an affected relative on the risk of multifactorial disorders 5) Apply the multifactorial threshold model to predict the relative risk to first-degree relatives of patients with a sex-influenced multifactorial disorder Allele Sharing (look at notes!!)
> 50% = linkage < 50% = no linkage - Sib-Pair Analysis - only works if parents have both good and bad alleles (must be heterozygote) - chose family with at least 2 affected siblings - calculate allele sharing in each sib-pair - average all pairs - look at linkage Linkage – loci that are close enough that they segregate together through generations Association – events occur together more often than expected in a current generation Association in Genetics – a disease and a marker allele that occur together more often than expected Linkage Disequilibrium – occurrence of specific combination of alleles more frequently than expected by chance - bad allele is found together with a specific marker allele in nearly all people carrying the bad allele - only present if no crossovers happen - Association Study – look for marker frequency in affected group - Genome Wide Association Study 6) State the role of teratogens and intrauterine infections in the pathogenesis of congenital malformations 7) Describe the importance of identifiable single-gene effects in multifactorial disorders including autoimmune diseases, type 1 and 2 diabetes, Hirschsprung’s, and Alzheimer. *Hirschsprung’s Disease – “megacolon” due to failure of migration/differentiation of neural crest cells - male > females (4:1) - high heritability ( 100%) – polygenic - RET gene – implicated with dominant mutations - involved in tumors after activating mutations - involved in Hirschsprung’s Disease after inactivating mutation - involved in development and migration of neural-crest cells - Long Segmental Form - male females - mutations of coding region → complete inactivation of RET - Short Segmental Form - male > female - Multifactorial – Chromosome 3, 10, 19 - mutations in enhancer → reduced penetrance → turn down expression of RET *Diabetes Mellitus – Type 1 (IDDM) - General Population = 0.3-0.5% - Sibling of affected = 6% - Affected Father = 4-6% - Affected Mother = 1-3% - Monozygotic Twins = 30-50% → not purely genetic!! - Genetic factors 1) Allele DR3 and DR4 on MHC >95% of all IDDM patients
2) Aspartic acid in position 57 of DQ = protective against IDDM → DR3/DR4 could serve as marker to non-aspartic acid in DQ region 3) Insulin gene → HLA alleles may not be presented well enough in thymus → auto-immunity - short repeat = increased risk - long repeat = increased insulin expression in thymus → better immune tolerance - Environmental factors - Viral infections → trigger immune reaction that cross-reacts with pancreas - ex: Coxsackie B, enterovirus - anti-Coxsackie B antibodies in 39% of children with IDDM *Diabetes Mellitus – Type 2 (NIDDM) 5-10 X more common than IDDM - Sibling of Affected = 15-40% - Monozygotic Twins = 90% → high heritability (concordance) → mostly genetic!! - Genetic Factors TCF7L2 – transcription factor → insulin secretion = 1.5X risk PPAR-γ – transcription factor → adipose/glucose metabolism = 1.25X risk KCNJ11 – potassium channel → insulin secretion = 1.2X risk - Environmental Factors - Obesity; low birth weight; diet, activity, etc. *Diabetes Mellitus – Maturity-Onset Diabetes of the Young (MODY) - autosomal dominant with 80-95% penetrance - 5% of all diabetes cases - multifactorial – 7 known genes (glucokinase) - often misdiagnosed as type I - Onset: < 25 years old - often not obese - metabolic syndrome is absent Obesity - major influence of environment - high concordance - Leptin; NPY; melanocortin 4-receptor *Alzheimer’s Disease - formation of amyloid plaques and neurofibrillary tangles - Genetic Factors 1) Amyloid Precursor Protein (APP) - cleavage by -secretase → Aβ40 and Aβ42 → overproduction → amyloid plaques and neurofibrillary tangles - Presenilin-1 and Presenilin-2 - regulation of -secretase
observe multifactorial inheritance ..genetically heterogenous group . maternal conditions. needs greater amount of defective genes *Mental Retardation .Heterozygote = 3X risk 3) Interleukin-1 .APP gene located on Chromosome 21 → mutations of APP → [Aβ40 and Aβ42] . etc.involved in inflammation . nutrition.Risk Factor: high maternal age.Concordance = 79% for monozygotic twins . Minor Genes – additive effects .multifactorial .environment (drugs. low education *Schizophrenia .mutations → increased cleavage → [Aβ40 and Aβ42] 2) ApoE4 .Increased risk for sibling or children of affected female .Race .single gene disorder *Pyloric Stenosis .) .no specific genes identified *Treatment of Coronary Heart Disease and Stroke .Homozygote = 15X risk .for female to be affected.Global Developmental Delay – retardation < 5 years old .Concordance = 60-85% for monozygotic twins .genetics (chromosomal abnormalities) .overexpression of IL-1 correlated with plaque formation .Male > Females .Risk Factor: high paternal age *Bipolar Affective Disorder .higher incidence in African American and Hispanic communities (genetic or environmental) *Down’s Syndrome .test for CYP2Cp and VKORC1 before starting treatment to improve accuracy of initial drug dosage 8) Describe the major/minor gene alleles have for risk assessment in disease where they occur and state examples of each in Hirschsprung’s and Alzheimer.causes: .IQ < 70 . infection.ABCG1 gene on Chromosome 21 also suspect *Cancer – best considered multifactorial with low heritability (majority) *Congenital Malformation .multifactorial (genetic and environmental) .
observe Mendelian inheritance Additive Model – mixing of one gene between two different populations .Major Genes – act as a dominant allele which will confer risk .looks similar to selective distribution .1 phenotype dominants and is expressed more often .effects of each allele are co-dominant and have same level of influence on the trait Dominant Model – mixing of one gene between two different populations .
but proportion of homozygotes would increase 4) New mutations and selection offset each other 5) Population should be large .sibling of affected = 2/3 chance of passing on defective gene ***For X-linked recessive . State legal status of incest in related in part to these expected effects Effects of Small Interbreeding Population Autosomal Recessive: → increased frequency of homozygous affected for recessive diseases → increased selection against bad alleles (long-term effect) Multifactorial: → increased number of affected → decreased intelligence ***genetic drift may change allele frequency from one generation to the next .males have a greater chance of being affected = multiply by ½ q = incidence in males q2 = X-linked recessive (affected females) 2pq = X-linked dominant (affected females) 3) Predict the effects of inbreeding and incest on the incidence of autosomal recessive and multifactorial disorders.decreased frequency of bad alleles 6) No gene flow (migration) 2) Use Hardy-Weinberg to predict allele frequency and frequency of different genotypes for single gene disorders if the disease incidence is known Hardy-Weinberg Equation When having a number of actual people.1) State the criteria for a valid Hardy-Weinberg equation Rules: 1) Valid for population in equilibrium – allele frequency will stay the same in following generations 2) Mating must be random 3) Consanguinity (incest) – would not change allele frequencies .offset genetic drift . could alleles instead of using Hardy-Weinberg!! p2 + 2pq + q2 = 1 p2 = homozygote dominant 2pq = heterozygote frequency (carrier frequency) q2 = homozygote recessive (incidence) p = 1-q Review Semester 1 Pedigree ***In autosomal-recessive disorder .more genetic variability .
