Female Reproductive System

BIO 408

Histology

Dr. D. L. Daley

Ovaries

n Paired & located within the pelvis - almond shaped - 3cm long & 1.5 to 2 cm wide and 1 cm thick

n Suspended in the broad ligament of the uterus by the mesovarium (fold of the peritoneum with blood vessels)

Ovaries

n Surface - germinal epithelium (modified peritoneum) - cuboidal epithelium - does not give rise to the germ cells

n Tunica albuginea - below epithelium - dense irregular collagenous CT

n Each ovary has a highly cellular cortex and medulla

Ovarian Cortex

n Composed of connective tissue framework, stroma - housing fibroblast-like stromal cells & ovarian follicles in various stages of development

n Oogonia - primordial germ cells originate in the yolk sac & during the 6th week after fertilization migrate to the germinal ridges to populate the cortex of the developing ovaries

n Undergo mitotic divisions until near the end of the 5th fetal month - number about 5-7 million

Ovarian Cortex

n 1 million oogonia are surrounded by follicular cells and survive to the time of birth

n The remainder of the oogonia undergo atresia (degenerate & die)

n The surviving oogonia - Primary oocytes & enter prophase I & then arrested in the diplotene stage by meiosis preventing substance

n Primary oocytes remain here until just before ovulation

Ovarian Cortex

n Of the 1 million oogonia that become incorporated into follicles only about 400,000 survive to menarche (first menstrual flow (at an average age of 12.7 years)

n Typically ovulation occurs every 28 days for the next 30 to 40 years (one oocyte released each month - 450 total oocyes released)

Ovarian Follicles

n Consists of primary oocyte & associated follicular cells - arranged in a single spherical layer or several concentric layers around the primary oocyte

n Four identifiable stages of follicular development

n Primordial follicles

n Unilaminar & multilaminar primary follicles

n Secondary follicles

n Graafian follicles

Primordial Follicles

n Most primitive follicles - abundant before birth & then decline in number

n Composed of primary oocyte & surrounded by single layer of flattened follicular cells

Primary Follicles

n From primordial follicles

n Primary oocyte grows to about 100 to 150 mm in diameter - see enlarged nucleus

n Called germinal vesicle

n Follicular cells become cuboidal

n Maybe unilaminar or multilaminar

n Cells called granulosa cells

n Activin - signaling molecule made by oocyte stimulates granulosa cell activity

n Zona pellucida - amorphous substance appears that separates the oocyte from surrounding follicular cells

Primary Follicles

n Stromal cells begin to organize around the multilaminar primary follicle - forming a inner theca interna (vascularized)

n Rich in LH receptors - become steroid producing cells

n These cells produce androstenedione - enters granulosa cells and is converted into estradiol by aromatase

n The theca externa also forms - fibrous connective tissue

Secondary (Antral) Follicles

n Multilaminar primary follicles continue to enlarge - 200mm

n Thus a large spherical follicle forms with numerous layers of granulosa cells around the primary follicle

n Several intercellular spaces form within the granulosa cells & become filled with liquor folliculi - now called a secondary follicle

n FSH promotes the development of granulosa cells

n Now a clearly visible single fluid filled chamber forms - antrum

n Cumulus oophorus forms as a small group of granulosa cells extending out from follicle wall and surround the oocyte

n Single layer of granulosa cell immediately surrounding the primary oocyte is called the corona radiata

Graafian (Mature) Follicles

n Continued proliferation of granulosa cells and continued formation of liquor folliculi result in the formation of the graafian (mature) follicle

n Diameter - 2.5 cm - ovulation

n Seen as a transparent bulge in the surface of the ovary

n Follicular cells of the wall of the follicle compose the membrana granulosa

n Continues formation of liquor folliculi causes the cumulus oophorus composed of the primary oocyte, corona radiata and associated follicular cells to become detached & float free in the liquor folliculi

Ovulation

n By day 14 of the menstrual cycle, estrogen from the developing graafian follicle & secondary follicles causes elevation of blood estrogen

n This causes negative feedback inhibition of FSH & sudden surge of LH

n LH surge - increases blood flow to the ovaries & the capillaries of the theca begin leaking plasma - get edema

n Concomitant with the edema, histamine, prostaglandins & collagenase are released in the vicinity of the graafian follicle

Ovulation

n LH also causes:

n Local factor, meiosis-inducing substance to be released

n Now primary oocyte resumes & completes first meiotic division - get secondary oocyte & first polar body

n Now the secondary oocyte enters the second meiotic division & is arrested at metaphase

n The granulosa cells of the graafian follicle produce more proteoglycans & hyaluronic acid & attract more water - graafian follicle further increases in size

n The area above the graafian follicle looses its blood supply and becomes blanched - called stigma

n The stigma degenerates along with the wall of the graafian follicle - forming a opening

n Ovulation occurs through this opening & the secondary oocyte & attendant follicular cells are released

n The remnants of the graafian follicle - corpus hemorrhagicum & then the corpus luteum

Corpus Luteum

n After ovulation the remainder of the graafian follicle collapses & becomes folded

n Some ruptured blood vessels leak blood into the follicular cavity - form a central clot - called corpus hemorrhagicum

n This clot is removed by phagocytes - high levels of LH convert the corpus hemorrhagicum into the corpus luteum

n The corpus luteum is composed of granulosa-lutein cells (modified granulosa cells) & theca-lutein cells (modified theca interna cells)

Granulosa-Lutein Cells

n Granulosa cells remain in the central region of the follicle - 80% of the cell population of the corpus luteum

n These become modified into granulosa-lutein cells & produce progesterone & convert androgens produced by theca-lutein cells into estrogens

Theca-Lutein Cells

n Theca interna cells at the periphery of the corpus luteum - 20% of cell mass

n Small dark staining cells - become theca-lutein cells - specialize in the production of progesterone, some estrogens and androgens

n Progesterone & estrogens secreted by the corpus luteum inhibit the secretion of FSH & LH

n The absence of LH and FSH prevents the development of new follicles

Theca-Lutein Cells

n If pregnancy does not occur the absence of LH leads to degeneration of the corpus luteum - forms the corpus luteum of menstruation

n If pregnancy occurs human chorionic gonadotropin (hCG) is secreted by the placenta and maintains the corpus luteum for three months - now called the corpus luteum of pregnancy

Corpus Albicans

n The corpus luteum of menstruation or pregnancy is invaded by fibroblasts, becomes fibrotic and ceases to function

n It now undergoes autolysis & is phagocytized by macrophages - called luteolysis

n The fibrous connective tissue that forms in its place is called the corpus albicans & persists for some time before being absorbed

n The remnants of the corpus albicans persists as a scar on the surface of the ovary

Atretic Follicles

n Most follicles degenerate before the mature stage

n However multiple graafian follicles develop during each menstrual cycle

n Once ovulation occurs the remaining maturing follicles undergo atresia - degeneration & are phagocytized by macrophages

n These are called atretic follicles before they disappear

Ovarian Medulla

n Composed of fibroblasts loosely embedded in a collagen rich meshwork containing elastic fibers

n Also rich n blood vessels,lymph vessels and nerve fibers

n Medulla of premenstrual females has a few clusters of epithelioid interstitial cells that secrete estrogen

n Hilus cells another group of epithelioid cells that resemble Leydig cells of the testes and secrete androgens