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Functional Histology of the Female Reproductive System IDr. Stany Wilfred Lobo, PhDAssociate Professor Dept. of Anatomical SciencesEmail: dr.swlobo@yahoo.com

10/30/09Urinary Tract 1Functions of Ovary Production of gametes: (oogenesis) Developing gametes are called oocytes Mature oocytes are called ova (singular: ovum)Production of hormones:Estrogens and Progestogens Growth and maturation of internal and external sex organsFemale secondary sex characteristics that develop at pubertyBreast development (ductal and stromal growth; accumulation of adipose tissue)Prepare uterus for pregnancyComposed of cortex and medullaMedulla: central partloose connective tissuelarge contorted blood vessels, lymphatics and nervesCortex: contains ovarian follicles embedded in rich cellular connective tissueScattered smooth muscle fibers are present in stroma around follicles

Ovarian Structure4

Surface of ovary is covered by single layer of cuboidal epithelium called germinal epithelium Primordial germ cells are extragonadal and migrate from embryonic yolk sac into cortex of ovaryTunica albuginea:dense connective tissue layer between germinal epithelium and cortex

Germinal epitheliumOvarian tumors5

GEtunica albunEach follicle contains a single oocyteFollicles distributed in stroma of the cortexEarly follicular stages occur during fetal life primordial germ cells migrate to the primitive gonads and differentiate to oogonia under the influence of genetic sexmitotic divisions greatly increase the number of oogonia Oogonia stop mitosis and become invested with follicular cells around 3rd month of gestationoogonia now called oocyte (invested in primordial follicle)oocytes initiate meiosis during fetal life Arrested in prophase IRemain dormant till puberty

Ovarian FolliclesPGC from yolk sac7During puberty ovaries begin reproductive processcharacterized by growth & maturation of groups of follicles in each menstrual cycleNormally, in each cycle only one oocyte reaches full maturity and is released in each cycleDuring the entire reproductive period approx. 400 mature ova are produced

Ovarian follicles contDuring fetal life 5 million oocytes producedAt birth around 40 K are present- rest are lost by ATRESIAAround 400 are used during reproductive period

Ovarian follicles contHistologically 3 developmental types of follicles PRIMORDIAL FOLLICLESGROWING FOLLICLES :Primary folliclesSecondary (ANTRAL) folliclesMATURE or GRAAFIAN FOLLICLES

Follicle DevelopmentZona pelluicida only allows 1 sperm to enter1) Prevent polyspermic2) Prevent abnormal implanatation.If zonua pelluida disaapers tubal pregancy in fertilzation tube

10PRIMORDIAL Follicles:Appear during 3rd month of fetal developmentFound in stroma of cortexSingle layer of squamous cells surrounds oocyteOuter surface of follicle cells has a basal lamina

Primordial follicle


Oocyte enlargesfollicular cells become cuboidal As oocyte grows deeply staining acidophilic layer, called ZONA PELLUCIDA, appears between follicle cells and oocyteZP acts as sperm receptor

Primary follicle15

3/24/14Ovary 200415Early primary follicle X640Rapid mitoses of follicle cells produces a stratified epitheliumMEMBRANA GRANULOSA Follicular cells are now called GRANULOSA CELLS


zona pellucidaAs granulosa cells proliferatestromal cells immediately surrounding follicle form a sheath of connective tissue THECA FOLLICULIlocated external to basal laminaPrimary follicle cont.Theca differentiated into 2 layers:THECA INTERNAinner, highly vascular layer of cuboidal secretory cellsEM appearance of steroid secreting cellsHave many LH receptorsProduces estrogen

theca internaTHECA EXTERNAouter layer of connective tissue cellsContains smooth muscle cells and bundles of collagen fibersBoundaries between externa and stroma are indistinct

Characterized by fluid-filled ANTRUMFollicle increases in size by proliferation of granulosa cellsFactors required for oocyte and follicle growth:Follicle-stimulating hormone (FSH)

Secondary FollicleCAVITY21cavity

A- antrumGc

22When granulosa layer reaches 6-12 cells thickfluid-filled cavities appear among granulosa cellsFluid called LIQUOR FOLLICULI (follicular fluid) hyaluronic acid-richCavities coalesce to form a crescent-shaped cavity-AntrumFolllicle is now a secondary (ANTRAL) follicle