etc. etc. . founder effect. offspring.Stabilizing .Directional . etc.can only include diseases with a low mutation rate .extreme phenotypes do not perform as well → narrowing of distribution towards median . it would not really work. genetic drift.Large deletions are more likely to arise in female meiosis (maternal age effect) .one extreme of phenotypes performs better → movement of distribution towards one extreme .extremes phenotypes do well.5% of alleles (ex: first cousins. It would take 10 generations to have 25% of the population having the gene and probably many more to get it to a smaller percentage. disruptive. uncles.ex: Afrikaners (variegate Porphyria) . 5) Define the term stabilizing.ex: Old Order Amish (Ellis-van Creveld syndrome).) → 3% incidence of severe mortality and mortality Third degree Relatives = 12.) → 30% incidence of severe mortality and mortality Second degree Relatives = 25% of alleles (ex: half-siblings. assortative mating Founder Effect . parents.ex: blood pressure . Give examples of each Selection Types .ex: birds at Galapagos Islands 6) Define heterozygote advantage.ex: higher education in women . and state that the lack of effects makes negative eugenetic unethical and scientifically wrong Complete Selection – when a person does not have viable offspring Even if implemented.) → 1% incidence of severe mortality and mortality Interbreeding Coefficient – percentage of gene loci that are homozygous as a result of interbreeding 4) Describe the expected effects of negative selection of allele frequencies of autosomal recessive and dominant diseases.Disruptive . grandparents.Point Mutations increases with paternal age .isolated population which descends from a small group of people who harbor an otherwise rare mutation → increased occurrence of a otherwise rare mutation within this isolated group . but average does not do well → split into two sub-populations . and directional selection.Monozygotic Twins = share 100% of alleles First degree Relatives = 50% of alleles (ex: siblings.ex: Pingelap islanders (Achromatopsia 3) Assortative mating – actively chosen mating Heterozygote Advantage – heterozygote genotype has a higher fitness than either homozygote dominant/recessive \ 7) State the effects of paternal age on rate of point mutations Mutations .
applications. infectious disease .Analyze sperm: quality. endometriosis. or other causes of infertility Procedure: . aromatase inhibitors 2) Harvest eggs 3) Add sperm 4) Incubate 2-3 days 5) Implant 2-6 embryos .infertile husband . more common with increased age . tubal obstructions . triplets – 1.1%) Oocyte Donation: $4200 per egg . and procedures of IVF and ICSI Intravenous Fertilization (IVF) Indication: tubal disease (obstruction).1) Age-dependence on infertility and specific causes Infertility – no pregnancy after trying for a minimum of 1 year .genetic disease . applications. Y-chromosome microdeletions.Family history of donor . autoimmune.Success dependent upon age of mother or oocyte donor < 38 = 36% > 40 = 11% Risks: multiple pregnancies (twins – 22%.Carrier tests 3) Principles.peak fertility at age 22 Female Fertility – normally 20-25% change of pregnancy in 1 cycle Major Risk: multiple pregnancies 2) Principles.done in specialized clinics 1) Induce superovulation – gonadotropins. Klinefelter.implantation dependent upon age of female age = quality of egg → implantation amount age = quality of egg → implantation amount Outcome . and procedures of sperm banking and donor insemination Donor Insemination Indication .rhesus incompatibility .Prevalence: <10% of young couples. age Female: age.Cause: Males: infections.Educational/psycho-history of donor . single gene. clomiphene. polycystic ovaries.career women Procedure: sperm bank → select donor → order frozen sperm → thaw → inseminate Sperm Banks .
low sperm count .Make IVF .immotile sperm .Shotgun screening – whole-genome amplification and DNA microassays 5) Major risks of procedures for assisted reproduction . and procedures of pre-implantation genetic diagnosis Pre-Implantation Genetic Diagnosis .post-vasectomy Procedure .Cryopreservation .sperm can be frozen but insemination success is less than with fresh sperm .Single-gene disorder: PCR .Aneuploidy: FISH .freezing can damage living cells (ex: osmotic stress. applications.Remove 1-2 cells for testing .sperm is immobilized → sucked into needle → injected directly into egg cytoplasm during IVF Risk: Slight increased risk of Beckwith-Wiedeman (overweight fetus) Slight increased risk of Angelman syndromes (imprinting error) 4) Principles.poor sperm quality .oocytes are difficult to freeze Technique: 1) Add antifreeze 2) Rapid freezing Intracytoplasmic Sperm Injection (ICSI) Indication: .egg can be frozen without major risks .Grow embryo to 8-cell stage . ice crystals piercing membranes) .only possible with small tissue sample (organs or bodies are impossible) .diagnosis of genetic diseases in early embryo Procedure .
oral formulations are hepatotoxic .fatty acid-esterification → increase lipid solubility .Replacement therapy in male hypogonadism .used in conjunction with Leuprolide → prevent disease flare at initiation of leuprolide Finasteride – 5-Reductase Inhibitor .depot IM injection to bypass enterohepatic circulation 17-Alkylated Androgens .Use: androgen-dependent hyperplasia (BPH) → blocks formation of androgen that supports prostate growth and hyperplasia Gonadotropin-Related Drugs Leuprolide – GnRH Agonist . possible skin irritation Testosterone 1) Begin with low dose → stimulate skeletal growth and secondary sex characteristic → avoid premature epiphyseal closure 2) Gradual increase until maturity achieved 3) Establish lifelong regimen Testosterone Enanthate – Testosterone Ester .non-scrotal patch .induce fertility with gonadotropins .GnRH receptor antagonist → [androgens] .Androgens .“chemical castration” .establish normal puberty and then support male secondary sex characteristics .lipid solubility → depot preparation – few complications → gel preparation – applied daily with attention to bathing and possible contact with others → patch preparations – must be changed once or twice daily.Not effective for primary hypogonadism (problems with testes) .oral formulation of androgens .hepatotoxic Drugs to Block Androgen Activity Flutamide – Receptor Inhibitors .scrotal skin – high rate of DHT conversion → [DHT] → BPH risk .use in conjunction with flutamide Abarelix – GnRH Antagonist .down regulate GnRH receptor → [androgens] .high rate of hepatic metabolism → insufficient testosterone levels .“chemical castration” .Not effectively administered orally .not as effective as leuprolide .
rapid first-pass metabolism → poor bioavailability = give in high doses Norgestrel/Levonorgestrel.Smokers > 35 years old contraindicated Estrogens Estradiol (17β-estradiol) . Norethindrone – 19-Nortestosterone Derivatives .Bromocriptine – dopamine agonist .exogenous gonadotropins .suppress endogenous gonadotropins with GnRH .administer exogenous gonadotropins Ovarian Clomiphene – anti-estrogen .not currently available .micronized for sufficient surface area for rapid absorption → highly absorbed through epithelial surfaces → cleared rapidly after oral administration Mestranol – metabolized to ethinyl estradiol Ethinyl Estradiol – more resistant to hepatic degradation Progestins .obesity → risk of venous thrombosis Combined Oral Contraceptives .smoking → hypercoagulability .inhibit prolactin → treat hyperprolactinemia Treatments of Infertility Hypothalamic GnRH .high doses of estrogen → clotting factors .lower incidence of multiple birth Pituitary Menotropins (FSH + LH) hCG (LH) FSH LH .block negative feedback that decreases hypothalamic pulsatility → [LD] + [FSH] Contraception Adverse Effects .administration – pump → mimic in vivo pulsatility .
decidualized endometrium → non-receptive to implantation .decreased fallopian tube motility .some androgenic actions Desogestrel – Gonanes .good oral activity .mineralcorticoid antagonist Selective Progesterone Receptor Modulator Mifepristone Ulipristal .newer 19-Nortestosterone Derivative .Use up to 5 days after intercourse .effects closer to progesterone Drospirenone – Spironolactone Derivative ..less androgenic activity Medroxyprogesterone – C-21 .emergency contraception .thicken cervical mucus → prevent sperm travel .suppression of LH → prevent ovulation .Best tolerated emergency contraceptive Progestin Actions: .C-21 derivative .
