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Female Reproductive Endocrinology Chapter 18. Anatomy Vulva – external genitalia Vagina –Functions: Sperm, menstrual flow passage Receptacle for penis.

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Presentation on theme: "Female Reproductive Endocrinology Chapter 18. Anatomy Vulva – external genitalia Vagina –Functions: Sperm, menstrual flow passage Receptacle for penis."— Presentation transcript:

1 Female Reproductive Endocrinology Chapter 18


3 Anatomy Vulva – external genitalia Vagina –Functions: Sperm, menstrual flow passage Receptacle for penis Birth canal –Rugae –Acidic environment


5 Uterus –Functions: Sperm transport Implantation fert’d ovum Fetal dev’t Labor Menstruation –Cervix secretes mucus

6 Uterus – cont’d –Three histological layers Perimetrium – outside Myometrium – sev muscle layers + connective tissue –Forms bulk of uterine wall Endometrium – closest to uterine cavity –Covered w/ epithelium –Vascular w/ tubular glands –Further divided  3 layers »Innermost shed w/ menstruation »Outermost  new inner layer during cycle

7 Oviducts –Transport Peristalsis Cilia –Isthmus, ampulla, infundibulum –Not static tube Ovaries = gonads –Inner medulla, outer cortex –Gametogenesis, hormonogenesis


9 Ovaries Prepubertal –Anatomy Smooth outer germinal epithelium Connective tissue Cortex w/ ovarian follicles in stroma –Low quantities of sex steroid Feedback inhibition of gonadotropins Puberty  gonadotropins  sex steroids –LH  PKA  StAR  P450scc in partic cells –FSH  E2 secr’n in partic cells

10 Ovarian Cycle Controls, controlled by hormones Coupled to uterine cycle Related to maturation ovarian follicles –Gonadotropin dependent Two phases –Follicular –Luteal

11 Follicular Phase Variable length Maturing follicles secrete –17  -estradiol –Inhibin Absence functional CL –Plasma progesterone low FSH elevated @ beginning, diminishes –High FSH impt to follicle selection, early maturation

12 As follicle dev’s, more E2, inhibin  –Decr’d FSH (neg feedback) –Decr’d LH –Upregulation ant pit GnRH receptors E2 peaks @ midcycle  FSH/LH surge Now new ability some ovarian cells to produce sex steroids (progesterone) Now ovum released from mature follicle


14 Luteal Phase Invariant 14+2 d length CL begins, develops, dies CL secretes progesterone (also E2, inhibin) as matures –Progesterone  postov decr LH, FSH (neg feedback) –Midluteal peak over week –E2 minimally elevated

15 Hormone secretion diminishes as CL declines –If no fertilization –Get sharp decline in plasma progesterone Now less neg feedback due to progesterone –  FSH/LH again secreted –FSH influences new follicle selection, early maturation


17 Gametogenesis Ovarian follicles named by maturation stage Primordial –Primary oocyte –Squamous epithelium; single layer Dev’s  granulosa cells –Growth & remodeling –40  ; oocyte 15-25  –Quiescent


19 Primary follicle –Oocyte enlarges (80-100 m) –Follicle epithelium Simple cuboidal “Granulosa cells” Express FSH receptors –FSH response  organize, stratify granulosa cell layers –Zona pellucida (glycoprotein layer) deposits –Stroma begins to organize as theca

20 Secondary=preantral follicle –Granulosa proliferates, stratifies Signaled by oocyte growth factors –Growth Differentiation Factor 9 (GDF-9) –Bone Morphological Protein 15 (BMP-15) Mitosis and/or pattern of arrangement stim’d –Simple cuboidal  stratified, pseudostratified columnar –Diff layers have diff morphology, function –Granulosa cells produce activin Stim’s FSH receptor synth –Granulosa cells become sensitive to FSH Impt to selection Impt to differentiation Impt to maturation

21 Figure 9. The early differentiation of the granulosa cells during preantral folliculogenesis involves the expression of FSH receptors. Animal studies support the concept that this process involves an activin autocrine/paracrine mechanism. (Erickson GF: Dissociation of Endocrine and Gametogenic Ovarian Function. In Lobo, R. (ed.): Perimenopause. Serono Symposia, Springer-Verlaag, 1997. Reproduced with permission from Springer-Verlag, New York.)

