female reproductive physiology

Obstetrics & Gynecology Hospital

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Female Reproductive Physiology


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What you need to know

• One axis: H-P-O axis

• One figure : menstrual cycle physiology


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Pituitary

Hypothalamus

Ovary

Axis


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Ovarian cycle

Uterine cycle

LH P

E2

FSH

Hormone variation

Menstrual Cycle Physiology


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Anatomy &

Female Development


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Female genital anatomy


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Female development

Fetal period

Neonatal period

childhood

Adolescencepuberty

Sexual maturity

Menopausal transition

period

Postmenopausal period


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Female development

• Fetal period– Ovary develops during 8-10 week’s of pregnancy

• Neonatal period– Within 4 weeks after birth– Temporary lactation or vaginal bleeding may

occur

• Childhood– 4 weeks after birth → 10 years old– Low hypothalamus - pituitary gland – ovary axis

function– Uterine body : cervix 1:2


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Female development• Adolescence / puberty

– 10-19 years old– Onset of hypothalamus - pituitary gland –

ovary axis function– Uterine body : cervix 2:1– Development of second sexual

characteristics

• Thelarche• Adrenarche• Growth spurt• Menarche


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Female development• Sexual maturity

– From 18 years old and lasts for about 30 years

– Mature hypothalamus - pituitary gland – ovary axis function

– Reproductive age

• Menopausal transition period– Lasts 1-10 years till menopause– Declined ovarian function– Vasomotor symptoms

• Postmenopausal period– Ceased ovarian function


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Hypothalamus—Pituitary Gland —

Ovary

Axis


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Hypothalamus

Pituitary

Ovaries

Thyroid

Adrenal

glands


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Neuro-endocrine regulation


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Anatomy


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Major secretory products of the hypothalamus ----pituitary-releasing factors

• Gonadotropin-releasing hormone (GnRH) Luteinizing hormone (LH) Follicle-stimulating hormone (FSH)

• Corticotropin-releasing hormone (CRH) Adrenocorticotrophic hormone (ACTH)

• Growth hormone–releasing hormone (GHRH) Growth hormone (GH)

• Thyrotropin-releasing hormone (TRH) Thyroid-stimulating hormone (TSH)


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Gonadotropin-releasing Hormone (GnRH)

• A decapeptide produced by hypothalamus• Simultaneously regulates the secretion

FSH and LH• Must be secreted in a pulsatile fashion to

be effective• Continual exposure to GnRH results in

downregulation of GnRH receptors in gonadotroph cells


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Gonadotropin-releasing Hormone

• Extremely short half-life (only 2–4 minutes)

• The pulsatile secretion varies in both frequency and amplitude throughout the menstrual cycle

• GnRH agonist & antagonist----medical castration


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portal vessels ----bidirectional feedback control between the hypothalamus and pituitary.

Anterior pituitary (adenohypophysis) Posterior neural pituitary

(neurohypophysis)

Pituitary

Intermediate part


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Major secretory products of the anterior pituitary

• Gonadotropins ： FSH ， LH• Growth factor (GH)• Prolactin (PRL)• ACTH • TSH


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HCG

Gonadotropins

• FSH Folicullar stimulating hormone• LH Luteinizing hormone• Responsible for ovarian follicular stimulation• FSH ， LH ， TSH and HCG share the same a -

subunit


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Prolactin• Responsible for the synthesis of milk by the breast• Stimulated by: breast manipulation, drugs, stress,

exercise, and certain foods• Hyperprolactinemia : amenorrhea galactorrhea

Thyroid-stimulating Hormone• Stimulates release of T3 and T4 from the thyroid

gland• Abnormalities of thyroid secretion (both hyper- and

hypothyroidism) are frequently associated with ovulatory dysfunction


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Adrenocorticotrophic Hormone • Secreted in response to CRH• Stimulates the release of adrenal

glucocorticoids.• Diurnal variation ： early morning peak and a

late evening nadir• Negatively regulated by feedback from cortisol.

Growth Hormone• Greatest absolute amount of the anterior

pituitary hormone• Secreted in response to GHRH, thyroid hormone

and glucocorticoids• Secreted in a pulsatile fashion with peak

release occurring during sleep.