Superior (Internal) Venous plexus .Factors: Pregnancy.Pectinate line Upper . Supra-levator.Location: Transsphincteric.Treat: fistulotomy *Episiotomy – mediolateral cut to avoid tearing into external anal sphincter . → drain to portal system Lower . Extrasprincteric .Inferior (External) Venous plexus . Portal Hypertension *External Hemorrhoids – dilation of external rectal venous plexus – puritis (itching) and painful . infection of anal crypts .Somatic motor/sensory innervation .Inferior Mesenteric Artery → superior rectal a.Superficial inguinal lymph nodes .filled with fat .Visceral motor/sensory innervation . episiotomy *Internal Hemorrhoids – dilation of internal rectal veins – painless .Internal pudendal artery/vein – inferior rectal artery/vein . Intersphincteric. perianal abscess. → inferior rectal a.Anal Crypt – ducts of glands .Ischiorectal (Ischioanal) Fossa 1) Rectum.1) Be able to define pelvis. perineum. infection of anal crypts . anal and urogenital triangles Anal Triangle . → internal pudendal a.if untreated → infection → abscess *Perianal Abscesses – collection of pus outside the anus . anorectal incontinence. . Portal Hypertension *Anal Fissures – mechanical tear in squamous epithelial mucosa of anal canal . hemorrhoids.Cause: Infection of anal fissures.Anterior recess – extension into urogenital triangle . Suprasphincteric.infections of glands → spreading into ischioanal fossa . → drain to caval system 2) Understand the structures of the pelvic floor Pelvic Diaphragm = obturator internus + levator ani Urogenital Diaphragm = perineal membrane 3) Be able to place the ischioanal fossa and its contents 4) Clinical relevance: anal fissure.Location: Intersphincteric.Internal iliac lymph nodes .superior to perineal membrane and inferior to levator ani Rectum .Internal Iliac a.supportive packing . Ischiorectal.Cause: Infection of anal fissures. Constipation. Perianal .Treat: surgical drainage *Anorectal Fistulas – abnormal communication between anus and perianal skin .Factors: Pregnancy. anal canal 2) Pudendal Canal .Pudendal nerve – inferior rectal n. Constipation.can be compressed or pushed for distention of fetus and feces .
1) Describe the bones.fibers travel out of LSF → attach to greater trochanter .ASIS/AIIS .Ischial spine .Pubic Symphysis – cartilaginous joint . and any important fascia Muscles Related to the Pelvic Diaphragm Pubic Diaphragm’s Wall Piriformis – lateral rotation .PSIS/PIIS .Arcuate Line Sacrum . ligaments. apertures.forms lateral wall of pelvic diaphragm + lateral wall of perineum .Sacral Promontory Coccyx Greater Pelvis = False Pelvis = Pelvis Major Lesser Pelvis = True Pelvis = Pelvis Minor Pelvic Inlet – divide greater and lesser pelvis Ligaments Sacrotuberous – GSF – Sacrospinous + Sacrum Sacrospinous – LSF – Sacrospinous + Sacrotuberous 2) Why are the foramina of the pelvis important? Especially the greater and lesser sciatic foramina? 3) Understand the anatomical orientation of the pelvic girdle and the differences between the pelvic inlet and pelvic outlet and the clinical important ***Anatomical Position – pelvis at an angle where ASIS and pubic symphysis are one a vertical plane *Diagonal Conjugate – obstetric measurement of AP diameter of pelvic inlet (from sacral promontory to pubis) 4) Know the muscles related to the pelvic diaphragm.Greater Sciatic Notch .Lumbar-sacral joint . their orientations.Iliococcygeus .fibers travel out of GSF → attach to greater trochanter Obturator Internus – lateral rotation .Lesser Sciatic Notch .tendinous arch – thickening and lateral attachment site for levator ani Pubic Diaphragm Coccygeus Levator Ani – attach to tendinous arch (lateral) and anococcygeal ligament (medial) . and joints that compose the pelvic girdle Osteology Coxal (Hip) Bone .Ischial Tuberosity .form posterior wall of pelvic diaphragm .Sacroiliac Joint – synovial joint .Anterior Sacral Foramina .
Vessels .runs on wall of obturator internus → pudendal canal → into anal triangle . S3.Pudendal Nerve (S2.Anterior Recess – communication with urogenital triangle (deep perineal pouch) .potential space superior to perineal membrane .Perineal Body – collagenous structure that serves as an attachment to many muscles .Pubococcygeus . S4) – lies on lateral wall in pudendal canal with pudendal vessels .Ischioanal Fossa ..Labia minor .Pudendal Nerve (S2.descends and runs laterally to Sacrospinous ligament → LSF . 7) Why is the perineal body important? Why is an episiotomy? . S3. → Inferior Rectal a. S4) Urogenital Triangle 6) Describe the origination. course.Branches .Inferior Rectal Nerve .Puborectalis 5) Be familiar with the depth of the perineum and the two triangles that compose the perineum. and termination of the pudendal nerve .Pathway .Labia major .Internal Pudendal a.filled with adipose tissue – pack and provide support to rectal structures . Understand how the ischioanal fossa relates to the urogenital triangle and pelvic diaphragm Perineum – diamond-shape structure containing two anatomical triangles – triangles are 90° to each other Anal Triangle .exits lumbar-sacral plexus → GSF .commonly torn during child birth *Episiotomy – mediolateral cut to avoid tearing into external anal sphincter 8) Know the perineum is composed of three pouches/spaces Urogenital Triangle 1) Inferior Fascia of Pelvic Diaphragm 2) Deep Perineal Pouch – pouch – communication with anterior recess of ischioanal fossa 3) Perineal Membrane 4) Superficial Perineal Pouch – pouch 5) Colles’ Fascia 6) Superficial Fascia – pouch 7) Skin 9) Know the contents of the three pouches for both male and females Urogenital Triangle (Female) Skin Superficial Fascia .
