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Oogenesis

A.

I. Differentiation of the ovum


Female Gamete formation: meiosis produces a gamete that contains all the factors needed to initiate and maintain metabolism and development (as compared to simple sperm) Haploid nucleus Cytoplasmic enzymes mRNAs organelles metabolic substrates gametes develop from primordial germ cells that migrate to the somatic gonadal precursors (genital ridges in mammals) same for drosophila, xenopus & zebrafish once the gonad is assembled, germ cells begin active proliferation and become gonial cells.

I. II.

Differentiation of the ovum Follicle formation

B. Mammals Primary oocytes progress through MI until diplotene stage arrested until puberty

Production of haploid gametes is essential for sexual reproduction

Unequal division of cytoplasm at telophase generates polar body & secondary oocyte

The large cell in the picture above is either the product of the first or second meiotic division that lives.

II. Follicle formation mechanisms of oogenesis


In all species except C. elegans, gonadal somatic cells envelop female germ cells to create a follicle Primordial Germ cells destined to become oocytes have already entered meiosis at the time of follicle formation and within the follicle they reach the diplotene stage of PI here they halt meiosis for a few days to many years, depending on the species Mechanisms of oogenesis differ among taxa because reproduction patterns also vary

A.

B.

Synchronous development leads to "cohorts" of eggs which are in the same stage of development, which reach maturity at the same time, and which are spent all at once. Hence, synchroneous gonad development is a cyclical affair: The gonad grows in size and mass during the ripening of the eggs until a distinct spawning event occurs which sets the gonad back to the initial conditions of the cycle In the gonads of species with asynchronous development we will not find "cohorts" of eggs being in the same stage of development, but there are eggs of any develop-mental stage at any time. These species show no distinct spawning times, but more or less continuous spawning all year round.

1). In Drosophila, asymmetric cell division gives rise to the oocyte


Cystoblast undergoes 4 mitotic divisions to give rise to a cyst of 16 germline cells only 1 cell develops as an oocyte within the cyst the other 15 differentiate into nurse cells

2). Oogenesis in Vertebrates


Cyst phase is confined to early ovarian development and cells in an individual cyst do not differentiate as nurse cells each germ cell has the potential to become an oocyte.

http://berglab.gs.washington.edu/movies/cy2xGFPmoe.qt

C. Egg asymmetry
it is during oogenesis that the animal-vegetal axis of the egg is specified. as a result of differential intracellular transport, the amount of yolk steadily increases in the vegetal hemisphere

Oogenesis in Xenopus Iaevis

Oogonia are found as nests of 16 pearl shaped cells that develop synchronously Oogonia are self-renewing stem cells that persist for the life of the frog Can generate a new cohort of oocytes each year

Growth of oocytes in the frog. During the first 3 years of life, three cohorts of oocytes are produced. The drawings follow the growth of the first-generation oocytes.

Ovulation in the rabbit.

The ovarian follicle of mammals. (A) Maturation of the ovarian follicle. When mature, it is often called a Graafian follicle. (B) Scanning electron micrograph of a mature follicle in the rat. The oocyte (center) is surrounded by the smaller granulosa cells that will make up the cumulus.

In humans - ovulation occurs about two weeks after the onset of menstruation. In response to a sudden surge of LH, the follicle ruptures and discharges a secondary oocyte.

Follicular growth stage & antrum formation


Ooctye undergoes 500x increase in volume increase in # of follicular granulosa cells Cavity forms (antrum) which fills with proteins, hormones & additional molecules Follicle cells secrete growth & differentiation factors Survival dependent upon gonadotropic hormones

Menstruation
I. II.
A. B. C. D. E.

I. Estrus v. Menstruation
Estrus = frenzy Estrus cycles reabsorb the endometrium if conception does not occur during that cycle. Menstrual cycles shed the endometrium through menstruation instead. Species with estrus cycles, females are generally only sexually active during the estrus phase of their cycle Females of species with menstrual cycles can be sexually active at any time in their cycle, even when they are not about to ovulate.