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Major secretory products of the posterior neural pituitary

• Oxytocin• Arginine-vasopressin


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Oxytocin

• A nine–amino acid peptide • Stimulates of uterine muscular contraction;

breast lactiferous duct myoepithelial contractions

• Stimulated by suckling


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Arginine-vasopressin (antidiuretic hormone, or ADH, AVP)

• Major function : increase blood pressure – arteriolar vasoconstriction– renal free-water conservation– decrease in blood osmolality


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Ovarian cycle

Uterine cycle

LH P

E2

FSH Hormone variation



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Menstrual cycle

Normal menstrual cycle– orderly cyclic hormone production– parallel proliferation of the uterine lining– prepare for implantation of the embryo

Disorders of the menstrual cycle / menstrual physiology – infertility– recurrent miscarriage– Irregular bleeding – Malignancy


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Menstrual cycle

Follicular phase Luteal phase

Proliferative phase Secretory phase

Ovarian cycle

Uterine cycle


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Menstrual cycle• Follicular phase

– development of a single dominant follicle, which should be mature at midcycle and prepared for ovulation.

– average length : 10 to 14 days– variable in length– Proliferative phase

• Luteal phase– the time from ovulation to the onset of menses– an average length of 14 days– Secretory phase

• Normal menstrual cycle– 21 to 35 days, with 2 to 6 days of flow– an average blood loss of 20 to 60 mL


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Hormone variation


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Hormone variation• Beginning of menstrual cycle

– Low gonadal steroids – FSH begins to rise with a cohort of growing follicles

recruited– Follicles secrets estrogen↑---- stimulates uterine

endometrial proliferation

• Midpoint of the follicular phase– Rising estrogen and inhibin-B inhibits pituitary FSH

secretion

• Late in the follicular phase– High estrogen stimulates LH secretion (biphasic

response).

• Before ovulation– FSH-induced LH receptors are present on granulosa

cells– LH stimulates progesterone secretion– Estrogenic stimulation triggers pituitary LH surge,

causes ovulation 24 to 36 hours later

LH

E2

FSH

P


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Hormone Variation• Ovulation

– Heralds the transition to the luteal–secretory phase

• Early luteal phase – Estrogen level decreases

• Midluteal phase– Estrogen, inhibin-A increase (secreted by the

corpus luteum)

• Progesterone levels rise precipitously after ovulation : presumptive sign of ovulation

• Progesterone, estrogen, and inhibin-A – act centrally to suppress gonadotropin secretion

and new follicular growth. – remain elevated through the lifespan of the

corpus luteum and then wane with its demise

LH

E2

FSH

P


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Uterine cycle


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Uterine cycle

Proliferative phase Secretory phase


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Cyclic Changes of the Endometrium

Stratum compactum

stratum spongiosum

decidua basalis

decidua functionalis

myometriumAsherman's Syndrome

Loss of function


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• Proliferative Phase– progressive mitotic growth of the decidua

functionalis in response to rising circulating levels of estrogen

– endometrial glands: straight, narrow, short ￫￫ longer, tortuous structures

– mitotic cells lining proliferating glands: low columnar pattern ￫￫ pseudostratified pattern

– stroma: dense compact layer– vascular structures: infrequently seen


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• Secretory Phase– Ovulation occurs 14 days before mense– Endometrium shift to secretory phase within 48 to

72 hours following ovulation in response to progesterone secretion

– Stroma: progressive increase in edema at approximately the seventh postovulatory day

– Spiral arteries progressively lengthen and coil– Pseudodecidual d24


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• Secretory Phase– Presence of eosinophilic protein-rich secretory

products in the glandular lumen– Acid–Schiff positive–staining, glycogen-containing

vacuoles.– Leukocytic infiltration heralds the collapse of the

endometrial stroma and the onset of the menstrual flow (2 days before mense)



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• Menses– In the absence of implantation– Shedding of decidua functionalis is termed

menses. – The destruction of the corpus luteum and its

production of estrogen and progesterone is the presumed cause of the shedding.

– Prostaglandins release: vasospasm ; endometrial ischemia ； myometrial contractions



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Ovarian cycle


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Number of oocytes during life time

500

6- 7 mi l l i on

1- 2 mi l l i on

300, 0000

10000002000000300000040000005000000600000070000008000000

20 weeks ofgestat i on

bi rth puberty rel eased ovum

No o

ocyt

es

oogonia atresia.