Superficial Transverse Perineal .Bulb of Vestibule Musculature .Bulbospongiosus .Perineal Body – collagenous structure that serves as an attachment to many muscles .Ischiocavernosus . Colles’ Fascia Superficial Perineal Pouch Erectile Bodies .Bulbospongiosus Perineal Membrane Deep Perineal Pouch Bulbourethral gland External urethral sphincter Deep Transverse Perineal Membranous urethra Dorsal Nerve of Penis Inferior Fascia of Pelvic Diaphragm .Layers of scrotum + Testis.Corpus Spongiosum bulb of penis → Glans Penis Buck’s Fascia Musculature ..Corpus Cavernosa 2 crus .Ischiocavernosus .Superficial Transverse Perineal .Round Ligament of Uterus Colles' Fascia Superficial Perineal Pouch Vestibular (Bartholin’s) Gland – secretion of fluids during sexual arousal Paraurethral (Skene’s) Glands – remnants of prostate gland Erectile Bodies: .commonly torn during child birth Perineal Membrane Deep Perineal Pouch – communication with anterior recess of ischioanal fossa Urethral Sphincter Deep Transverse Perineal Dorsal Nerve of Clitoris Inferior Fascia of Pelvic Diaphragm Urogenital Triangle (Male) Skin Superficial Fascia .Vestibule .Clitoris . Ductus Deferens. etc. Epididymis.
Deep Dorsal Vein → Prostatic Venous Plexus .10) Understand the innervation and vasculature of the perineum Innervation .Superficial Inguinal Nodes – scrotum. glans clitoris.Deep Inguinal Nodes – glans penis.External Oblique → External spermatic fascia → Buck’s fascia (male) → Fascia lata 2) Superficial Fascia . S4) → Inferior Rectal nerve (main) → Perineal Nerve → Dorsal Nerve of Clitoris/Penis *Pudendal Nerve Block – palpate ischial spine Vasculature (Arterial) . distal end of vagina . labia minor.Internal Iliac Nodes – deep parts of perineum . labia major. distal end of vagina . S3) . Lymphatics .Superficial Dorsal Vein → Superficial External Pudendal v.Femoral Artery – superficial → Superficial External Pudendal Artery → Deep External Pudendal Artery .Subcutaneous Fatty Layer – derived from Camper’s Fascia .Pudendal Nerve (S2. S3.Deep Membranous – derived from Scarpa’s Fascia – fuse with fascia lata → Colles’ Fascia → Dartos Fascia (male) .Ilioinguinal nerve (L1) . ---DEEP----------------------DEEP--→ Artery to Bulb → Dorsal Artery of Clitoris/Penis → Urethral a. → Femoral v. Vasculature (Venous) – mostly follows arteries Exceptions: . superficial tissue of penis/clitoris 11) Know the fascial layers and their clinical importance Fascia 1) Deep Fascia . → Perineal a. glans clitoris.External Iliac Nodes – glans penis.Internal Pudendal Artery (main) → Inferior Rectal a. labia minor.Posterior Femoral Cutaneous nerve (S2.Genital Branch of Genitofemoral nerve (L1) .
fluid may pass superiorly through urogenital hiatus and distribute around prostate and bladder .ex: trauma or incorrect catheter insertion *Rupture of Membranous (Intermediate) Urethra – extravasation of urine and blood into deep perineal space .12) Know the difference between a rupture of the spongy/penile urethra and membranous urethra *Rupture of Spongy/Penile Urethra – rupture of corpus Spongiosum and spongy urethra .cause: fracture of pelvic girdle. separation of pubic symphysis and puboprostatic ligaments 13) Know the parts of the male urogenital system Male Urogenital System 1) Preprostatic Urethra 2) Prostatic Urethra 3) Intermediate (Membranous) Urethra 4) Spongy/Penile Urethra .fascia layers prevent fluid passing into the thighs and into the ischioanal fossa .
→ Artery of ductus deferens → Inferior Vesicle a.Fundus .Fimbria .Erection .Internal Os .Perineal and Pudendal nerve Male Urogenital System .Fornix .Ejaculation – prostatic urethra → external world .Detrusor Muscle Female Reproductive System .Semen – sperm + secretions Male Urogenital Vasculature Internal Iliac a.Ligaments 1) Ligament of the Ovary 2) Round Ligament of the Uterus 3) Broad Ligament of the Uterus – double layered peritoneum.Uterus . Female Urinary System .Isthmus .Emission – Testis → prostatic urethra . → Superior Gluteal a. ovary located posteriorly . → Middle Rectal a.Isthmus .Sphincter Urethrae .Autonomic Innervation → relaxation of smooth muscle → allow blood to fill sinuses .Somatic Innervation – Bulbospongiosus and Ischiocavernosus → prevent outflow of blood . → Inferior Rectal a. → Umbilical a.Ampulla . → Lateral Sacral a.External Os . → Inferior Gluteal Internal Iliac a. (posterior branch) → Iliolumbar a.Cervix .Body . (anterior branch) → Obturator a. → Superior Vesicle a.Oviduct .Infundibulum . → Internal Pudendal a.
3rd (complete) prolapses Female Urogenital Vasculature Internal Iliac a.Normal = anteflexion and anteversion . → Vaginal a. Rectum and Anal Canal Vasculature Inferior Mesenteric a. → Internal Pudendal a. → Lateral Sacral a..Peritoneum .Visceral Fascia . → Inferior Vesicle a. → Superior Vesicle a.Mesometrium 4) Suspensory Ligament of Ovary – ovarian vessels 5) Uterosacral Ligament 6) Cardinal (Transverse Cervical) Ligament – uterine vessels *Ectopic Pregnancy – pregnancy occurring outside of uterus . (Caval) Aorta → Median Sacral a.Parietal Fascia – continuous with transversalis fascia . Internal Iliac a. → Inferior Gluteal a. → Umbillical a.Flexion = angle between cervix and body of uterus . (Caval) Fascial Layers . (Caval) Internal Pudendal a. → Uterine a. → Inferior Rectal a. stretching of uterine ligaments .Mesovarium . → Superior Rectal a.Vesicouterine + Rectouterine pouch (female) Innervation . (anterior branch) → Obturator a. → Superior Gluteal a.Mesosalpinx .Rectovesicle pouch (male) .1st. (Portal) Internal Iliac a. 2nd. → Inferior Rectal a. → Middle Rectal a.90-95% occur in uterine tube Angles of Uterus and Vagina . → Middle Rectal a.Version = angle between cervix and vagina *Vaginal and Uterine Prolapse – loss of tone. (posterior branch) → Iliolumbar a.
SNS – Lesser Splanchnic (T10-T11) .PNS – Vagus .Pelvic Splanchnics – PNS (S2-S4) Sacral Splanchnics – SNS (L1-L2) Testis/Ovaries .
approximately 20 Graafian follicles are created at any one time . [NPY] [Glutamate]. External Genitalia Gender – roles assigned to them by society or themselves Biological Sex – chromosomal.Cells “turned on” to produce steroids .maintain hormonal support for the fetus until the placenta can take over .Stage 1 – Primordial follicle → primary follicle .liquor Folliculi .maintain and nurtures resident oocyte .GH → gonadal function → testosterone and estrogen → GH → IGF-1 → body growth + gonadal function + GnRH .Stage 3 – Secondary Follicle → Graafian (Mature) follicle .Puberty = 400. phenotypical Transition to Puberty Negative Feedback in Pre-Puberty (GnRH) Inhibit: GABA. Endorphins.Birth = 2 million oocyte .prepares lining of uterus to accept and implant a blastocyst .theca interna develop .000 oocytes Development of Ovarian Follicle . [Leptin] Pre-Puberty: [LH] < [FSH] Puberty: [LH] > [FSH] *** fat = [Leptin] .overweight children have greater chance of going into puberty at an earlier age Interaction between GH and LH/FSH GnRH → LH/FSH + GH . Melatonin Stimulate: Glutamate Puberty: [GABA].granulosa cells begin to secrete fluid . [Melatonin].Internal vs.Stage 2 – Primary Follicle → Multilayered state (Secondary follicle) . NPY. Testosterone.assists in fertilization . gonadal. Estrogen (E2).Most oocytes are produced by the 6th month of gestation – remain at diplotene (prophase I) .LH/FSH → gonadal function → testosterone and estrogen → GH Oogenesis Oogenesis – takes 3 menstrual cycles to mature and ovulated Ovarian Follicle .
