Prefertilization Events

Development of gonads: The gonad region forms as a longitudinal elevation of intermediate mesoderm called the urogenital ridge & differentiates into either the testes or ovary only after being populated by primordial germ cells which migrate to it from the wall of the yolk sac at week 4 of human development..

Testes development is directed by: a) Sry gene on the short arm of Y chromosome encodes for the testes-determining factor !T"#. b) Testosterone which is secreted by the $eydig cells. c) %ullerian-inhibiting factor %&"# which is secreted by Sertoli cells. 'o factors are needed for development of the ovary.

Gametes (oocytes & sperms): !escendants of primordial germ cells which originate in the wall of yolk sac of the embryo & migrate to the gonad region at week 4. They are produced in adults by gametoenesis oogenesis in females & spermatogenesis in males# that involve meiosis. Chromosomes: State of chromosomes:

Ploidy: number of chromosomes in a cell either () haploid# or 4* diploid#. N number: amount of !'+ in a cell ,'- (' or 4'. - ' number depends on the ploidy & state of chromosomes Haploid cells (23 chromosomes) iploid cells (!" chromosomes) Single ouble Single ouble N number ,' (' (' 4' Normal somatic cells contain 4* single chromosomes 4*- ('# arranged in () homologous pairs homologues#- one chromosome of each pair is of maternal origin & the other is of paternal origin. - .airs ,-(( autosomal non-se/# chromosomes. - .air () se/ chromosomes 00 for females or 0Y for males#. #ametes contain () single chromosomes ()- ,'# - Female gametes contain only the 0 se/ chromosome. - Male gametes contain either the 0 or Y se/ chromosome- so it is the male gamete that determines the genetic se/ of the offspring.

$ell type
'ormal somatic cells .rimordial germ cells- oogonia- spermatogonia- 1ygote- blastomeres ,ry oocyte- ,ry spermatocyte (ry oocyte- (ry spermatocyte 2ocyte ovum#- spermatid- sperm

Ploidy% N number 4*- ('

4*- 4' ()- (' ()- ,'

Meiosis: Speciali1ed process of cell division that occurs only during the production of gametes. 3onsists of ( cell divisions meiosis & & meiosis &&# that results in 4 gametes each is ()- ,'.

&enefits of meiosis: 1. 4educes the number of chromosomes within the gametes to maintain the human species number of chromosomes 4*# between generations. 2. 4edistributes maternal & paternal chromosomes to ensure genetic variability. 3. .romotes e/change of small amounts of maternal & paternal !'+ via crossover during meiosis &

'mportant events during meiosis:

Synapsis $rossing over )lignment * dis+unction $ell division

(eiosis ' .airing of 4* homologous double chromosomes 5/change of segments of paternal & maternal !'+ 4* homologous double chromosomes align at the metaphase plate & separate from each othercentromeres don6t split Two (ry gametocytes- each is ()- ('

(eiosis ''
+bsent +bsent () double chromosomes align at the metaphase plate- centromeres split 4 gametes- each is ()- ,'

 Nondisjunction: if dis7unction doesn6t occur during meiosis & or &&- e8uivalent chromosome separation doesn6t occur resulting in abnormal gametes with (4 single chromosomes & (( single chromosomes. Trisomy results from fertili1ation between normal gamete () single chromosomes# & abnormal gamete (4 single chromosomes# 1ygote with 49 single chromosomes. (onosomy results from fertili1ation between normal gamete () single chromosomes# & abnormal gamete (( single chromosomes# 1ygote with 4: single chromosomes.

Female gametogenesis (oogenesis): Primordial germ cells 4*- ('# reach the ovary at week 4 of embryonic development & differentiate into oogonia 4*- ('# enter meiosis & & undergo !'+ replication to form ,ry oocytes 4*- 4'#. +ll ,ry oocytes are formed by the :th month of fetal life & remain dormant in the prophase diplotene# of meiosis & until puperty ,st arrested stage of meiosis#. 'o oogonia are present at birth. +fter puberty & during a woman6s ovarian cycle- a ,ry oocyte completes meiosis & to form a 2ry oocyte ()('# & the ,st polar body which degenerates.

