Female reproductive system I • Oogenesis • Microscopic structure Ovarium (ovary) Tuba uterina (oviduct) Uterus Vagina Placenta and umbilical cord • Ovarian and menstrual cycle 1) Sex gland (gonad): ovarium 2) Excretory ducts: • oviduct • uterus • vagina 3) External genitalia: • clitoris • labia majoris et minoris Oogenesis • Process of formation of the oocyte, the female gamete, in ovaries • Protective structure necessary for proper ooycte nutrition, maturation and ovulation = follicle • Ovarian cycle is governed by hormones secreted by hypothalamusadepohysis and follicular cells and is linked to menstrual cycle Follicular development – ovarian cycle Important terms • Oogonia (6106 at the end of 5th month i.u.) • Primary oocyte (2106 at the end of 7th month i.u.) • Secondary oocyte immediately enters meiosis II, stop in metaphase and ovulate • Oocyte is fertilized by a sperm - meiosis II is completed, ovum forms • Zygote is formed and immediately starts to divide Meiosis I stopped at late prophase - dictyotene Meiosis I completed 48-36 hrs before ovulation Meiosis II completed after fertilization Oogonia mitotically divide 1/3 of oogonia enters meiosis I Oocyte development Spermatogenesis vs. oogeneis Ovarium - anatomy - germinative epithelium - source of folicular cells - tunica albuginea ovarii (0,05 – 0,08 mm) - cortex (folicles) - medulla (zona vasculosa, vascularisation) Ovarium (3 x 1,5 x 1 cm) • ovarial follicles: 1. primordial 2. growing: primary unilaminar, primary multilaminar, secondary 3. mature: Graafian follicle 4. atretic (degenerated) follicles • corpus luteum • corpus albicans Ovarium – important terms Primordial follicle  40 – 50 μm - oocyte  25 – 30 μm - single layer of flat folicular cells Primary folicle unilaminar  60 – 75 μm multilaminar  200 – 250 μm - oocyte  50 - 80 μm - zona pellucida (ZP) - one or more layers of folicular cells membrana granulosa (MG) - corona radiata (CR) - theca folliculi Secondary follicle  0,2 – 0,8 mm - oocyte  100 μm - ZP, MG, CR – cavities - theca folliculi interna + externa Graafian follicle  1,5 – 2,0 cm - oocyte  100 - 150 μm - ZP, MG, CR – cumulus oophorus, - antrum folliculi - theca folliculi interna + externa ? Pre-puberty Fertility Post-menopause Age-related changes in folicular development Follicular degeneration – atresia Corpus luteum Corpus luteum Corpus albicans and corpus luteum Thecalutein cells -thecal septa -Granulosalutein cells -Fibrin clot Corpus luteum Granulosalutein cells Thecal septa and thecalutein cells Ovarial stroma Hypothalamus Adenohypophysis Folicular cells GnRH FSH/LH 17β-estradiol Positive feedback Day 1-13 Progesteron Ovulation Inhibition and production of GnRH Corpus luteum i s c h e m i e Tuba uterina (tuba Fallopi, salpinx, oviduct) • Tunica mucosa – simple columnar epithelium • Cilliated cells • Noncilliated, peg cells – lamina propria • Tunica muscularis – inner circular – outer longitudinal • Tunica serosa – mesothelium – lamina propria serosae infundibulum + fimbriae ampulla - 2/3 isthmus - 1/3 pars intramuralis (pars uterina) 12-15 cm Infundibulum Fimbriae Isthmus Ampulla Tuba uterina Regional differences in oviduct histology Mucosal folds Cilliated cells Peg cells Tunica muscularis ext. Oviduct - ampulla (SEM) Tubar epithelium (TEM) Tubar epithelium (SEM) Oviduct (ampulla) - epithelium Tuba uterina - ampulla ampulla tubae uterinae X vesicula seminalis Tuba uterina – ampulla Tuba uterina – ampulla oocyte Tuba uterina - isthmus Tuba uterina - isthmus Female reproductive system I Slides 42. Ovarium (Homo, HE) 43. Ovarium (Felis domestica, HE) 44. Corpus luteum (HE) 45. Tuba uterina – pars ampullaris (HE) 46. Tuba uterina – pars isthmica (HE) Atlas EM: Primary folicle (1) Oviduct - epithelium (26, 29, 30) Female reproductive system II Uterus • Tunica mucosa (endometrium): epithelium (simple columnar), lamina propria = stroma + gll. uterinae zona functionalis zona basalis • Tunica muscularis ext. (myometrium) spiral smooth muscle fibers • Tunica serosa (perimetrium) isthmus uteri ENDOMETRIUM