Hypothalamo-Pituitary-Ovarian Axis FSH: initially stimulate growth of granulosa cell and estradiol synthesis Follicular Phase FSH – affect aromatase in granulosa cell → estrogen LH – affect cholesterol desmolase in theca cell → androgen Luteal Phase/Pregnancy LH – affect theca-lutein cells → androgen hCG – affect theca-lutein cells → androgen LH – affect granulosa-lutein cells → progesterone hCG – affect granulosa-lutein cells → progesterone Menstrual Cycle Follicular Phase .estrogen-mediated .Dominant Graafian follicle ovulated → retain zona pellucida and corona radiata .LH receptors appear on granulosa cells → progesterone secretion .estrogen-mediated Ovulatory Phase .LH surge → ovulation Hormonal Regulation of Oogenesis .positive feedback – estrogen → LH > FSH → drive ovulation .Dominant Graafian follicle matures → secondary oocytes (metaphase II) .one Graafian follicle is more sensitive to FSH → controls/regulates FSH → regulates estrogen to its needs only!! .Single Graafian follicle achieves dominance → regression of cohort follicles .negative feedback – kill off cohort follicles ..Stage 4 .
12-14 day lifespan unless stimulated by hCG during pregnancy .negative feedback .negative feedback – LH and FSH .driven by estradiol (estrogen) .cervical mucus ferning .FSH surge → stimulate plasminogen activator → plasmin → break down follicular wall → break down cumulus oophorus prior to ovulation Luteal Phase ..proliferation of stromal and glandular epithelium Secretory Phase .secrete progesterone .secrete steroid hormones until placenta assumes this role (during pregnancy) .driven by progesterone .inhibit uterine muscle contractions .pseudo-inflammatory → increased intrafollicular pressure .apoptosis begins by 8th day of ovulation Uterine Cycle Proliferative Phase .progesterone-mediated .progesterone indication that ovulation has occurred ***Ovum is viable for 72 hours after ovulation – fertilization is possible during this period Post-Ovulation Follicle .secrete nutrients into lumen → supply nutrients to morula prior to implantation .LH surge → prostaglandin endoperoxidase synthase (granulosa cell) .Corpus hemorrhagicum → corpus luteum .Corpus luteum → corpus albicans (no pregnancy) .estrogen levels fall 1 day before ovulation .uterine lining becomes filled with glycogen granules .increased vascularization + glandular function .
exhaustion of functional primary oocytes .causes: lack of gonads. inadequate LH/FSH secretion *Amenorrhea – loss of menstruation .LH surge . plasma [estrogen] + [progestin] → [LH]/[FSH] (loss of negative feedback) *Endometriosis – ectopically located endometrial tissue .vasospasm of vessels → ischemia/necrosis → desquamation of uterine endometrium . low body weight.often related to cessation of LH/FSH secretion .affect fallopian tube → contraction + ciliary movement → favor ovum and zygote movement .Uterus – stimulate cell proliferation + uterine tube contractility . E2 (estradiol).Breast – swelling + development of breast tissue + prepare for secretory function Menopause .max flow occurs on day 2 Estrogen and Progesterone Estrogen .Menstrual Phase progesterone from corpus lueum .first spotting is considered day 1 .response to cyclic variations of estrogen and progestions → proliferation → secretions → desquamation *Pelvic Inflammatory Disease (PID) – caused by numerous infectious organisms *Hypogonadism – lack of ovarian steroid hormones .prepare endometrium for secretory phase .kill cohort follicles .alter cervical mucus . E3 (estriol) Effects: .ex: stress. menopause .secondary sexual characteristics Progesterone Secondary Sexual Characteristics .Fallopian tube – glandular secretions . enzyme malfunction.Uterus – glandular function + uterine contraction .3 different steroids with the same effect but different affinity for the same estrogen receptor Progesterone → E1 (estrone). E3 (estriol) Testosterone → E2 (estradiol).
Gonadal . vascular. Correlate these with the sequence of the five phases in erectile process Primary Reproductive Organs – Testes Accessory Reproductive Structures – scrotum. GnRH. ducts. and progestins (include target tissue and receptor types) 8) Draw concept maps for feedback regulation of hypothalamic-pituitary-gonadal axis in males 9) Describe age-related changes in male reproductive system 10) List the sequence of four phases that constitute the sex act in males and the participation of neural. and endocrine factors in each face. FSH. 4) List major target organs or cell types of each steroid hormone and describe the effects of each 5) Define and describe the related process of spermatogenesis in males 6) Trace the development of sperm during spermatogenesis including the functions of Leydig and Sertoli cells and the interactions between these two cells 7) Describe the specific signal transduction pathways in males that mediate the actions of LH.Chromosomal . estrogen. testosterone. prostate.Phenotypical Sertoli Cells 1) Support maturation of spermatogonia 2) Growth factors 3) Androgen binding protein (ABP) 4) β-Estradiol 5) FSH receptors 6) Blood-testis barrier Leydig Cells 1) Synthesize testosterone 2) LH receptors Time Course of Male Differentiation . DHT.1) Define and describe 3 forms of sex (and 1 gender) in terms of differential embryonic development and the factors which controls this into the production of male or female tissues and organs 2) Outline the general features of biosynthesis of sex steroid hormones in males and identify the cell types in the testes that produces sex steroid hormones 3) List the primary and secondary sexual characteristics and the hormone responsible for each. Bulbourethral/Cowper’s) Defining Sex . glands (seminal vesicles.
High temperature → activity → metabolic rate → lifespan (to 1-2 days) LH effects on Leydig Cell 1) Secretion of testosterone (cAMP) .GLUT-5 – fructose transporter . Testosterone.Spermatogenesis is constant – not accelerated by androgens or gonadotropins .Acidc Medium → death of sperm → activity . Endorphins.Mitochondria .Flagellum . Estrogen (E2). FSH LH → proliferation of Leydig Cells → testosterone → appearance of primary sexual characteristics → proliferation of seminiferous tubules FSH → onset of spermatogenesis → stimulate Sertoli cell function → Spermarchy (nocturnal emission of sperm) Spermatozoa .Middle Piece .Alkaline medium (semen) → activity .Lifespan: 6 weeks (4 weeks functionally) . NPY.End Piece .Negative Feedback in Pre-Puberty Male (GnRH) Inhibit: GABA. Melatonin Stimulate: Glutamate Puberty: [GABA].overweight children have greater chance of going into puberty at an earlier age [GnRH] → LH. [Melatonin]. [NPY] [Glutamate].Acrosome . [Leptin] Pre-Puberty: [LH] < [FSH] Puberty: [LH] > [FSH] *** fat = [Leptin] .Nucleus .Head .