The (ry oocyte enters meiosis && & ovulation occurs when the chromosomes align at the metaphase. The (ry oocyte remains arrested in the metaphase of meiosis && until fertili1ation occurs (nd arrested stage of meiosis#. +t fertili1ation- the (ry oocyte completes meiosis && to form the mature oocyte ()- ,'# & (nd polar body. N-&-% with each ovarian cycle- about :-,: ,ry oocytes will begin maturation & only one reaches full maturity. N-&-% oocytes that ovulated late in a woman6s reproductive life may have been dormant for as long as 4; years.

)ppro.imate number of oocytes: a) ,ry oocytes: - +t month : of fetal life 9 millions. - +t birth ( millions : millions have degenerated#. - +t puberty 4;-;;; ,.<* millions more have degenerated#. b) 2ry oocytes: - ,( are ovulated per year up to 4=; over the whole reproductive life of the woman 4; years# this number is >ed by pregnancy ovulation stops#- birth control pills prevent ovulation# & in women who have anovulatory cycles. .rolonged dormancy of ,ry oocytes may be the reason for the high incidence of chromosomal abnormalities in the offspring of old women such as !own syndrome trisomy (,#.

Male gametogenesis (spermatogenesis): ) phases A. Spermatocytogenesis: Primordial germ cells 4*- ('# reach the testes at week 4 of embryonic development & remain dormant until puberty at which they differentiate into type ) spermatogonia 4*- ('# undergo mitosis to provide a continuous supply of stem cells throughout the male reproductive life. Some type + spermatogonia differentiate into type & spermatogonia 4*- ('#. B. (eiosis: type ? spermatogonia enter meiosis & & undergo !'+ replication to form two ,ry spermatocytes 4*- 4'# which complete meiosis & to form 2ry spermatocytes ()- ('# enter & complete meiosis && to form 4 spermatids ()- ,'#. C. Spermiogenesis: Spermatids undergo a postmeiotic series of morphologic changes to form sperms ()- ,'# which include formation of the acrosome- condensation of the nucleus & formation of the head- neck & tail. The total time of sperm formation from spermatogonia to sperms# is about *4 days. 'ewly e7aculated sperms are incapable of fertili1ation until they undergo capacitation which occurs in the female reproductive tract. $apacitation takes about 9 hours & involves unmasking of glycosyltransferases on the sperm cell membrane & removal of proteins that coat the surface of the sperm derived from the seminal fluid#. N-&-% there is an increased incidence of achondroplasia in the offspring of old (ale fertility depends on the number & motility of the sperms. "ertile males produce (;-,;; million sperm@ml of semen- normally up to ,;A of which may be grossly deformed ( heads or ( tails#. ormonal contraception: 1. /ral contraceptives: a) $ombination pills - 3ontain both estrogen & progesterone. - Taken for (, days & discontinued for 9 days. - Mechanism of actionB prevent ovulation by -

b) Progesterone0only pills 3ontain progesterone only Taken continuously Cnknown mechanism of action-

however

inhibiting secretion of Dn4E- "SE & $E

progesterone causes thickening of cervical mucus making it hostile to sperm migration & thinning of the endometrium making it unprepared for conceptus implantation.

2. (edro.yprogesterone acetate (1 epo0Provera): progesterone-only in7ection form- given &% & will prevent ovulation for (-) months. 3. 2evonorgestrel (Norplant): progesterone-only product within capsules implanted subdermally that will prevent ovulation for ,-: years. 4. Postcoital contraception (morning0after pill): !iethylstilbestrol (: mg taken twice a day for : days or ( combination pills up to 9( hours postcoital followed by ( pills ,( hours later. &f failed- therapeutic abortin is recommended because of the potential teratogenic effects of steroids.