Zona functionalis Zona basalis Endometrium epithelium stroma Uterus (proliferation phase - gll. uterinae Myometrium Menstrual cycle • Menstrual phase (Day 1. – 4.) • Proliferative phase (Day 5. – 15.) • Secretory phase (Day 16. – 27.) • Ischemic phase (Day 28.) Hormonal regulation of ovarian and menstrual cycle • hypothalamus (nucleus arcuatus): gonadoliberin (GnRH) • hypophysis: gonadotropiny: FSH, LH • ovarium: estrogens (growing follicles, corpus luteum), progesteron (corpus luteum) • uterus Endometrium (proliferative phase): 1 – zona functionalis 2 – zona basalis Simple columnar epithelium 1 2 3-4 mm endometrium myometrium Uterus – proliferative phase Endometrium – proliferative phase epithelium zona functionalis zona basalis E N D O M E T R I U M M Y O M E T R I U M Endometrium – beginning of secretory phase Endometrium (secretory phase): 1a – pars compacta 1b – pars spongiosa zona functionalis 2 – zona basalis 1a 1b 2 Endometrium – secretory phase 5-7 mm Uterus – secretory phase Endometrium during menstrual cycle: (post)menstrual phase proliferative phase secretory phase zona basalis (1 mm) + zona functionalis (5 mm) (6 – 7 mm) pars compacta pars spongiosa Cervix uteri vagina porcio vaginalis cervicis uteri Portio vaginalis cervicis uteri Simple columnar epithelium Stratified squamous Tunica mucosa: epithelium (stratified squamous), lamina propria) Tunica muscularis ext. Spirally oriented smooth muscle tissue Tunica adventitia Vagina 1, 2 3 4 Vagina - mucosa (HE) 4 – superfitial cells 3 – intermediary cells 2 – parabasal cells 1 – basal cells Vagina – Best’s carmine (glycogen) glycogen + lactobacillus acidophilus (Döderline) -→lactic acid /pH 3.8-4/ Vaginal cytology • The vaginal epithelium is responsive to sex steroids (estrogen), and undergoes changes through the cycle in response to changes in blood estrogen concentrations. Rising levels of estrogen cause the vaginal epithelium to become "cornified" - the surface cells become large and flattened, with small or absent nuclei. • Vaginal cytology is a type of endocrine assay. Tracking changes in the morphology of desquamated vaginal epithelial cells provides a convenient means of changes in estrogen levels. Vaginal cytology • functional (hormonal) – cell appearance is classified (menstrual cycle or pathophysiological gravidity can be monitored) • onkological – cells received from endocervix and stained according to Papanicolau (pap smears signed as PAP I – V, now known as Bethesda system) are studied. Superfitial cells Intermediate cells Parabasal cells Basal cells Vaginální epitel – cytologie Classification of vaginal epithelial cells (cell size, staining of cytoplasm, nucleo-cytoplasmic ratio) Superfitial cells – during proliferative phase (estrogen influence) Intermediate cells – during secretory phase (progesterone influence) + leukocytes in smear Parabasal cells – during childhood or senium (epithelial atrophy) Basal cells – normally not present in smears (indicate a deep damage of the epithelium) Labium minus sebaceous glands Labium minus Human placenta • discoidalis • olliformis • hemochorialis Human placenta • pars fetalis – chorionic plate, chorionic villi (anchoring, free) • pars materna – decidua basalis • intervillous space Placental barrier: • Midgestation: endothelium of capillaries + basal membrane, CT, cytotrofoblast, basal membrane of syncytiotrofoblast, syncytiotrofoblast • 5th month to birth: endothelium of capillaries + basal membrane, basal membrane of syncytiotrofoblast, syncytiotrofoblast Functions • transport (O2, CO2, ions, water, nutrition, hormones, antibodies, metabolites, chemical substances, drugs, infection agens) • endocrine (hCG, somatomamotropin, tyrotropin, kortikotropin; progesteron, estrogens) • metabolic (glycogen, cholesterol, fatty acids) 7. Female reproductive system – II Slides: 47. Uterus – proliferative phase (HE) 48. Uterus – secretory phase (HE) 49. Vagina (Best’s carmine) – glycogen 50. Vagina (HE) 51. Labium minus (HE) 99. Funiculus umbilicalis (HE or Azan) 100. Placenta (HE)