IN THE NAME OF GOD THE COMPASSIONATE THE MERCIFUL Histology Female Reproductive System Female reproductive system comprises of following organs: • Ovaries , Oviducts , Uterus , Vagina , External Genitalia Ovary •Small, almond shaped organs, lying in pelvic cavities •Germinal epithelium is surface epithelium: simple cuboidal •Tunica albuginea: dense irregular CT is directly beneath epithelium •Ovary has two components: cortex + medulla Cortex •Cortex has two components: stroma + structures that producing gametes •Cortical stroma: closely packed spindle shaped fibroblast-like cells (arranged in a whorled pattern) + collagen fibers between stromal cells (prominent in outer cortex, with time amount of collagen will increase) Medulla •Medulla contains loose CT + vessels + remnants of Wollfian ducts irregular tubules lined by a cuboidal epithelium •Hilum is whereby vessels and nerves enter and leave ovary •Hilus cells: identical to Leydig cells, may contain Reinke’s crystalloids, often found near blood vessels (small clumps ) •Medulla contains stromal cells identical to those which are in the cortex Cortex •Stroma provides structural support + forms theca interna and externa around follicles + secretes steroid hormone •Three types of stromal steroid secreting cells: •Scattered luteinized stromal cells which are numerous during pregnancy •Stromal cells that form theca layers •Enzymically active stromal cells (EASC)which are numerous in postmenopausal women and secret testosterone Ovarian follicles •Ovarian follicles located in cortex and surrounded by stromal cells •A follicle consists of an oocyte surrounded by one or more layers of follicular cells •2 ovaries of young adult female have about 400,000 follicles; most of them will degenerate (atresia) •About 450 follicles will cycle to ovulation in lifetime Types of Ovarian Follicles •Based on morphological characteristic follicles can be categorized into: •Primordial Follicles •Growing Follicles –Unilaminar primary follicles –Multilaminar primary follicles –Secondary follicles •Mature Follicles (Tertiary or Graafian Follicles) Primordial follicles •Primordial follicles contain: a primary oocyte (in prophase of first mitotic division) surrounded with one layer of flattened follicular cells, separated by a basal lamina from stroma •Most numerous in fetus (several million), One million at birth, At the onset of of buberty their number reduced to about a quarter of a million •Many of them degenerate during lifetime •Oocyte about 25 µm diameter + euchromatic nucleus + large nucleolus Growing Follicles •Oocyte diameter increases to 100 to 150 µm , Nucleus enlarges and called Germinal vesicle •Organelles increase (mitochondria, several golgi complexes, RER, free ribosomes) •Follicular cells become cuboidal •Unilaminar primary follicle has one layer of cuboidal follicular cells •Multilaminar primary follicle has several layers of follicular (granulosa) cells •Zona pellucida secreted by oocyte, is composed of 3 glycoproteins: ZP1, ZP2, ZP3, forms just outside oocyte membrane, thick basal lamina •Follicle cell filopodia + oocyte microvilli extend into Zona pellucida , joined by gap junctions •Stromal cells differentiate into theca folliculi that has a theca interna and theca externa •A thickened basal lamina separated theca interna from granulosa cells • Theca Interna: Cells are more cuboidal with round nuclei, steroid producing cell features, SER, mitochondria with tubular cristae and lipid droplets, produce andro-stenedione which is converted to estradiol by granulosa cells, highly vascularized • Theca externa: Composed of CT + stromal cells with vessels forming a plexus, cells are flattened Secondary Follicles •Granulosa and theca cells increased •Fluid-filled spaces in granulosa layer fuse to form the antrum that become filled with liquor folliculi, •Liquor folliculi is an exudates of plasma contains: GAGs + proteoglycans + steroid binding protein produced by granulosa cells +some hormones •Cumulus oophorus: a small group of granulosa cells surround primary oocyte and project into antrum •Corona radiata: a single layer of granulosa cells that immediately surround primary oocyte •Most of follicle at this stage become atretic, some granulosa cells of atretic follicles do not degenerate and form interstitial glands which secret androgens Mature (Graafian) Follicles •Mature follicle develops due to continued proliferation of granulosa cells and production of more liquor folliculi which undergo ovulation •By the time of ovulation it may be over 2.5 cm in diameter, bulge from ovary surface •Because of continued formation of liquor folliculi cumulus oophorus detaches and float freely in liquor folliculi Oocyte Meiotic Divisions • First meiotic division occurs just prior to ovulation