Week 1 of human development (days 1-7)

Fertili!ation: 2ccurs in the ampulla of the uterine tube. The sperm penetrates corona radiate & then binds to the 1ona pellucida of the (ry oocyte & triggers the acrosome reaction causing the release of acrosomal en1ymes acrosin# which helps the sperm penetrating the 1ona pellucida. .enetration of 1ona pellucida triggers the cortical reaction rendering the (ry oocyte impermeable to other sperms. The sperm & (ry oocyte cell membranes fuse & the contents of the sperm enter the cytoplasm of the oocyte. - The male genetic material forms the male pronucleus. - The tail & mitochondria of the sperm degenerate- so all mitochondria within the 1ygote with their mitochondrial !'+ are of maternal origin. The (ry oocyte completes meiosis &&- thus forming a mature ovum- the nucleus of which forms the female pronucleus.. The male & female pronuclei fuse to form a 1ygote.

Cleavage: + series of mitotic divisions of the 1ygote with no change in the si1e of the cytoplasm blastula which consists of increasing smaller cells called blastomeres. +t the )(-cell stage- the blastomeres form a morula which consist of an inner cell mass & outer cell mass. '.?.- blastomeres are totipotent cells up to the =-cell stage each cell can form a complete embryo by itself#. "lastocyst formation: "luid is secreted within the morula forming the blastocyst cavity. The inner cell mass is now known as the embryoblast will become the embryo. The outer cell mass is now known as the trophoblast will become the fetal portion of the placenta. #mplantation: Fona pellucida must degenerate for implantation to occur. The blastocyst implants within the functional layer of the endometrium in the posterior superior wall of the uterus during the secretory phase of the menstrual cycle. The embryonic pole of the blastocyst implants first. The trophoblast differentiates into cytotrophoblast & syncytiotrophoblast.

 $c to pi c

tu%al pregnancy: The most common course of ectopic pregnancy. 2ccurs when the blastocyst implants within the uterine tube most commonly in the ampulla due to delayed transport. 3is4 factors: endometriosis- pelvic inflammatory disease due to adhesions#. $linical picture: abnormal uterine bleeding- sudden onset of unilateral pelvic pain- last period *; days agoGve h3D test & culdocentesis showing intraperitoneal blood. ifferential diagnosis: appendicitis- aborting intrauterine pregnancy & bleeding corpus luteum of a normal intrauterine pregnancy. 5ctopic abdominal pregnancy: occurs most commonly in the rectouterine pouch !ouglas pouch#. &'inning: 1. i6ygotic (fraternal) t7ins: result from fertili1ation of ( different (ry oocytes by ( different sperms ( 1ygotes ( blastocysts each implants separately ( placentae- ( chorions & ( amniotic sacs genetically different twins. 2. (ono6ygotic (identical) t7ins: result from fertili1ation of one (ry oocyte by , sperm , 1ygote , blastocyst whose inner cell mass embryoblast splits into two genetically identical twins. &n *:A of cases- the fetuses has , placenta- , chorion & ( amniotic sacs. &n ):A of cases- the fetuses has ( placentae separate or fused#- ( chorions & ( amniotic sacs. &f the embryoblast doesn6t split completely- the ( embryos will be 7oined by a tissue bridge- e.g.- at the head- thora/ or pelvis con+oined (Siamese) t7ins.

#n vitro fertili!ation (#(F):

Week 2 (days 8-14)

$m%ryo%last development: the embryoblast differentiates into ( distinct cell layers the epiblast dorsally & hypoblast ventrally forming a bilaminar embryonic dis4. 3lefts develop within the epiblast & coalesce to form the amniotic cavity dorsally. The entire future development of the embryo arises from the epiblast

3ells from the hypoblast migrate along the cytotrophoblast to line its inner surface forming the e/ocoelomic membrane which limits the blastocyst cavity ventrally- now known as the e.ocoelomic cavity & later will be the yol4 sac after a portion of the e/ocoelomic cavity separates forming e/ocoelomic cyst. +t the future site of the mouth- hypoblast cells fuse with epiblast cells forming the prochordal plate.