albumin.ex: sex-hormone binding protein.negative feedback from esterogen produced by Sertoli cells 2) Growth of Leydig Cell (trophic effect) 3) Prolactin assists – increase LH receptors 4) IGF-1 enhances testosterone synthesis 5) FSH facilitates LH action on Leydig Cells Testosterone must be transported by Binding Proteins ..in many cells.actions can be regulated through [receptor] Effects of Testosterone and other Sex Hormones . corticosteroid-binding proteins Testosterone sets the basal production rate of sperm – but it is augmented by FSH FSH effects on Sertoli Cell (via cAMP) 1) Stimulate Steroli Cell maturation of germ cells 2) Increase glucose metabolism of Sertoli Cells 3) FSH and Testosterone → peptide hormones (inhibin B. testosterone converted to DHT .both testosterone and DHT bind intracellular receptor → bind transcription factor regions → activate/repress expression of genes . activin. growth factors) Mechanism of Action of Androgens .
peristaltic contractions .Male Sexual Functioning .Ejaculation (SNS) .NO and Prostaglandin E1 → [cGMP] → relaxation of smooth muscle → vasodilation Full Erection Phase .output of blood from penis is decreased by pressure on veins from engorged Cavernosa Rigid Phase .Cavernosa pressure > systolic pressure → no blood flow!! .SNS tone dominates Tumescence Phase .hypogonadotropic hypogonadism – abnormally low LH and FSH .process may be initiated by the brain .closure of internal sphincter of bladder Resolution Phase SNS activity constricts arteries → blood flow Male Sexual Act 1) Excitement – erection occurs 2) Plateau – variable time course 3) Orgasm – ejaculation (emission) .low plasma testosterone .peristaltic contractions driven by SNS 4) Resolution – relaxation → refractory period *Kallmann Syndrome – GnRH producing cells do not migrate from olfactory placode during embryogenesis .process may be initiated by afferent sensory impulses from the penis (pudendal nerve) Flaccid Phase .
Expansion → destruction of zona pellucida .facilitate penetration of zona pellucida Fertilization Process 1) Sperm reaches zona pellucida 2) Bind ZP3 receptor → bind sperm head to acrosomal membrane (species-specific!!) 3) Bind ZP2 receptor → release enzymes .Blastocyst secrete hCG → bind LH receptor → maintain corpus luteum .increase membrane fluidity .storage of lipids and glycogen .Acrosomal Reaction .Fertilization-Promoting Peptide (FPP) – inhibitory product of prostate gland .glandular structures .Implantation 5-7 days .only occurs inside female reproductive tract after seminal fluid has been washed away .only one sperm successfully penetrates the external granulosa cells and zona pellucida Route of Spermatazoa .motility of uterine tube aided by male-secreted prostaglandins in seminal fluid Capacitation .wash away FPP → activation of sperm 3) Loss of cholesterol → exposing acrosomal membrane → acrosomal reaction → enzyme release .only 50-100 sperm reach ampullary portion of fallopian tube .Uterus secrete fructose → food for blastocyst .Ca2+ influx → hyaluronidase .Corpus Luteum secrete progesterone and estrogen → suppose decidualization of uterine endometrium .Chorion secrete hCG → bind LH receptor → maintain corpus luteum .Fertilized ovum enters uterine cavity and expands (morula → blastcyst) .Female Sex Act 1) Excitement phase – PNS 2) Plateau phase – maintenance of lubricated state 3) Orgasm – SNS → uterus changes position → more “open” → cervical opening becomes more patent 4) Resolution → cervical opening remains widely opened for 20-30 minutes Impregnation .motility of spermatozoa aided by female-secreted oxytocin .final maturation process of spermatozoa 1) Increase motility ( [Ca2+] influx into sperm + increase temperature) 2) Dissipation of inhibitory factors .some sperm do not have enough enzyme 4) Increase intracellular Ca2+ and flagella action 5) Penetration of ovum cell membrane 6) Polyspermy block – PLC → [Ca2+] → cortical granules inactivate ZP3/ZP2 + harden zona pellucida Transport of Fertilized Ovum .
Progesterone block – suppress contractility of uterine smooth muscle .development of mammary glands → ductal and alveolar growth Human Chorionic Gonadotropin (hCG) . E3) → must transport androgen to placenta .Increased ventilation ( 50%)– increased oxygen consumption .relaxation of pelvic ligaments .The Placenta . Ions – simple diffusion Waste Products (Urea.support endometrium (decidualization) .week 10 – placenta primary source .Transports molecules to and from the fetus .progesterone stimulates medullary respiratory centers Hormones of Pregnancy Progesterone (major) . breast.Fetal PaO2 = 30 mmHg .stimulate growth of myometrium.Major endocrine gland . Creatinine) – simple diffusion .development of mammary glands → ductal and alveolar growth . uterus.Fetal kidney . Free Fatty Acids.synthesis is a coordinated effort of fetal.Androgen – DHEA (fetal) – cannot convert to progesterone or estrogens (E1.HbF – has higher affinity for oxygen than HbA . mammary ducts. and maternal tissue 1) Maternal – produce cholesterol 2) Placenta – convert cholesterol to pregnenolone 3) Fetal Adrenal Gland – convert pregnenolone to androgens (DHEA) .Estriol (E3) major product of placenta during pregnancy (Estradiol still in larger amounts) ***Progesterone and Estrogen released in multi-organ system → many points of control and regulation .Fetal lung – external respiration . external gentalia .Maternal PaO2 = 50 mmHg .Fetal gut .mother = open circulatory systems (open chambers = intervillous space) .produced by synctiotrophoblasts .fetus = closed circulatory system CO2 – simple diffusion Glucose – facilitated diffusion Lipids.switch pregnancy metabolism from anabolic to catabolic phase Estrogen . E2. Uric acid.LH-like activity → rescue/sustain corpus luteum + growth factor + prepare endometrium for implantation Human Chorionic Somatomammotropin (hCS) – growth hormone . maternal.Serve as: .handle low quantities of O2 .
Fasting Plasma Glucose > 126 mg/dL .Increase risk of developing type 2 diabetes (maternal) .allow growing fetus to utilize energy stores (catabolic) Prolactin – produced by anterior pituitary Aldosterone – increased secretion to compensate “increased plasma volume” due to amniotic/fetal fluid Cortisol – increased levels due to increased estrogen-induced increases in cortisol-binding globulin Thyroxin – increased levels due to increased estrogen-induced increases in thyroid-binding globulin Calcitriol – increased to ensure adequate calcium absorption for fetal growth Maternal PTH – decreased by 50% to prevent demineralization of maternal bone Metabolism of Pregnancy Anabolic Phase – first half ..Early Pregnancy – sensitive .Late Pregnancy – insensitive .building up energy reserves .build energy stores for fetus (anabolic) .insulin resistance – low insulin sensitivity .with assistance of maternal tissue → convert to estrogens and progesterone 4) Placenta – convert androgen (DHEA) to estrogen/progesterone Insulin .increased maternal lipolysis Most dramatic increase of blood/plasma volume and fetal weight = last 2 months Increased GFR and urine volume *Gestational Diabetes Mellitus (GDM) .high insulin sensitivity Catabolic Phase – second half (particularly late second half) .accommodate growing needs of fetus .