under the influence of meiosis inducing factor • Second meiotic division then begins and stops at metaphase • Second meiotic division is completed after fertilization Ovulation •Fluid pressure builds up until follicle ruptures due to formation of proteoglycans + hyaluronic acid + attraction of water •Before ovulation, surface of ovary loses its blood supply just where the follicle pressing it and known as Stigma •Perifollicular connective tissue broken down by proteases •Ovum (Secondary oocyte) drawn into open end of oviduct •Ovum remains viable about 24 hours after ovulation •Remnants of graafian follicle are converted to corpus hemorrhagicum Corpus Hemorrhagicum • Following ovulation the remainder of follicle collapses and some ruptured blood vessels leak into follicular cavity and forming a clot that is known as corpus hemorrhagicum Corpus Luteum •After removing the clot by phagocytes a temporary hormone secreting structure formed by granulosa cells + theca interna cells known as corpus luteum •Granulosa cells hypertrophy into large pale staining granulosa-lutein cells (with organelles necessary for steroid production) •They constitute about 80% of the cells of corpus luteum •These cells produce progesterone + convert androgen produced by theca-lutein cells into estrogens • Theca interna cells form theca-lutein cells, smaller and darker staining than granulosa-lutein cells • Located in folds of cells, in perimeter of corpus luteum, form about 20% of cells population, highly vascularized • Produce estrogen, progesterone + androgens • If pregnancy does not occur corpus luteum of mensturation survives only 10-14 days • In pregnancy it enlarges greatly due to hCG and lasts 6 months and called corpus luteum of pregnancy, grows to a 5 cm diameter structure Corpus Albicans •When corpus luteum degenerate, it is invaded by fibroblasts which manufacture collagen type I and form a fibrous structure •Large ones form after pregnancy and smaller ones after each ovulation •On the surface of ovary remnants of corpus albicans is visible as a scar Atretic Follicle & Corpus Fibrosoum • Atresia is degeneration of follicles that can occur at any stage of development • Common just after birth (loss of maternal hormones), puberty and pregnancy • Nucleus of the oocyte becomes pyknotic, zona pellucida dissolves, follicular cells disperse and degenerate, and basal lamina hyalinization • Phagocytes take up dead cells fragments • In small follicle follicular cells replaced by stromal cells, no scar • When a large follicle undergoes atresia a collagenous scar may form which resemble a small corpus albican and known as corpus fibrosoum Oviduct • Uterine tube is a muscular tube, 12 cm long, upper end opens into peritoneal cavity near ovary, lower end passes through the uterus wall, It is site of fertilization • Oviduct has 4 segments – intramural part in uterine wall – isthmus is adjacent to uterine wall – ampulla is dilated part – infundibulum is funnel-shaped part near ovary with fimbriae Oviduct • Mucosa has many longitudinal folds, pronounced in ampulla • Simple columnar epit. consist of ciliated cell + nonciliated peg cell • Ciliated cells are numerous near ovarian end of tube, cilia near ovary beat toward uterus but cilia near uterus beat toward ovary • Peg cells are secretory cells, produce a watery tubal fluid contains : normal serum proteins + chloride + potassium ions • Lamina propria composed of loose CT • Muscularis consists of: poorly defined Inner circular + outer longitudinal layer of smooth muscle cells • Muscularis peristaltic movements with beating of cilia of epithelium help to propel oocyte to uterus • Serosa is a CT layer lined by a simple squamous epithelium contains blood vessels + nerves Uterus • A pear-shaped structure attached to oviducts at upper end and to vagina at lower end • Uterus is divided into three regions: Body + Fundus + Cervix • Wall of body and fundus has 3 layers: Endometrium, Myometrium, Adventitia (Serosa) •Anterior portion of body covered by adventitia, composed of areolar CT •Remaining portion of uterus covered by serosa composed of a layer of simple squamous cells (mesothelium) resting on an areolar CT Myometrium •Myometrium is the thickest layer, composed of 4 poorly defined layers of smooth muscle separated by CT •Inner and outer layers are mostly longitudinal •Middle layers are highly vascularized and consist of mostly circularly arranged bundle of smooth muscle cells •Arcuate arteries located in this layers and is known as Stratum Vasculare •Middle layers thicken during pregnancy with more and large smooth muscle cells (hyperplasia and hypertrophy) and increased collagen fibers •Myometrium is estrogen dependent in absent of estrogen smooth muscle cell atrophies and some of them begin to