&ropho%last development: A. Syncytiotrophoblast: The outer multinucleated 1one of trophoblast. +rises from the cytotrophoblast as it doesn6t divide mitotically. &t continues its growth into the endometrium & erodes endometrial blood vessels & glands forming lacunae filled with nutritive maternal blood & glandular secretions. &solated lacunae fuse to form a lacunar net7or4. %aternal blood flows in & out of the lacunar network- thus forming early uteroplacental circulationdespite of which- the embryoblast receives maternal nutrients via diffusion. The endometrial stromal cells at the site of implantation become filled with glycogen & lipids decidual cells. ecidua is the name applied to the endometrium during pregnancy which is shed after childbirth. The syncytiotrophoblast secretes h$# which is a glycoprotein that stimulates secretion of progesterone by the corpus luteum to maintain pregnancy until week = then the placenta takes over progesterone secretion. h3D is the basis of early pregnancy testing. &t can be assayed in maternal blood at day = or in maternal urine at day ,; & is detectable throughout pregnancy.. High h$# levels may predict multiple pregnancy- hydatidiform mole or choriocarcinoma. 2o7 h$# levels may predict spontaneous abortion or ectopic pregnancy. B. $ytotrophoblast: %itotically active adds to the growth of syncytiotrophoblast. 'ew cytotrophoblastic cells produce local mounds called ,ry chorionic villi which protrude into the surrounding syncytiotrophoblast. $)traem%ryonic mesoderm: + new layer of cells derived from the epiblast that separates the e/ocoelomic membrane & cytotrophoblast. Spaces develop within the e/traembryonic mesoderm & coalesce to form the e.traembryonic coelom which is called later the chorionic cavity.

The e.traembryonic coelom divides the e.traembryonic mesoderm into: A. 5.traembryonic somatic mesoderm (somatopleuric mesoderm): lines the cytotrophoblast- forms the connecting stal4 from which the conceptus suspends within the chorionic cavity & covers the amnion. B. 5.traembryonic visceral mesoderm (splanchnopleuric mesoderm): covers the yolk sac.
The wall of the chorionic cavity is called the $horion & consists of ) layers e/traembryonic somatic mesoderm- cytotrophoblast & syncytiotrophoblast.

 *ncofetal antigens: 3ell surface antigens that normally appears only on embryonic cells. "or unknown reasons- they re-e/press themselves in human malignant cells- e.g.- carcinoembryonic antigen 35+# in colorectal cancer & 80fetoprotein in hepatoma & germ cell tumors. Mifepristone (+,-./0): &t blocks progesterone receptors & will initiate menstruation when taken within =-,; weeks of the last period. &f implantation has occurred- the conceptus will be sloughed along with the endometrium. <*A effective in terminating pregnancy when used in con7unction with prostaglandins .D5( & .D"(H# which induce uterine contraction.

Em ryoni! period ("eeks #-8)

 Ieek ) of embryonic development coincides with the ,st missed menstrual period which is the ,st indication of pregnancy. 5mbryonic period is a period of high susceptibility to teratogens. +ll ma7or organ systems begin to develop during the embryonic period causing a craniocaudal & lateral body folding of the embryo. ?y the end of the embryonic period- the embryo has a distinct human appearance. Gastrulation: &t is the process that establishes the ) definitive germ layers of the embryo ectoderm- mesoderm & endoderm- thus forming a trilaminar embryonic dis4 by day (, of development. These ) layers give rise to all tissues & organs of the adult. &t is first indicated by the formation of the primitive strea4 within the epiblast which consists of the primitive groove- primitive node & primitive pit. +ll the ) layers are formed by migration of epiblast cells through the primitive streak. - 5piblast cells migrate to the primitive streak & insert themselves between the epiblast & hypoblastsome displace the hypoblast to form the endoderm- others migrate cranially- caudally & laterally to form the mesoderm & now the epiblast is called the ectoderm. 3ranial to the primitive streak is the prochordal plate which is the future site of the mouth & 3audal to it is the future site of the anus- known as the cloacal membrane.

