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Physiology of Reproduction(I)
Teng Yincheng M.D., Ph.D., Professor
Department Of Obstetrics & Gynecology
Renji Hospital Affiliated to SJTU School of Medicine
Two Major Phases of Female Reproductive Function
• Preparation of the body for conception
• Pregnancy
1.Women’s Physiological Stages
• Neonatal period: birth---4 weeks
• Childhood: 4 weeks----12 years
• Puberty: 12 years---18 years
• Sexual maturation: 18 year---50 year
• Perimenopause: decline of ovarian function (40 years)----1 year postmenopause
• Postmenopause:
2.Menstruation• Menstruation cyclic endometrium sheds and bleeds due to cyclic ovulation
and ovarian hormones changes• Mense1. Endometrium is sloughed (progesterone withdrawal)2. Nonclotting menstrual blood mainly comes from artery
(75%)3. Interval: 24-35 days (28 days). duration: 2-6 days. the first
day of menstrual bleeding is consideredy by day 14. Shedding: 30-50 ml
Female Reproductive System
Ovary
UterusFallopian tube
fertilization site
3.Female Hormone System(H-P-O axis)
1)Hypothalamus:Gonadotropin-releasing hormone (GnRH); also called LHRH
2)Anterior pituitary:Luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
3) Ovary: Estrogens and progesterone
The hormones secrete at different rates during different timesof the month
Ovaries
Interaction of thefemale hormonesystem and theirfunctions
• GnRH: anterior pituitary LHand FSH
• LH & FSH: ovary; developmentof ovarian follicles; estrogen andprogesterone production
• Progesterone: endometrium &breasts
• Estrogen: ovary, uterus, breasts
Female sexual cycle (menstrual cycle): • Average 28 days/cycle (20-45 days) • A single ovum released from ovaries per month• Uterine endometrium: preparation for implantation
of fertilized ovum
FSH & LH are essential for the function of the ovaries• <8 years old: no FSH & LH• >8 years old: FSH & LH culminate monthly cycle• Menarche & Puberty - onset of the adult sexual life
Function of Anterior Pituitary Gonadotropic Hormones in controlling the Ovarian Cycle
4.The Ovarian Cycle and Hormones
1)Oogenesis7,000,000
20-24 weeks gestation
1,500,000
Birth
400,000
Puberty
Mit
osis
Attrition
300,000-400,000 ova400-500 ovulations in 13-46 years of age
2)Ovarian Follicular Growth(Each ovum is enclosed within a follicle)
Primordial follicle: 50μmovum + one layer of granulosa cells
Primary(preantral )follicle:200μmovum + more layers of granulosa cellsZona pellucid FSH-R aromatase
antral follicle: 500μmovum + granulosa + theca cells + follicular fluid (Estrogens)LH-R cumulus oophorus estrogens
Mature (Graafian) follicle: 15-20mmone follicle outgrows
Follicular phase
Granulosa cells
Zona pellucida
Corona radiata
Antrum
Interstitial tissue
Primodial follicle
Ova
Cumulus oophorus
Primordial Follicle and Mature Follicle
Thecainterna
Theca externa
AntrumTheca
GranulosaOvum
One follicle outgrows Estrogens
Other follicles involute
FSH & LH Receptors
(+)
Pituitary FSH & LH
(-)
One follicle maturation Estrogens
Maturation of only one follicle each month, atresia of the remainder
(+)Hypothalamus GnRH
Ovaries~20-25 follicles develop each month
Controlling factor: vascularity?