. polyhydromnios.Fetal Effect: excessive weight gain.Risk: acute renal failure. edema . obesity.Risk Factors: family history. overweight babies. postnatal hypoglycemia *Preeclampsia – increased blood pressure during pregnancy . hyperglycemia. hepatic failure. DIC. advanced maternal age . cerebral hemorrhage. retardation.
Week 6 1) Primordial germ cells migrated to genital ridges → induce development of gonads 2) Primitive sex cords – invaginations of epithelium into the mesenchyme 3) Paramesonephric (Mullerian) Duct – invagination of coelomic epithelium 4) Mesonephric (Wolffian) Duct ***If Primordial germ cells fail to reach genital ridge by week 5 → gonads do not develop 2) Know the derivatives of mesonephric duct and paramesonephric ducts Genital Ducts (Males) . spherical) become visible – endoderm origin .Development of Mesonephric (Wolffian) Ducts 1) Appendix Epididymis – vestigial appendage from cranial mesonephric duct 2) Ductus Epididymis 3) Ductus Deferens .Primitive Urogenital Sinus (Paramesonephric/Mullerian Tubercle) → seminal colliculus Genital Ducts (Female) .Week 4 – primordial germ cells (large.Development of Excretory Mesonephric Tubules 1) Paragenital tubules → Paradidymis – vestigial appendage from caudal excretory tubules 2) Epigenital Tubules → Ductuli efferentes .Primitive Urogenital Sinus (Paramesonephric/Mullerian Tubercle) Week 9 – two invaginations on lateral borders → Sinovaginal bulbs Month 3 – elongation of sinovaginal bulbs towards vaginal plate → elongation of vagina → hymen Month 5 – complete canalization . 1) Know embryonic origin of gonads and primordial germ cells Indifferent Gonads .Ovaries – upper border of Broad Ligament of uterus 3) Upper Part of Vagina .Broad Ligament of Uterus – separate Uterovesical pouch and Uterorecal pouch .developed from proliferation of epithelium and condensation of underlying mesenchyme .Development of Paramesonephric (Mullerian) Duct 1) Fallopian Tubes (Oviduct) 2) Fusion of Paramesonephric Ducts → Uterine Canal → Body of Uterus .Development of Mesonephric (Wolffian) Ducts 1) Epoophoron – vestigial structure from cranial mesonephric duct + excretory ducts 2) Proophoron – vestigial structure from caudal excretory tubules 3) Gartner’s Cyst – vestigial structure from caudal mesonephric duct .Development of Paramesonephric (Mullerian) Duct 1) Utriculus Prostaticus (Prostatic Utricle) – “little uterus” 2) Appendix testis .
Vagina – dual origins 1) Paramesonephric Duct 2) Primitive Urogenital Sinus (Sinovaginal Bulb) Homologues Prostate Gland (male) Prostatic Urethra → Urethral (Paraurethral) glands of Skene (female) Bulbourethral glands (male) Urogenital Sinus → Greater vestibular gland (of Bartholin) (female) Seminal Vesicle (male) Mesonephric Duct 3) Know the structure and formation of indifferent gonads 4) Know the key factor for sex dimorphism Urogenital System – derived from intermediate mesoderm .Phallus – rapid elongation of genital tubercle along with urethral folds under influence of androgen .Prepuce – foreskin External Genitalia Genital Tubercle → clitoris Definitive Urogenital Sinus → vestibule Urethral fold → labia minor . labia major (female) Week 11 – female genital tubercle longer than males at this time External Genitalia Definitive Urogenital Sinus → penile urethra Urethral Fold → Corpus cavernousum surrounding penile urethra Genital Fold → scrotum .Navicular Fossa – glandular part of urethra – derived from ectoderm .male and females are virtually identical until the end of the 6th week .Urethral Plate – line penile urethra – derived from distal urogenital sinus .Genital Tubercle – cranial union of cloacal folds Week 6 – Cloacal folds → Urethral and Anal Folds – caudal union of cloacal folds .male development instigated by SRY on Y chromosome 5) Understand the formation of the testis or ovary from the indifferent gonads Testes 1) Mullerian Inhibiting Substance (MIS) (Anti-Mullerian) → suppress paramesonephric ducts 2) Testosterone (Leydig cells) → stimulate mesonephric duct + 5-reductase → dihydrotestosterone → stimulate external genitalia development Ovaries .Genital Swellings → scrotal swelling (male).Estrogen – also produced by placenta → Stimulate paramesonephric ducts → Stimulate development of external genitalia 6) Development of genitals External Genitalia (Indifferent Stage) Week 4 – Cloacal folds – derived from mesenchyme .fusion of urethal folds → corpus spongiosum surrounding penile urethra .
Genital swelling → labia major 7) Know the embryonic origin of the Sertoli cells.Primordial Germ cells → spermatogonia .Surface Epithelium of Celom → Sertoli cells .externally female but no menstruation or secondary female characteristic *Turner Syndrome (45 X) – female – gonadal dysgenesis. reduced production of androgen and MIS *Hypospadias – incomplete fusion of urethral folds → abnormal openings of urethra along ventral (inferior) border *Epispadias – urethral opening found on dorsal (superior) aspect of penis *Micropenis – insufficient androgen stimulation .testis present .Mesenchyme of Genital Ridge → Leydig cells . Gynecomastia. and follicular cell SRY gene → Testis Determining Factor (transcription factor) → stimulate differentiation of Sertoli/Leydig cells Primitive Sex Cord . webbed neck.oocyte absent . malignancy 3% of male newborns 30% of premature Treat: corrective surgery > 1 year .ex: Congenital Adrenal Hyperplasia (CAH).Female (46 XX) .ovary present . short. Leydig cell.ex: androgen insensitivity syndrome.Male (46 XY) .Excretory Mesonephric Tubules → Ductuli Efferentes . consumption of androgenic agents during pregnancy . cardiac/renal abnormalities *True Hermaphrodites – both testicular and ovarian tissue *Pseudohermaphrodites – genotypic sex is masked by phenotypic sexual appearance .Mesonephric Duct → Ductus Deferens Primitive Sex Cord 1) Continue proliferation and elongation → medullary cords 2) Degeneration of medullary cords 3) Replacement of medullary cords by ovarian medulla Week 7 – 2nd generation of cords from surface epithelium – Cortical Cords Month 4 – Cortical Cords split into cell clusters – Follicular Cells → primordial follicular cell → oogonia 8) Know the mechanism of developmental abnormalities *Klinefelter Syndrome (47 XXY/XXXY) – males – infertility. impaired sexual development *Swyer Syndrome (XY Female Gonadal Dysgenesis) – point mutation or deletions of SRY gene .continue proliferation and elongation → medullary cord → Rete testis → Seminiferous tubule – horseshoe-shaped testis cords (canalize at puberty) .Secondary – hypothalamic or pituitary dysfunction *Bifid/Double Penis – genital tubercle splits *Hydrocele *Indirect Inguinal Hernia *Cryptorchidism – undescended testis → risk for sterility.Primary – Hypogonadism .