5ctoderm is involved in the formation of the nervous system neuroectoderm & neural crest# & epidermis of the skin. (esoderm gives further rise to:

a) Para.ial mesoderm: - 2n each side of the midline. - ?ecomes organi1ed into segments called somitomeres which form in a craniocaudal se8uence. - Somitomeres ,-9 contribute mesoderm to the pharyngeal arches. - The remaining somitomeres form ): pairs of somites which further differentiate intoB 1. Sclerotome gives rise to bone & cartilage. 2. Myotome gives rise to muscle. 3. Dermatome gives rise to dermis of the skin. b) 'ntermediate mesoderm: forms a longitudinal dorsal dorsal ridge called the urogenital ridge formation of the kidneys & gonads. c) 2ateral mesoderm: gets divided by the intraembryonic coelom into intraembryonic somatic mesoderm & intraembryonic visceral mesoderm. &ntraembryonic coelom forms the body cavities pleural cavitypericardial cavity & peritoneal cavity#.

Notochord: solid cylinder of mesoderm e/tending in the midline of the trilaminar embryonid disk from the primitive node to the prochordal plate. 't serves the follo7ing: - &t induces the overlying ectoderm to differentiate into the neuroectoderm neural plate neural tube. - &t induces formation of the vertebral bodies. - &t forms the nucleus pulposus of intervertebral disks.

$ardiogenic area: horseshoe-shaped region of mesoderm located at the cranial end of the trilaminar embryonic disk & is involved in the formation of the future heart. 1acrococcygeal teratoma: Tumor that arises from remnants of the primitive streak which normally degenerates & disappears.

&t is derived from pluripotent cells of the primitive streak- that6s why it contains various types of tissues e.g.bone- nerve- hair#. &t occurs more commonly in female infants. &t usually becomes malignant during infancy & must be removed by * months of age.

Chordoma: ?enign or malignant tumor that arises from remnants of the notochord. %ay be found intracranially or in the sacral region. &t occurs more commonly in men late in life above :; years#. Caudal dysplasia (sirenomelia): + groups of syndromes ranging from minor lesions of the lower vertebrae to complete fusion of the lower limbs. 4esults from abnormal gastrulation in which migration of the mesoderm is disturbed. &t can be associated with either 9)T53 or 9)$T5329 9ertebral defects 9 ) )nal atresia ) $ $ardiovascular defects T TracheoT 5sophageal fistula 5 5 3 3enal defects 3 2 Cpper 2imb defects

Pla!enta$ amnioti! fluid % um ili!al !ord

 Decidua is the name applied to the endometrium during pregnancy. &t consists ofB 1. ecidua basalis: part of the decidua on which the implanted blastocyst rests. 2. ecidua parietalis: part of the decidua other than the site of implantation. 3. ecidua capsularis: part of the decidua that covers the blastocyst & separates it from the uterine cavity. +s the fetus grows- it e/pands & fuses with the decidua parietalisthus obliterating the uterine cavity. Chorion: $horionic villi develop in relation to the decidua basalis- they proceed from ,ry to (ry to )ry chonionic villi which form the villous chorion. The part of chorion covered by the decidua capsularis has no villi smooth chorion. +s the fetus grows- the amnion e/pands toward & fuses with the smooth chorion- thus obliterating the chorionic cavity & forming the amniochorionic membrane bag of waters#.