Estrogen Synthesis
Androstenedione
17-Estradiol
O=
O
TestosteroneO=
OH
OH
HO-
Cholesterol
Estrone
O
HO-
17-Hydroxysteroid Dehydrogenase
LH
aromatase aromataseFSH FSH
Thecal Cells
Granulosa Cells
17 -Hydroxysteroid Dehydrogenase
Estriol
OH
HO-
Peripheral
OH
Cholesterol Cholesterol
Pregnenolone
Progesterone
Pregnenolone
Progesterone
17-Hydroxysteroids
Testosterone Androstenedione
ATP cAMP
Protein Kinase A
Testosterone Androstenedione
Nucleus
Estrone
Aromatase
cAMP
ATP
Protein Kinase A
Thecal Cells
Granulosa Cells
FSH
LH
LDL
3)Preantral Thecal and Granulosa Cells & Estrogen Synthesis
Estradiol
Estrone
Circulation
Aromatase
desmolase desmolase
Lyase
AntrumEstradiol
4)Feedback Control of Gonadotropin Secretion
GnRH
At level of hypothalamus/pituitary:• Circulating estrogens inhibit LH & FSH secretion• Circulating progesterone (low) potentiatesestrogen feedback effects• Circulating inhibin inhibits FSH secretion
At level of ovary:• Receptors for LH (thecal cells) and FSH (granulosa cells) increase in maturing follicle• Cellular hypertrophy• Proliferation of granulosa/theca increases circulating estrogens that participate in negative feedback
-
Inhibin
Cholesterol Cholesterol
ProgesteronePregnenolone
Progesterone
17-Hydroxysteroids
Testosterone Androstenedione
ATP cAMP
Protein Kinase A
Testosterone Androstenedione
Nucleus
Aromatase
cAMP
ATP
Protein Kinase A
Thecal Cells
Granulosa Cells
FSH
LH
LDL
Control of Mature Graafian Follicle Estrogen Synthesis
Estradiol Estrone Antrum
Circulation
Aromatase
desmolase desmolase
cAMP
ATPLyase LH receptors increase
in Antral Stage Only -estrogen induced
LH
FSHPregnenolone
EstradiolEstrone
Feedback Control of Gonadotropin Secretion just prior to Ovulation
GnRH
At level of granulosa and theca:• Theca: increased androgen precursor production• Granulosa: LH/FSH receptors induced; aromatase induced; increased estrogensynthesis• Proliferating cells elevate estrogen to critical concentrations
At level of circulation & pituitary:• Increase in circulating estrogen and progesterone• Positive feedback by estrogen on pituitary FSH & LH secretion FSH/LH “spike”• LH “spike” induces ovulation
Estrogen Feedback on Hypothalamus and Anterior Pituitary
What explains the differential effect of estradiol on pituitary release of LH/FSH?
Mammalian Ovarectomy:
FSH, LH within 1-2
days
Remove ovaries
Pituitary surge:
especially of LH
Give exogenous estrogen
Estrogen Pituitary(-)
•Estrogen feedback is time and dose-dependent •Critical plasma level of >200 pg/ml sustained for 2 days is required for positive feedback•Mechanisms differ w/mammalian species
Estrogen Feedback on Hypothalamus and Anterior Pituitary
Give higher dose of estrogen
Estrogen Pituitary(+)
LH/F
SH
Preovulatory Surge of LH
• LH is necessary for final follicular growth and ovulation
• Two days before ovulation, LH increases 6-10 fold. FSH secretion increases 2-3 fold at the same time
• LH surge: caused by positive feedback induced by peak estrogen secretion
• LH & FSH act synergistically to cause rapid swelling of the follicle
The Ovary and Process of Ovulation
Primordial follicle
Ovulation
Ovarian vessels
Corpus hemorrhagicumCorpus luteum
Corpus albicans
- Outer wall of the follicle swells rapidly- Follicular fluid oozes out- Wall of the follicle ruptures- Viscous fluid carries ovum and
granulosa cells (corona radiata) into abdominal cavity
Ovulation in a woman who has a normal 28-day cycle occurs 14 days after the onset of menstruation
Developingfollicles
Maturefollicle
Luteal Phase of the Ovarian Cycle
Corpus albicans
Mature corpus luteum
Ovulation
Early corpusluteum
• Luteinization: conversion of thecal & granulosa cells to lutein cells corpus luteum
• Corpus luteum: Secretion of estrogen,progesterone, inhibin
• LH: - stimulates lutein cell formation & growth - enhance corpus luteum secretion- extends corpus luteum lifetime
GnRH
Anterior Pituitary
FSH & LH
Ovary
EstrogenProgesteroneInhibin
(-)
(+)
(+)
HypothalamusTermination of the ovarian cycle and onset of the next cycle
(-)- Estrogens feedback at the hypothalamus and pituitary to inhibit LH and FSH secretion
- Progesterone potentiates estrogen feedback effects
- Inhibin mainly inhibits FSH secretion
Feedback loops
5.Monthly Endometrial Cycle & Menstruation
Estrogen phase(before ovulation)Secrete thin mucus
Progestational phase (after ovulation) Secrete uterine milk
Vessels constrictEndometrium necrosis
40ml blood + 35ml fluid Fibrinolysin → nonclotting
Leukocytes → anti-infection
Ovulation
FSH
LH
Estradiol
Progesterone
Hypothalamus
Anterior Pituitary
Ovarian Events
UterineEndometrium
Summary of the Monthly Cycle
• Every 28 days, gonadotropic hormones FSH and LH from anterior pituitary cause new follicles to grow in ovaries. During early growth of the follicles, estrogen is secreted, causing the proliferative changes of uterine endometrium.