Estrus v. Menstruation Menstruation


Evolution of menstruation Menstrual cycle overview Physiology of menstruation Menstrual symptoms Menstruation and the environment

A. Phases of Estrus
Proestrus one or several follicles of the ovary are starting to grow, their number being specific for the species (~2-4d), endometrium starts to develop. Estrus ovarian follicles are maturing and estrogen secretions exert their maximal influence. The animal exhibits a sexually receptive behavior (i.e. lordosis reflex), a situation that may be signaled by visible physiologic changes. Ovulation may occur. Metestrus Estrogen declines, and the corpus luteum starts to form. The uterine lining is under the influence of progesterone and becomes secretory. (~1-5d) Diestrus In the absence of pregnancy the diestrus phase terminates with the regression of the corpus luteum. The lining in the uterus is not shed, but will be reorganised for the next cycle.
Anestrus phase when the sexual cycle rests (controlled by environmental cues) In cats:

B. Hormonal control & variation in cycles:


Estrogen levels rise prior to and during proestrus and fall in conjunction with the preovulatory surge of LH. Ovulation occurs after the LH surge.
Time line specific for canines

Species Hamster Sheep Horse Dog Lion

Estrus Cycle 1 2 5 7 9 4 17 21 60 55

The female on the left is in estrus: note the swelling around the top of the vagina and the presence of a small opening as well as the bright red color. The female on the right is not in estrus: note the elongated shape of the vagina, the absence of an opening and the lack of swelling around the top of the vagina.

AVERAGE LENGTHS (days) OF ESTRUS AND ESTROUS CYCLES

II. Menstruation
Myths http://news.bbc.co.uk/2/hi/south_asia/4250506.stm http://www.mum.org/ Menstruation and the moon? Lunar cycle: 29.5 days (average length of cycle) Entrainment with environmental cycles

A. Evolution of menstruation
Supporting the developing offspring inside the mothers body Place for development
uterus

B. Menstrual cycle overview


Series of cyclic changes that the uterine endometrium undergoes each month in response to changing levels of hormones in the blood Changes coordinated with the phases of the ovarian cycle Cycle - 28 days. But range from 20-40 days On average, menses lasts ~5 days Anovulatory cycles w/no ovulation Occurs between puberty and the end of the reproductive years

Nutritive connection
endometrium

Inflammatory response? Buildup of tissue in uterus parallels the inflammatory reaction Only humans & great apes exhibit menstrual cycles, in contrast to the estrus cycle of most mammalian species. Protection from disease-causing organisms introduced in semen? Woman unable to reabsorb large amount of tissue needed? Side effect of hidden ovulation?

C. Physiology of menstruation
Remarkable events: Dependant upon interrelationships between the brain, pituitary gland, ovaries & uterus
All controlled by hormones

Preparation of egg for fertilization, preparation of uterus for pregnancy, evaluation of pregnancy status, reabsorption and excretion, begin again Phases: Menstrual, Proliferative, Secretory

Estrogen, acting via the ER, regulate growth and differentiation of cells.

Coiled spiral arteries

Endometrium has 2 layers, 1) superficial layer and 2) basal layer Superficial layer responds to hormones & undergoes major changes Basal layer remains the same Regeneration occurs rapidly

Estrogen receptor gains the ability to activate transcription through an activation pathway, in which ligand binding, phosphorylation, interaction with coactivators and corepressors, and binding to the estrogen response element all contribute to the receptors activation potential. The estrogen response element, or ERE is a kind of allosteric effector, regulating receptor conformation.

