Female Reproductive SystemDr. Christine AyochokJanuary 22 & 24, 2013

Components:1. Ovaries: Female gonads Contain ovarian follicles (produce estrogen) that promote development of ova Corpus Luteum Follicle remnants after ovulation Provide estrogen and progesterone2. Uterine Tubes (Oviducts): Capture released ovum Primary site for fertilization Convey ovum to the uterus3. Uterus: hollow muscular organ lined by mucous (endometrium) that undergoes cyclic changes controlled by ovarian hormones4. Vagina Tubular organ that directs spermatozoa to cervical canal Vaginal fluid: increases sperm motility Estrogen: causes epithelium to thicken and its cells to accumulate glycogen5. External genitalia: numerous nerve endings: sexual arousal (Clitoris, Labia Majora and Minora)

Cyclic Changes Roughly every 28 days between menarche and menopause Changes in structures and activity of each organ, especially ovaries and uterus Synchronization Crucial to normal reproductive function Pituitary FSH and LH that directly modulate follicle growth and development, and ovarian hormone production Ovarian hormones (estrogen, progesterone): control changes in uterine lining and influence FSH and LH through negative feedback

OVARIESGeneral Organization Yellow white in color Paired, almond-shaped orangs (3 x 1.5. x 1 cm) Germinal epithelium Outer covering Does not form oocytes (because it is located in the oocyte) Simple cuboidal epithelium derived from peritoneum Tunica Albuginea Inner covering Dense CT capsule between germinal epithelium and cortex Peripheral cortex: harbors most of oocyte-containing ovarian follicles embedded in a stroma Central medulla: stroma containing rich vascular bed

Ovarian follicles Each with a single oocyte surrounded by 1 or more layers of follicle (granulosa cells) Cortex Follicles at various stage of development Primordial, growing, mature, atreticPrimordial follicles Inactive: earliest stage of follicle development Predominant follicles present before puberty, still constitute the majority thereafter Each consists of a primary oocyte (most in diplotene stage of meiosis I prophase) surrounded by 1 layer of squamous follicle cells; flattened Oocyte Up to 26 u in diameter Pale, eccentrically placed nucleus with conspicuous nucleolus

Growing Follicles Growth stimulated by FSH Oocyte enlarges to 125 to 150 u Follicle epithelium becomes cuboidal and proliferates to become stratified (multilaminar) Stromal tissue surrounding follicle: differentiates into steroid hormone-producing theca folliculi Primary follicles Primary oocyte surrounded by single or multiple layers of cuboidal follicle cells No antrum Unilaminar Single layer of cuboidal cells Glycoprotein-rich zona pellicud forms between oocyte and follicle cells Multilaminar Multiple layers of follicle cells Zona pellucida thickens Theca folliculi forms Steroid secreting, coming from the stroma

Secondary follicles Cavities filled with fluid (liquor folliculi) appear between the follicle cells, gradually coalescing to form 1 large cavity or antrum Theca folliculi forms 2 layers Theca interna: rich vascular network and steroid secreting cuboidal cells with abundant SER Theca externa: mainly vascular connective tissue

Mature (Graafian) Follicles Large diameter (2.5 cm) Immediately precedes ovulation Antrum size increases greatly Oocyte displaced to one side of the follicle, surrounded by a few layers of follicle cells (corona radiate) Oocyte rests on a pedestal of follicle cells (cumulus oophorus) Atretic Follicles 400,000 follicles present at birth 450 develop to maturity, more than 99% become atretic Atresia of primordial follicles Leaves a space filled by stroma Primary and secondary follicles Remnants removed by macrophages and replaced by stromal cells, with collagenous scar Scar gradually removed and remodeled into normal stromal tissue

Origin and Maturation of Oocytes Embryo Yolk sac endoderm gives rise to primordial cells that migrate to the genital ridges in posterior wall of abdominal cavity Germ cells Surrounded by flattened follicle cells Enter 1st meiotic division and arrest at prophase (primary oocytes) 1st meiotic division completed before ovulation (secondary oocytes) Ovum: secondary oocyte with almost all of the cytoplasm Other: 1st polar body Ovum begins meiosis II before ovulation, halts in metaphase until fertilization occurs Fertilization: meiosis II completed, with formation of 2nd polar body Zygote: fertilized ovum Polar body will disintegrate thereafter