 Components of the placenta: 1. (aternal component: decidua basalis. 2. :etal component: villous chorion which consists of tertiary chorionic villi derived from the trophoblast & e/traembryonic mesoderm#. 2lacental mem%rane: Separates maternal from fetal blood & allows or denies various substances from passing through it to & out of the fetus. 'n early pregnancy% it consists of syncytiotrophoblast- cytotrophoblast $angerhans cells#- connective tissue & endothelium of the fetal capillaries. Eofbauer cells are found in the 3T & are most likely macrophages. 'n late pregnancy% the cytotrophoblast degenerates & the connective tissue is displaced by the growth of fetal capillaries- leaving only the syncytiotrophoblast & fetal capillary endothelium. 3fter%irth appearance of the placenta: A. (aternal surface: ,:-(; cotyledons mass of villi# cobblestone appearance. &t is dark red & oo1es blood due to torn maternal blood vessels. B. :etal surface: characteri1ed by chorionic blood vessels & is covered by the amnion smooth & shiny appearance.

&eneficial substances that cross the placental membrane - 2(- 32(

- Dlucose- amino acids- free fatty acids- vitamins - Iater- sodium- potassium- chloride- calcium- phosphate - Crea- uric acid- bilirubin - "etal & maternal 4?3s - %aternal serum proteins - Cncon7ugated steroid hormones - &gD which confers passive immunity to the fetus Harmful substances that cross the placental membrane - 32 - 2rganic mercury- lead - 3ocaine- heroin - Jiruses rubella- measles- 3%J- herpes simple/ type (- varicella 1oster- variola- 3o/sackiepoliomyelitis - 4ubella virus vaccine - To/oplasma gondii- Treponema pallidum - +nti-4h antibodies - 3ategory 0 drugs absolute contraindication in pregnancy# thalidomide- tria1olamcyclophosphamide- chlorambucil- methotre/ate- phenytoin- warfarin- isotretinoin- clomiphene- !5Salcohol- nicotine- oral contraceptives - 3ategory ! drugs definite evidence of risk to the fetus# tetracycline- do/ycycline- streptomycintobramycin- amikacin- .henobarbital- valproic acid- dia1epam- alpra1olam- chlordia1epo/idechlorothia1ide- lithium Substances that don;t cross the placental membrane - %aternally-derived cholesterol- triglycerides & phospholipids - .rotein hormones as insulin - &g+- &g!- &g5- &g% - ?acteria - !rugs succinylcholine- curare- heparin- methyldopa

,m%ilical cord: contains a) 3ight * left umbilical arteries carry deo/ygenated blood from the fetus to the placenta. b) 2eft umbilical vein carries o/ygenated blood from the placenta to the fetus c) (ucus connective tissue Iharton6s 7elly#. The presence of only one umbilical artery within the umbilical cord is an abnormal finding that suggests cardiovascular abnormalities. 3%normal placental shapes: 1. 9elamentous placenta: the umbilical vessels travel abnormally through the amniochorionic membrane before reaching the placenta. &f umbilical vessels cross the internal os- a serious condition called vasa previa e/ists in which- if one of the umbilical vessels ruptures during pregnancy or labor- the fetus will bleed to death. 2. &ipartite or tripartite placenta: the placenta is formed of ( or ) connected lobes. 3. uple. or triple. placenta: the placenta is formed of ( or ) separate lobes. 4. Succenturiate placenta: the placenta consists of small accessory lobes completely separate from the main placenta. 5. (embranous placenta: thin placenta that forms over the greater part of the uterine cavity.