Days 1-5 Menstrual Phase: uterus sheds majority of endometrium Ovarian hormones at lowest point, GnRH begin to rise Menses = Detached tissue and blood pass out through vagina as menstrual flow
Plasmin inhibits clotting

Days 6-14, Proliferative (preovulatory) phase

Endometrium rebuilds itself under influence of rising estrogen levels Follicular phase
FSH has been stimulating the growth of follicles & 5-7 compete for entry into the mestrual cycle - they have been growing for the better part of a year in a process known as folliculogenesis LH causes estradiol to be released by the follicles, this inhibits release of FSH As more estrogen is secreted, more LH receptors are made by the theca cells, inciting theca cells to create more androgen that will become estrogen downstream. Positive feedback - loop causes LH to spike sharply Inhibin released by largest follicle

Prostaglandin level is high in menstrual blood causing contractions of uterine wall to speed rate of blood and tissue loss By day 5, Growing ovarian follicles start to produce more estrogen

Estrogens also:
induce proliferative endometrium induce synthesis of progesterone receptors in endometrial cells

Cervical mucus thins forming channels for sperm passage

Recruitment activation of primordial follicle into a primary follicle Secondary follicle has FSH receptors, theca cells with LH receptors Graffian follicle = mature follicle, antral follicle Corpus luteum = ruptured follicle

Day 14: Ovulation occurs at the end of this stage in response to sudden surge of LH Dominant follicle = 2 cm & has LH receptors
Nuclear membrane around oocyte breaks down, MI completes (secondary oocyte) LH causes lutenization of granulosa cells

Days 15-28 Secretory (postovulatory) phase Endometrium prepares for implantation of an embryo Rising levels of progesterone from corpus luteum act on endometrium causing changes
Converts the proliferative endometrium into a secretory lining receptive for implantation and support of the early pregnancy

Ruptured follicle now converted to a corpus luteum granulosa enlarge


the corpus luteum will produce progesterone in addition to estrogens for approximately the next 2 weeks.

Prostaglandin produced by endometrium stimulated by LH stimulates muscle contraction to propel egg down oviducts Egg survival 12 to 24 hours post ovulation if fertilized, will implant ~ day 19

Cervical mucus becomes viscous, forming the cervical plug Increased progesterone & estrogen inhibit LH release

IF fertilization occurs Zygote will travel as an early embryo through the tube to the uterine cavity and implant itself 6 to 12 days after ovulation. Shortly after implantation, the growing embryo releases human chorionic gonadotropin (hCG), to signal its existence to the maternal system. hCG Used in pregnancy tests Role = hCG signal maintains the corpus luteum and enables it to continue to produce progesterone
Mean sperm survival = 4 days Ovum survival = 2 days Pregnancy window = 7 days (5 days pre ovulation to 2 days post ovulation)

No fertilization corpus luteum begins to degenerate towards the end of this phase Progesterone levels fall Days 24-28, Premenstrual phase
Rapid decline in progesterone & estradiol Disintegration of corpus luteum and endometrium

Degeneration of endometrium
Spiral arteries kink and spasm Lysosomes rupture, functional layer begins to self-digest Day 28 menstruation begins

phases Day 1 follicular phase

SOURCE

HORMONE

TARGET

EFFECT on OVARIAN CYCLE stimulates anterior pituitary to release LH & FSH stimulates follicle growth and maturation, stimulates ESTROGEN secretion stimulates thecal cells to produce ESTROGEN 1) small levels - inhibits release of LH & FSH, stimulates production and accumulation of LH & FSH. 2) high levels cause surge of LH & FSH to be released

EFFECT on MENSTRUAL CYCLE

phases Day 1 menstrual phase

HYPOTHALAMUS

GnRH

PITUITARY

PITUITARY PITUITARY

FSH LH

FOLLICLES Theca Cells (initially)

FOLLICLE & THECA CELLS GRANULOSA CELLS

ESTROGENS

PITUITARY

stimulates rebuilding of endometrium, induces synthesis of progesterone receptors in endometrial cells; causes thinning of cervical mucous

Day 5 proliferativ e phase

INHIBIN

PITUITARY

inhibits release of FSH stimulates completion of MI forming secondary oocyte that goes on to MII, triggers ovulation. Causes change into corpus luteum & stimulates it to produce protgesterone and estrogen acts on the endometrial cells, causing elaboration of spiral arteries; causes cervical mucus to become viscous

Day 14 ovulation

PITUITARY

LH

Primary Oocyte (dominant follicle)

Day 14 secretory phase

luteal phase

CORPUS LUTEUM

PROGESTERONE

PITUITARY

inhibits release of FSH & LH