Antrum contains a fluid called liquor folliculi23The eccentrically positioned oocyte reaches 125 um diameterundergoes no further growthOocyte maturation inhibitor (OMI) secreted by granulosa cells into antrumOMI level progressively decreases as oocyte maturation increasesas secondary follicles enlargeantrum also enlarges lined by granulosa cellsGranulosum is uniform at the wall of the follicleConnected to the cells of the follicle wall byCUMULUS OOPHOROUS

AGGGACumulus cells immediately surround oocyte called the CORONA RADIATAGranulosa processes increase in number correlated with increased LH receptors on antral surfaceCall-Exner BodiesSecreted by granulosa cellsPAS+ bodiesextracellular among granulosa cellsContain hyaluronic acids and proteoglycans

Mature follicle:diameter of 10mm or morecauses bulge on surface of ovaryGranulosum thins as antrum size increases

Development of Graafian Follicle

Corona radiataoccyte

1 or 2 oocytetheca internagranulaosaculumosTHECA layers become prominentLipid droplets in cytoplasmevidence for steroid secretionNormal level of LH stimulates theca interna cells to secrete Estrogens

Primary oocyte could be arrested from 12 to 50 yearsIn prophase of meiosis I first meiosis initiated during the embryonic lifeCompletion of first meiosis occurs just before ovulation (in response to LH surge)Daughter cell with most cytoplasm now called: SECONDARY OOCYTE (23 X) measures 120-150 um diameterDaughter cell with least cytoplasm first polar body (degenerates)Secondary oocyte completes Meiosis II only if fertilized

OvulationOvulation is process by which secondary oocyte is released from Graafian follicleBefore ovulation blood flow stops in area of ovary surface called macula pellucida (Stigma) Oocyte with the surrounding cumulus cells is expelledOocyte is guided to oviduct by fimbriaeOvulation cont.Only 1 follicle is selected from a cohort of follicles to undergo maturation and ovulationReleases secondary oocyteEgg is viable in the female genital tract for 24 hoursEctopic implantations might happens in the following sites:ovary surfaceintestinal surface- in both cases should be removed by surgeryAt ovulation about 45% of women experience midcycle sharp lower abdominal painRelated to smooth muscle cell contraction in the ovarysurge of LH

Ovulation cont.Occurs in ampulla of oviductFew hundred sperm (out of few millions) reach oviduct ampullaSperms undergo CAPACITATION- an activation process that leads to vigorous motility- involve several biochemical changes and modification to sperm plasma membrane Capacitated sperm makes its way through corona radiata cellsNext, sperm binds to zona pellucida Triggers ACROSOME REACTIONacrosome enzymes released sperm then penetrates zona pellucida and its membrane fuses with the oocyte membranezona pellucida impermeable to other sperms

FertilizationFusion of the membranes triggers resumption of meiosis II - secondary oocyte expels 2nd polar body and becomes mature ovum ( 23 X) - DNA forms maternal pronucleusSperm penetrates mature ovum - DNA forms male pronucleus

Fusion of the male and female pronuclei forms a ZYGOTE (46)Fertilization cont.After ovulation the rest of the follicle differentiate into new functional unit, the CORPUS LUTEUMformed from granulosa and theca interna cellsFirst Filled with blood from veins of theca internacalled CORPUS HEMORRHAGICUMThen reorganizes into corpus luteumLuteal cells increase in size are filled with lipid droplets

Corpus LuteumAfter successful fertilization and implantation, corpus luteum secrete MAINLY progesteroneDepends for existence on luteotropins mainly human chorionic gonadotropin (hCG) initially produced by the embryo and later by the placenta

Corpus Luteum of PregnancyIf fertilization and implantation do not occur corpus luteum will remain active ONLY for 14 daysThis is called CORPUS LUTEUM OF MENSTRUATIONDegenerates and involutesCorpus ALBICANSInactive white scar formed as intercellular hyaline and collagenous material accumulates among degenerating cellswill disappear after several months

Corpus Luteum of Menstruation