 2lacenta previa: 2ccurs when the placenta attaches in the lower part of the uteruscovering the internal os. Cterine blood vessels rupture late in pregnancy as the uterus starts to gradually dilate. 3linically presented by repeated episodes of bright red vaginal bleeding. The mother may bleed to death & the fetus will be also at risk because of the compromised blood supply ?ecause the placenta blocks the cervical opening- deliver is usually accomplished by 3S. 2lacenta as an allograft: the fetal component of the placenta inherits both maternal & paternal genes & therefore may be considered as an allograft foreign body# with respect to the mother. Ho7ever the placenta is not re+ected in most cases o7ing to 2 factors: a) Syncytiotrophoblast cells lining the villous chorion lack %E3 antigens & thus don6t evoke an immune response. b) !ecidual cells within the endometrial stroma secrete .D5( which inhibits T-lymphocyte activation. 2reeclampsia & eclampsia: .reeclampsia refers to the sudden development of ET'- edema & proteinuria usually after week )( of pregnancy. 5clampsia includes the additional symptom of convulsions. 3is4 factors: nulliparity- !%- ET'- renal disease- twin gestation- hydatidiform mole. Treatment: termination of pregnancy as soon as possible. 2hysical inspection of the um%ilicus in a ne'%orn infant may reveal: $ight gray shining sac indicating an omphalocele. "ecal meconium# discharge indicating a vitelline fistula. Crine discharge indicating a urachal fistula. 3mniotic fluid ?asically is water that contains carbohydrates- lipids- proteins e.g.- hormones- en1ymes- H-fetoprotein#des8uamated fetal cells & fetal urine. &t is produced constantly by dialysis of maternal & fetal blood through blood vessels in the placenta & by e/cretion of fetal urine in the amniotic sac. &t is then swallowed by the fetus- absorbed into the fetal blood through the D&T- removed by the placenta & passed into the maternal blood. )mount: gradually increased during pregnancy- reaches ,;;; ml at term. *ligohydramnios: $ow amount of amniotic fluid K 4;; ml in late pregnancy. $auses: inability of the fetus to e/crete urine into the amniotic sac due to renal agenesis. &t results in fetal deformities Potter;s syndrome# & hypoplastic lungs due to increased pressure on the fetal thora/. 2olyhydramnios: 5/cess amount of amniotic fluid L (;;; ml in late pregnancy. $auses: inability of the fetus to swallow due to anencephaly or esophageal atresia. &t is commonly associated with maternal diabetes. 4-fetoprotein (3F2): fetal albumin that is produced by fetal hepatocytes. "ound in the amniotic fluid & maternal serum.

5levated +". levels are associated with neural tube defects spina bifida- anencephaly#- omphalocele allows fetal serum to leak into the amniotic fluid#- esophageal & duodenal atresia interferes with fetal swallowing#. 4educed +". levels are associated with !own syndrome.

2remature rupture of amniochorionic mem%rane is the most common cause of premature labor & oligohydramnios. 3mniotic %and syndrome: bands of the amniotic membrane encircle & constricts parts of the fetus causing limb amputations & craniofacial anomalies. Fetal angiogenesis: %esoderm differentiates into angioblasts which form angiogenic cell clusters. +ngioblasts at the periphery give rise to the endothelium of blood vessels while angioblasts within the center give rise to primitive blood cells. +ngiogenesis occurs ,st in e/traembryonic visceral mesoderm around the yolk sac on day ,9. ?y day (,- angiogenesis has occurred in the e/traembryonic somatic mesoderm around the connecting stalk to form the umbilical vessels & in (ry chorionic villi to form )ry chorionic villi. $ater on- angiogenesis occurs in the fetal mesoderm. 5ventually blood vessels formed in the e/traembryonic mesoderm will become continuous with blood vessels within the embryo- thus establishing a blood vascular system between the embryo & the mother. Fetal hematopoiesis: 2ccurs ,st within the e/traembryonic visceral mesoderm around yol4 sac during week ) embryonic hemoglobin M(N(. ?eginning at week :- hematopoiesis is taken over by a se8uence of embryonic organs liver- spleenthymus & bone marrow. - 2iver hematopoiesis fetal hemoglobin H(O( the predominant form during pregnancy. - &one marro7 hematopoiesis appro/imately week );# adult hemoglobin H(P( gradually replaces fetal hemoglobin. Fetal circulation:

3emnants created by closure of fetal circulatory structures :etal structure )dult remnant %edial umbilical ligament - 4ight & left umbilical arteries $igamentum teres - $eft umbilical vein $igamentum venosum - !uctus venosus "ossa ovale - "oramen ovale $igamentum arteriosum - !uctus arteriosus