Ovulation Day 14 of a 28-day cycle Rupture o f a mature follicle and release of its ovum Preceded and stimulated by a surge in LH Ovum + zona pellucid + corona radiate detach from cumulus oophorus and float in antrum Collagenase: stroma thins and becomes ischemic between follicle and ovary surface, indicating site of imminent rupture (stigma) Rupture: ovum + corona radiata intact expelled by ovary and captured by uterine tube Ovum degenerates unless fertilized within 24 hours

Corpus Luteum Temporary endocrine gland Formed by remnants of follicle after ovulation Cells in granulosa cell layer and theca interna enlarge and secrete steroid Granulosa lutein cells: large, pale-staining, estrogen-secreting, derived from theca interna Corpus luteum of Menstruation Fertilization does not occur Degenerates after about 14 days Corpus luteum of Pregnancy Enlarges and maintained for 6 months, gradually declines thereafter and persists until the end of pregnancy Secretes estrogen, progesterone Secretes relaxin Polypeptide hormone that loses fibrocartilage Attachment of Symphysis pubis, allowing pelvic opening to enlarge during parturition Depo provera, inhibits LH surge Breast feeding, inhibits LH surge via increased Prolactin

Corpus albicans Dense CT scar Replaces a degenerated corpus luteum Eventually removed by macrophages Albicans (whitish in color) will eventually be replaced by stromal tissue

Hormones and Ovarian Function FSH: stimulates follicle growth during 1st half of menstrual cycle Growing follicles produce estrogen, whose high mid-cycle levesl puts negative feedback on pituitary gland thereby reducing FSH Decreased FSH causes LH surge that directs follicle maturation, stimulates ovulation, control and maintenance of corpus luteum Corpus luteum: produces both estrogen and progesterone Progesterone inhibits LH production, causing corpus luteum to degenerate after about 14 days (without fertilization) With fertilization Chorionic gonadotropin produced by developing placenta maintains corpus luteum in the absence of LH

Sympathicotropic Cells (Burger Cells) Always aksed in practicals, located in the hilum Hilum Secrete testosterone Epithelioid cells with clear cytoplasm Central dark-staining nucleus Seen as clusters

Vestigeal Organs associated with the Ovary Parallel or diverging tubules in Mesovarium, extending from hilus of ovary toward oviduct and fuses with longitudinal tubule parallel to oviduct, lined by cuboidal epithelium 4 vestigeal organs, name depends on its location:1. Hydatid Cyst of Morgagni: cyst-like expansion of the upper end of the longitudinal tubule2. Duct of Gartner: opposite end of longitudinal tubule extending some distance to uterus3. Epophoron Transverse tubules and longitudinal duct of Gartner Rudiment of nephrosis Homolog of ductuli efferents and epididymis in males4. Paraophoron Vestigial epithelium lined tubules in braid ligament between epoophoron and uterus Remnant of caudal portion of mesonephron, homologous to vestigial paradidymis in males Clinical Correlation: normally seen intraoperatively

UTERINE TUBES 12 cm long muscular tubes Lumen continuous with uterine cavity Distal end opens to peritoneal cavity near ovary Function Captures ovulated ovum Provides suitable environment (most common site of) for fertilization Transports zygote to uterus

Segments Pars interstitialis (intramural) Penetrates uterine wall Fewest mucosal folds Most proximal Isthmus Narrower segment adjacent to uterine wall Common site of ectopic pregnancy Ampulla Widest segment Common site for fertilization Extensive branched mucosal folds Infundibulum Funnel-shaped distal segment Fimbriae: finger-like extensions of mucosal folds

Wall structure 3 layers: Mucosa, Muscularis, Serosa No Submucosa infection easily spreads in the Muscularis Mucosa Lining epithelium Lamina Propria Mucosal folds Largest and most numerous in the ampulla, infundibulum Lining Simple columnar with 2 cell types Ciliated columnar cells: most of cells beat towards the uterus, thus aiding in egg transport Peg cells Shorter, mucus-secreting Secretions helps transport the ovum and hinders bacterial access to peritoneal cavity Muscularis Inner circular, outer longitudinal smooth muscle layers Contractions move the ovum toward the uterus Serosa Outer covering of visceral peritoneum