• One of the follicles is ovulated at the 14th day of cycle. After ovulation, secretory cells of follicle develop into corpus luteum which secretes large quantities of estrogen and progesterone, causing the secretory changes in uterine endometrium.
• In another two weeks, corpus luteum degenerates, causing a decrease in progesterone and estrogen. The sudden reduction of ovarian hormones causes menstruation. Then a new cycle follows.
• BBT increases after ovulation.
GnRH
OvarianHormones
GonadotropicHormones
Days of Cycle
Basal BodyTemperature
6.Functions of Ovarian Hormones: Estradiol & Progesterone
Two classes of ovarian sex hormones: • Estrogens and progestins • The most important of the estrogens is estradiol • The most important progestin is progesteroneEstrogens:
Promote proliferation and growth of sex related cells; cause secondary sexual characteristics
Progestins: Important for preparation of the uterus for pregnancy and the breast for lactation
1)Effects of Estrogens on Primary and Secondary Female Sexual Characteristics
Principal Function: cellular proliferation; growth of the tissues of sexual organs; growth of other tissues related to reproduction
Estrogen
Uterus, externalFemale sex organs
Breasts
Fat/proteindeposition
Skeleton
Electrolytebalance
Skin
2)Estrogen effects on the Uterus & External Female Sex Organs
• Tissue enlargement: fallopian tubes, uterus, vagina, and all external genitalia
• Vaginal epithelium: Cuboidal into stratified type; increase resistance to trauma and infection
• Facilitate transport of fertilized ovum toward uterus: Increase fallopian cilia number tubelocking
• Proliferate endometrial glands in fallopian tubes and uterus: Nourish implanting ovum
Estrogen effects on:Breast• development of ductile system, stroma tissues & fat deposition mature female breastFat/Protein deposition• fat deposition in subcutaneous & breast tissues; broadening of thighs/ buttocks• protein deposition in sexual organs, bones; slight increase in total body proteinSkeleton• Increase osteoblastic activity, growth plate unit• Post menopause: decrease osteoblast activity, bone matrix, Ca/P depositsElectrolyte Balance• Increase sodium & water retention – effect is greater during pregnancySkin• Development of thick, soft & smooth skin texture• Vascularization increase bleeding
2)Functions of Progesterone
1. UterusPromotes secretory changes in uterine endometriumDecreases uterus contraction
2. Fallopian tubes Promotes secretory changes in mucosal lining
3. Breasts Promotes development of lobules, alveoli of breasts:alveolar cells proliferate, enlarge, and become secretory
Estrogen Secretion Throughout theFemale Sexual Life
Other hormones
Thyronine and triodothyronine
Congenital adrenal hyperplasia ACTH
21- 羟化酶缺陷—皮质激素合成不足 ---ACTH
Progesterone and 17- 羟孕酮 -------testosterone
女性假两性畸形Insulin –dependent diabetes millitus
THANKS FOR YOUR ATTENTION
Teng YinchengTeng Yincheng
M.D., Ph.D., ProfessorM.D., Ph.D., Professor
Dep. of Obstet. & Gynecol.Dep. of Obstet. & Gynecol.
Renji Hospital Affiliated to SJTU School of MedicineRenji Hospital Affiliated to SJTU School of Medicine