Oogenesis & Ovulation

Menstrual CycleOvarian CycleOogenesis, Folliculogenesis, Ovulation, Formation of the Corpus LuteumJohn T. TranOogenesis:Goal: to produce haploid gametes oocytesUnlike sperm, which is designed for motility, oocytes must carry all factors that initiate developmentPrimordial germ cells (PGCs) undergo mitosis in uteroBecome oogoniaEnter the meiotic prophase I, stall as diplotene as 1o oocytesProgression of meiosis is blocked by meiotic inhibitory factor produced by follicle cellsNucleus of dormant 1o oocytes enlarges and is called a germinal vesicleWhat do you guys think is the role of the germinal vesicle?

Oogenesis:Where do PGCs come from?PGCs migrates from the yolk sac to the gonadal ridge (derived from what mesoderm?)By 7th month in utero, most oogonia have transformed into primary oocytes. Most primary oocytes are degenerated thru a process called follicular atresiaBy puberty, both ovaries contain about 300,000 oocytesDuring the reproductive life of a woman (30-40 years), only about 450 oocytes are ovulated. The rest undergo atresiaStages of meiosis

In Prophase I:Pachytene: crossing over occurs between homologous chromosomesDiplotene: chromosomes begin to separateDiakinesis: tetrads start moving to the metaphase plate, nuclear envelope breaks downOverview of uterine and ovarian anatomy

FolliculogenesisOverview

When the primary oocytes are formed, each become surrounded by simple squamous epithelial cells primary oocytes + follicular cells = primordial follicle

Folliculogenesis

During each menstrual cycle, a small number of primordial follicles grow and the follicular cells change from simple squamous to simple cuboidal unilaminar primary folliclesNot hormone dependentZona pellucida glycoprotein layer produced by follicle cells and oocyte

Folliculogenesis

Continued proliferation of follicular cells forms stratified follicular epithelium, the granulosaFollicular cells are now called granulosa cellsThe follicle is a multilaminar primary follicle

Within the zona pellucida, ZP3 and ZP4 are important sperm receptors which induce acrosomal activation

Folliculogenesis

Under influence of FSH and LH, epithelium further proliferates and becomes multilayered secondary follicle

Few of these follicles will proceed thru oogenesis

Sources differ on how they differentiate between secondary follicles and multilaminar primary follicle OR between secondary follicles and antral follicles

Folliculogenesis

Secondary follicles that develop a fluid-filled cavity, called the antrum antral folliclesThe ovarian tissue surrounding the entire follicle differentiates into 2 CT layers:Theca interna inner layer: blood vessels, secretes 2 androgensAndrostenedione, converted to estradiol by aromatase regulated by FSHTestosterone, converted to estrogen by aromatase regulated by LHAromatase is located in the granulosa cellsTheca externa outer layer: smooth muscles

One of the growing follicles becomes dominant over the rest of the developing follicles (process unknown)Dominant follicle reaches the most developed stage of follicular growth and undergoes ovulationThe other antral follicles undergo atresiaFolliculogenesis

Late antral follicle with some new structuresMuch larger antrum (A), contains follicular fluidHyaluronate, growth factors, plasminogen, fibrinogen, anticoagulant heparin sulfate proteoglycan, and high concentrations of steroids (progesterone, androstenedione, and estrogens)Notice that the oocyte (O) projects into the antrumGranulosa cells surrounding this occyte are termed corona radiata (CR)CR communicates with oocyte via gap junctions between processes that cross the zona pellucidaCorona radiate and oocyte attach to the side of the follicle via the cumulus oophorus (CO), which is continuous with the remaining granulosa cells

Folliculogenesis

Most developed stage of folliculogenesis prior to ovulation Graafian follicle (or mature or preovulatory)Antrum increases greatly in sizeThick thecal layers

Folliculogenesis

Important: All this time the oocyte has not yet restarted meiosis, its still a primary oocyte arrested at Prophase I (diplotene)Lets take a quick break

Menstrual cycleComposes of the ovarian cycle + uterine cycleMade up of 3 phases: menstrual (1-5 days), proliferative (8-10 days), & secretory (ovulation ~ 14 days)

Menstrual cycle Menstrual Phase (Day 1-5):Sloughing of the endometrium from the previous cycleFirst day of menstrual cycle = first day of bleedingDay 5, small numbers of responding follicles begin to produce estrogenCauses uterine endometrial lining to proliferate, initiating the next phase

Supplementary pdf, page 3Menstrual cycle Proliferative Phase (Day 5-15):Hypothalamus secretes GnRHsPituitary gland produces:FSH maturing follicles continue to developLH follicle cells signal to the oocyte to restart meiosisFSH + LH cause thecal and follicle cells to produce estrogenEndometrium proliferates, cervical mucus thins so sperm can enter uterusEstrogen secretion peaks ~ day 14Causes burst of GnRH burst of FSH & LH (ovulatory surge) which causes ovulation!

OvulationRecount from folliculogenesis, we are now at the last stage, Graafian follicleOocyte resumes and completes the first meiotic divisionChromosome equally divided between 2 daughter cells but 1 daughter cells retains almost all the cytoplasm secondary oocyteThe other becomes the 1st polar bodyNucleus of oocyte begins second meiotic division but arrests at metaphase II, never completes meiosis unless fertilization occurs!

Supplementary pdf, page 2. Some discrepancies exist, but sources differ.

Menstrual cycle Secretory (Luteal) Phase (Day 15-28):After ovulation, granulosa cells and theca reorganize to form a larger endocrine gland, the corpus luteumLuteal cells secretes progesterone, which maintains uterine wall for implantationThecal cells (theca interna) secretes estrogenLuteal cells also secretes inhibin turns off FSH production, preventing any more follicles from maturing

If fertilization does not occur, corpus luteum degenerates to a scar of dense CT called corpus albicans

If fertilization occurs, trophoblast cells of embryo secretes a hormone, human chorionic gonadotropin (hCG), which maintains the corpus luteum so that progesterone levels stay high (Supplementary pdf page 6)Corpus Luteum

Corpus albicans

For.Your. Viewing. Pleasure.

Menstrual cycle

ReferencesUIC BIOS 325 Vertebrate embryology lectureDr. Taos lecture on Female Reproductive SystemMescher, Anthony L. "Junqueira's Basic Histology: Text & Atlas , by Anthony L. Mescher." (2013).