Cyclic Changes Most marked on fimbriae, infundibulum and upper ampulla Diminish toward the isthmus Follicular phase Epithelial cells enlarge and begin ciliogenesis Increased activity of peg cells Peak at midcycle Reversed in the luteal phase Example Preovulatory phase Percentage of ciliated cells in the fimbriae 48%, decreased to 4% in the luteal phase

UTERUS Pear-shaped muscular organ in pelvic cavity Site of embryonic implantation and development Gross: 3 regions Body (corpus): large, round, middle region Fundus: part of the body above the entry of the uterine tubes Neck (cervix): narrow, downward extension of uterus into vagina Wall: 3 layers Endometrium Myometrium Serosa or Adventitia

Endometrium Uterine mucosa Simple columnar epithelium supported by lamina Propria Dual blood supply From Arcuate arteries (branch of uterine artery) Straight arteries to basale (retained during shedding) Coiled arteries to functionale (lost during shedding) 2 layers: Stratum functionale Pars functionalis Temporary layer at luminal surface Responds to ovarian hormones by undergoing cycling, thickening and shedding Zona compacta (near lumen) and deeper zona spongiosa Stratum basale Pars Basalis Thinner, deeper, zona spongiosa Contains basal portions of endometrial glands Retained during menstruationMyometrium Most conspicuous Thickest tunic of uterus 4 poorly defined smooth muscle layers Middle layers: contain Arcuate arteries Pregnancy: myometrium grows via hypertrophy (size) and hyperplasia (number) to contain growing fetus At birth Oxytocin stage: promotes forceful myometrial contractions that expel fetus

Serosa Covers fundus and most of the body

Menstrual Cycle 3 phases based on structural and functional changes in endometrium1. Menstrual 1st day of menses to days 3-5 of cycle Ischemia, degeneration, shedding of functionalis Fragments of functionalis tissue along with blood and uterine fluid are discharged through vagina as menstrual fluid2. Proliferative (follicular phase Days 4 to 6 to day 14 of cycle Under influence of estrogen: endometrium regenerates from basale Functionale thickens, glands lengthen and remain straight *Follicular refers to ovary *Proliferative refers to endometrium3. Secretory (Luteal) phase Days 15 to 28 of cycle Progesterone: edema of lamina Propria, endometrial thickening Glands: highly coiled, saw-tooth appearance Day 20: prepared to receive implanting embryo Without implantation: cycle begins

Uterine Cervix Inferior part of uterus External surfaces bulges into vaginal canal Wall Mainly dense connective tissue Small amount of smooth muscle Mucosa Tall columnar epithelium (ciliated simple columnar) Branched cervical glands: penetrate lamina Propria Stratified squamous epithelium: external (vaginal) surface External os Switch to epithelial type Not shed during menstruation Ovulation: watery secretions permit access by sperm Luteal phase and pregnancy: Secretions abundant and more viscous Preceding parturition: cervical dilatation in response to collagenase activity in cervical wall Clinical correlation: Internal examination cervix is measured

Fertilization Ampullaroisthmic junction Sperm penetrate corona radiate and zona pellucida 1 sperm head fuses with oolemma Induces completion of ovums meiosis II Haploid male and female pronuclei: zygote Zygote: several rounds of mitosis: morula Cavity in embryo: blastocyst: enters uterus (day 4) Blastomeres: 2 layers: peripheral trophoblast and inner cell mass Floats 2 to 3 days before implantation (zona pellucida dissipates to allow trophoblast cells to be in direct contact with endometrium)