22 Secondary follicle – cont’d –Granulosa cells connected by gap junctions Synchronization Nutrient transfer –Basement membr dev’s –When 6 layers granulosa Definitive theca layer Angiogenesis  blood supply to theca

23 Secondary follicle (cont’d) –Final 2 o follicle 100-200  Fully grown oocyte w/ zp Approx 9 layers granulosa Basal lamina Theca interna w/ capillary net Theca externa

24 Granulosa cells

25 Thecal cells

26 Tertiary=antral follicle –Chamber –Follicular fluid contains hormones Blood-derived From oocyte From granulosa cells –Cavitation signalled by follicle cells –Corona radiata = granulosa cells anchored to zp –Theca fully developed

27 Tertiary follicle – cont’d –Theca interna = steroid producing (androstenedione) Extensive sER, cytoplasmic lipid droplets, tubular mitoch cristae Receptors for LH, insulin Richly vascularized –Theca externa Smooth muscle cells Autonomic neurons

28 Figure 12. Photomicrograph of an early tertiary follicle 0.4 mm in diameter at the cavitation or early antrum stage. zona pellucida (ZP); granulosa cells (GC); basal lamina (BL); theca interna (TI); theca externa (TE); granulosa mitosis (arrowheads). (Bloom W, Fawcett DW In A Textbook of Histology. Philadelphia, WB Saunders Company, Philadelphia 1975. With permission from Arnold.)

29 Preovulatory=Graafian follicle –Now single, dominant follicle –Overall size varies; deter’d by amt follicular fluid –Cumulus oophorus = oocyte + corona radiata Will be expelled @ ovulation –Hyaluronic acid accumulates Break attachment corona radiata and granulosa –LH surge induces completion 1 st meiotic division  2 o oocyte 2 nd meiotic division @ fert’n


31 Ovulation Induced by LH surge Rupture –Follicle wall –Follicle cell layers  Corona radiata w/ oocyte expelled into peritoneal cavity


33 Luteinization Initiated by LH surge CL forms from –Graunulosa lutein –Theca lutein –Assoc’d microvasculature Defined life span –If no fertilization, involution & apoptosis 14 d after form’n

34 Contributes to next developing cohort of follicles –CL degeneration  decr’d E2, inhibin A –  incr’d FSH –  incr’d FSH in follic fluid of Graafian follicle –  dominant follicle selection, maturation

35 Atresia Remaining 99.9% follicles Apoptosis of oocyte, granulosa cells –Ligand signalling pathways  cell death FSH=survival factor –Prevents apoptosis

36 Ovarian Steroidogenesis Maturing follicles and CL Maturing follicles – 2 adjacent impt pop’ns –Granulosa cells –Theca interna cells CL – impt cells der’d from follicle after ov’n –Granulosa lutein –Theca lutein

37 Sex steroids –Prior to ov’n (from maturing follicle): E2 –After ov’n (from CL): progesterone + E2 Book notes progesterone=distinctive female hormone –CL and placenta only Cell pop’ns coordinate in prod’n sex steroids


39 Theca (interna & externa) express P450scc –Cholesterol  pregnenolone –Sensitive to LH  cAMP  PKA  StAR  PBR  P450scc activity in inner mitoch membr –Pregnenolone  androgen pathway Uses P450c17 –Preovulatory LH surge  Ovulation Luteinization theca interna, granulosa Development CL

40 Theca interna express aromatase (androgens  estrogens) –BUT once ovulation occurs, expression ceases –So decr’d secr’n estrogens from CL

41 Granulosa cells lack P450scc, P450c17 –No cholesterol  pregnenolone –No further androgen synth –Rely on theca cell androgens –Insensitive to LH signal for androgen prod’n EXCEPT when advanced follicle dev’d –Just prior to ov’n –Small numbers LH receptors expressed –LH stim’s steroidogenesis in these cells –Impt to luteinization

42 Granulosa cells – cont’d –BUT sensitive to FSH FSH stim’n  –Proliferation granulosa cells –Secretion inhibin B –Expression aromatase through cAMP, PKA act’n Granulosa cells express aromatase –Androgens  estrogens –Most impt source of E2


44 Granulosa lutein cells express P450scc –So can produce pregnenolone BUT granulosa lutein cells lack P450c17 –No androgen synth from pregnenolone Rely on theca lutein cells for androgens –BUT progesterone synth from pregnenolone –Insensitive to LH signal to produce androgens BUT small numbers LH receptors expressed in advanced follicle LH  secr’n progesterone, secr’n inhibin A

45 Granulosa lutein cells express aromatase –Androgens  estrogens –Activated with LH If pregnancy, interrelationships balanced also with placental cells


47 Endometrial (Uterine) Cycle Coupled to ovarian cycle –Gametogenesis –Hormonogenesis Three phases

48 Menstruation – during follicular phase –With demise of CL –Plasma progesterone decr’d –Uterine endometrium shed Leaves basal portion of endometrial glands –2-7 d (4 d avg) –30 mL blood loss avg

49 Proliferative – during follicular phase –E2 dependent regeneration, growth of endometrium –E2 receptor binding @ remaining basal stratum  stromal, epithelial cell growth Secretory – during luteal phase –Progesterone-dependent maturation of endometrium –Requires E2 prep’n endometrium –Now suitable for blastocyst implantation





54 Vaginal Cycle After puberty In response to estrogens –Changes w/ menstrual cycle Early follicular phase –Epithelium rounded basal cells Late follicular phase – maximum growth –Basal cells covered w/ flattened cells –Outermost cells keratinized End luteal –Epith invaded w/ leukocytes, dead cells degen’d

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