Uterus Bicornis Unicollis – complete or partial atresia of one of the paramesonephric ducts *Atresia of Cervix – atresia of both paramesonephric ducts *Atresia of Vagina – sinovaginal bulbs fail to develop 9) Know the mechanism of the descent of testis and ovaries Descent of Testis . *Imperforated Hymen – birth defect → hymen complete tissue plate → accumulation of fluids Hydrometrocolpos – accumulation of menstrual blood *Duplication of Uterus – lack of fusion of paramesonephric ducts .Uterus Bicornis – most common – partial fusion of paramesonephric duct .Uterus Didelphys – double vagina – sinovaginal bulbs fail to fuse .Uterus Arcuatus – least severe – indentation of upper border of uterus .descent mediated by shortening of gubernaculums → pulls testis down toward scrotum Week 12 – inguinal region Week 28 – inguinal canal Week 33 – scrotum Descent of Ovaries Gubernaculum → ovarian ligament + round ligament of the uterus .
Bulbourethral/Cowper’s) Testes Tunica vaginalis – remnant of process vaginalis – does not extend posteriorly Tunica albuginea – thick connective tissue capsule 1-4 seminiferous tubules per lobule → straight tubules → retes testis (in mediastinum testis) → efferent ductules → ductus epididymis → ductus deferens → ampulla + seminal vesicle → ejaculatory duct (distal ductus deferens) → membranous urethra + bulbo-urethral gland → penile urethra Function – Spermatogenesis .highly sensitive process . 4N) → Meiosis I .characteristic condensed chromosomes → secondary spermatocyte (1n.rest at basal aspect – larger cell . ducts. glands (seminal vesicles.pampiniform plexus surrounds testicular artery → decrease arterial blood temperature 1) Infections – Mumps → mumps orchitis → possible loss of stem cells 2) Radiation 3) Drugs – diethylstilbestrol (DES) – synthetic estrogen used during cancer treatment or pregnancy → birth defects → increased risk of genital related cancers + sterility in males 4) Hormonal Imbalance – excessive androgen use 5) Cryptochordism (Undescended testis) – temperature in undescended testis → no spermatogenesis Seminiferous Tubules Interstitium Leydig (Interstitial) Cells – production of testosterone Myoid Cells – contractile Fibroblast Cells Seminiferous Epithelium Spermatogenic Cells Sertoli (Sustentacular) Cells Spermatogenesis . 2N) → Meiosis II . prostate.approx.temperature must be 2-3 centigrade below normal body temperature .not synchronized process → constant production and supply of sperm Spermatogonia (Spermatocyte → Spermatid) → Type A – true stem – maintain population of stem cells → produce more spermatogona → Type B – progenitor cell → primary spermatocytes (2n.Primary Reproductive Organs – Testes Accessory Reproductive Structures – scrotum. 64 days .simple cuboidal appearance .early spermatid .short-lived → Spermatid (1n. normal diploid number is attained . 1N) – with fertilization.
blood-testis barrier prevents exposure to immune system → Basal Compartment – stem cells (spermatogonia) → Adluminal (Luminal) Comparment – maturation of spermatocytes and successive generations Leydig Cell .Phagocytosis of residual bodies .columnar in shape .Support.Mitochondria migrate towards middle-piece 3) Acrosome Phase . protection..differentiate by location and by morphology Sertoli Cells .Production of Anti-Mullerian Hormone .Acrosomal vesicles → acrosomal cap .Golgi complex → acrosomal vesicles 2) Cap Phase .secretion of testosterone .irregular shaped.inhibin + activin modulate FSH release .associated with chronic respiratory infections Know how to recognize cells in each phase of spermatogenesis .Production of Androgen Binding Protein (ABP) – transport testosterone to seminiferous tubule . filled with lipid droplets → foamy appearance The Duct System Intratesticular Genital Ducts Straight Tubules – lined with sertoli cells (abruptly join retes testis → abruptly becomes simple cuboidal) Retes testis – lined with simple cuboidal cells Proximal ductuli efferentes – lined with tall columnar ciliated cells and shorter non-ciliated cells → scalloped appearance .Manchette (microtubules) – condensation and elongation of the nucleus 4) Maturation Phase .under control of FSH .Secretion of fluid for sperm transport . acidophilic.Residual body *Immotile Cilia Syndrome – immotile spermatozoa due to lack of dynein or other proteins → infertility .Function: .Blood-Testis Barrier = Sertoli-Sertoli junctional complex – bound together by occluding junctions .late spermatid – attached to luminal aspect of sertoli cells Spermiogenesis (Spermatid → Spermatozoa) .newly formed spermatozoa are immotile – will mature will traveling through the ductile system 1) Golgi Phase .under control of LH .Centrioles → developing acrosomal complex . nutritional regulation .
non-ciliated cells absorb testicular fluid .Principal Cell – with stereocilia. columnar .Middle circular .non-ciliated cells absorb testicular fluid ..thin circular layer of smooth muscle outside basal lamina → peristalsis Excretory Genital Ducts Distal ductuli efferentes – lined with tall columnar ciliated cells and shorter non-ciliated cells → scalloped appearance . squamous.Outer longitudinal Ejaculatory duct – lined with simple or pseudostratified columnar epithelium without muscular layers .two highly tortuous tubes (15 cm) → honeycomb appearance (highly secretory epithelium) .Basal Cell – stem cell .due to thicker walls and easily “seen” through scrotal skin + easy to access and identify Accessory Genital Glands Seminal Vesicle .circular muscular layer → peristalsis Ductus deferens – lined with pseudostratified columnar with stereocilia .three layers: 1) Mucosa 2) Muscularis (inner circular.formed by junction of ductus deferens (ampulla) and seminal vesicle Urethra *Vasectomy – cut through ductus deferens .lined with simple columnar though cuboidal.Inner longitudinal .) .contain sperm-activating substances (fructose.ciliated cells helps transport sperm .aggregation of many glands . prostaglandins.largest accessory organ .main storage site of sperm .sperm mature → motile at distal part of ductus epididymis .ciliated cells helps transport sperm .secretions = 70% of ejaculation .thin circular layer of smooth muscle outside basal lamina → peristalsis Ductus epididymis – lined with pseudostratified columnar with stereocilia . etc.Muscular Layers – very muscular → narrow lumen . outer longitudinal) 3) Adventitia rich in elastic fiber Prostate Gland .Prostatic Concretions (corpora amylacea) – calcified glycoproteins in lumen of glands .segment leaving prostate .outgrowth of ductus deferens – lined with pseudostratified or simple columnar epithelium . citrate. tall. or pseudostratified epithelium may be visible .
Flaccid: shunt between deep artery and deep dorsal vein remains open .major site for prostate cancer Transitional Zone (5%) .consist of three parallel cavernous bodies .site where BPH usually originates Central Zone (25%) .submucosal glands .Peripheral Zone (70%) .prostatic-specific antigen (PSA) – elevated during malignancy Bulbourethral (Cowper’s) Glands .two pea-sized structures .outer (main) glands .clear viscous secretions → lubricating function prior to ejaculation Penis .lined by simple cuboidal epithelium .Rection: shunt is closed due to expansion of erectile tissue → closure of deep dorsal vein Erection – PNS Ejaculation – SNS *Sildenafil (Viagra) – block phosphodiesterase (PDE) → prevent breakdown of cGMP → continual vasodilation → erection .mucosal gland *Benign Prostatic Hyperplasia – 40-50% of men → obstruction of urethra *Malignant Prostatic Tumor – second most common cancer in men and third leading cause of cancer deaths .
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue reading from where you left off, or restart the preview.