Implantation Penetration of uterine epithelium by blastocyst 1st step in placentation Blastocyst activity Trophoblast cells divide rapidly, differentiate into 2 layers Syncytiotrophoblast Highly invasive outer layer, multiple nuclei in a single large cytoplasm Formed by fusion of mononucleated cells from underlying layer (cytotrophoblast) Day 9: embryo completely embedded in endometrium, surrounded by trophoblastic cells Inner cell forms bilaminar disk (blastodisk) that becomes the embryo with a shell of extraembryonic mesoderm In between: extraembryonic coelom Embryo separated from endometrium by colon Chorion Includes derivatives of trophoblast and extra embryonic mesoderm: 2 regions Chorion frondosum Lies adjacent to decidua basalis Forms fetal part of placenta Chorion laeve Adjacent to decidua capsularis Fuses with decidua parietalis midway through pregnancy Decidual reaction Decidua: pregnant endometrium Endometrial changes: decidual reaction: helps prevent invasion of trophoblast beyond endometrium (decidua increta /percreta) Stromal cells enlarge to become decidual cells (prolactin) 3 layers of decidua: Decidua basalis: underlies implantation site, forms maternal part of placenta Decidua capsularis: overlies implanted embryo, separating it from uterine cavity Decidua parietalis / vera: remainder of endometrium

PLACENTA Has embryonic (corpus frondosum) and extraembryonic (decidua basalis) components Steps in placental development (placentation) Syncytiotroph surrounds small islands of endometrium that contain blood vessels Enzymes lyse maternal tissue, leaving lacunae and rupturing blood vessels Blood vessels fill syncytiotroph-lined lacunae Chorionic villi grow into these lacunae Chorionic villi Bring blood in fetal blood vessels close enough to maternal blood in lacunae for exchange Selectively permeable placental border Definitive evidence for pregnancy than the decidua

Placentation Primary villi: tongues of cyto and syncytiotroph Secondary villi: syncytio, cytotroph, core of extraembryonic mesenchyme (become blood vessels that establish connections with umbilical vessels of fetus and maternal circulation) Tertiary villi: syncytio, cytotroph, entraembryonic mesenchyme with blood vessels in its course

Placental Functions Transfer of nutrients and wastes Day 23 AOG: fetal blood circulating through tertiary villi Nutrients from maternal blood (lacunae) reach fetal circulation by passing successively through the syncytiotroph, cytotroph, basal lamina of troph, extraembryonic mesenchyme, basal lamina of blood vessels in tertiary villi, fetal vascular endothelial cells Placental barrier: restricts substances crossing between 2 circulations Fimbrinoid: layer of products of necrosis that forms non-antigenic barrier Placental hormones Syncytiotroph, decidual cells Chorionic gonadotropin, chorionic thyrotropin, chorionic corticotrophin, estrogens, progesterones, prolactin, placental lactogen Cells that secrete hormone except cytotrophoblast

VAGINA Extends from the cervix to the external genitalia Walls lack glands Vaginal lubrication: secretions from cervical and Bartholins glands and smaller mucus glands in vestibule 3 layers: Mucosa, Muscularis, Adventitia Mucosa Stratified squamous epithelium rich in glycogen, elastic fiber-rich lamina Propria Low pH: lactic acid accumulation due to bacterial metabolism of glycogen Extensive capillary plexus in lamina Propria: fluid into lumen during sexual arousal! Muscularis: mainly longitudinal smooth muscle, some circular fibers near mucosa Adventitia Dense connective tissue rich in elastic fibers Extensive venous plexus, nerve fiber bundles, clusters of neurons Clue cells: indicative of bacterial vaginosis Glycogen is stained within cytoplasm, if without, indicative of malignancy or dysplasia EXTERNAL GENITALIA Richly innervated with Meissners and Pacinian corpuscles free nerve endings1. Clitoris Homolog of dorsal part of penis Surrounded by prepuce, covered stratified squamous epithelium2. Vestibule Receives vaginal and urethral openings Covered by stratified squamous epithelium 2 types of glands Bartholins glands (glandulae vestibulares majores) 2 large tubulo-alveolar mucus glands on opposite sides of vestibule Analogous to Cowpers glands in the male Vestibular glands (glandulae vestibulares minores) Smaller and more numerous mucus glands analogous to glands of Littre3. Labia minora Skin folds with core of spongy (erectile) connective tissue Covered by stratified squamous epithelium Analogous to ale corpus Spongiosum Thin keratinized layer on surface Contain sweat and sebaceous glands Lack hair4. Labia majora Folds of skin with a core of subcutaneous fat and thin layer of muscle Inner surface to that in labia minora Outer surface: numerous sebaceous and sweat glands Analogous to the scrotum in males

[Type text][Type text][Type text]