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Development of oocyte

oogoniaPrimary oocyte

Enter Meiosis Ⅰ

Secondary oocyte

Finish Meiosis Ⅰ

ovulationbirth• Meiotic arrest

16-20 weeks of gestation Stops at prophase I of meiosis I

• Meiotic resumptionMeiosis resumes until the time of ovulation

Enter Meiosis Ⅱ


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Oogonia

Primary oocyte

(Primordial follicle)Birth

Development of oocyte

Ovulation


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Theca cells: LH-R(+), produce sex steroids

Granulosa cells: FSH-R,E-R,A-R,LH-R,PRL-R (+)

Follicle


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Follicle development

Primordial follicles

decades 9 months

Preantral follicles

Antral follicles

preovulatoryfollicle

Ovulation

3 months Follicular phase

recruitmentrecruitment selectionselection Dominant follicle

Primary oocyte


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Primordial follicle

Preantral

follicle FSH-R

E-R

A-R

Antral follicle

Preovulatory follicle

(18-23mm)

FSH-R

E-R

A-R

LH-R

PRL-R

FSH stimulation

cumulus oophorus.

LH-R

Recruitment

Selection

Dominant follicle


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Two-cell Two-gonadotropin Theory

• there is a subdivision and compartmentalization of steroid hormone synthesis activity in the developing follicle

granulosa cells

theca cells

aromatase

androgen

estrogen

cholesterolLH

FSH


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Preovulatory Follicle

• Fluid-filled antrum

• The oocyte remains connected to the follicle by the cumulus oophorus.

• Rising estrogen ￫￫ negative feedback on FSH secretion

• Estrogen has biphasic regulation on LH– Lower level ￫￫ inhibit LH secretion

– Sustained High level((200 pg/mL) for more than 48 hours) ￫￫ enhances LH release


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Ovulation

• LH surge ￫￫ initiation of ovulation• Occur in the single mature, or Graafian,

follicle 10 to 12 hours after the LH peak or 34 to 36 hours after the initial rise in midcycle LH

• Dramatic increase in local concentrations of prostaglandins and proteolytic enzymes in the follicular wall

• Slow extrusion of the oocyte through perforation of follicular wall


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Luteal Phase

• The remaining follicular shell after ovulation is transformed into the corpus luteum

• Membranous granulosa cells begin to take up lipids

• Produce progesterone to support endometrium

• Produce estrogen and inhibin A• Inhibit FSH, LH• Inhibit follicular development and

recruitment


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Luteal phase• Continued corpus luteum function

depends on continued LH production.• No pregnancy: corpus luteum regress

after 12 to 16 days and form the scarlike corpora albicans

• Pregnancy : placental hCG stimulates the corpus luteum to secrete progesterone


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KEY POINTS


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Hypothalamus

Pituitary

Ovaries

GnRH

LH FSH

Endometriium

E2 P


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Ovarian cycle

Uterine cycle

LH

P E2

FSH


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• GnRH is produced in the arcuate nucleus of the hypothalamus and secreted in a pulsatile fashion into the portal circulation, where it travels to the anterior pituitary.

• Ovarian follicular development moves from a period of gonadotropin independence to a phase of FSH dependence.

• As the corpus luteum of the previous cycle fades, luteal production of progesterone and inhibin A decreases, allowing FSH levels to rise.


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• In response to FSH stimulus, the follicles grow and differentiate and secrete increasing amounts of estrogen and inhibin-B.

• Estrogen stimulates growth and differentiation of the functional layer of the endometrium, which prepares for implantation. Estrogens work with FSH in stimulating follicular development.

• The two-cell two-gonadotropin theory dictates that with LH stimulation, the ovarian theca cells will produce androgens that are converted by the granulosa cells into estrogens under the stimulus of FSH.


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• Rising estrogen and inhibin levels negatively feed back on the pituitary gland and hypothalamus and decrease the secretion of FSH.

• The one follicle destined to ovulate each cycle is called the dominant follicle. It has relatively more FSH receptors and produces a larger concentration of estrogens than the follicles that will undergo atresia. It is able to continue to grow despite falling FSH levels.


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• Sustained high estrogen levels cause a surge in pituitary LH secretion that triggers ovulation, progesterone production, and the shift to the secretory, or luteal, phase.

• Luteal function is dependent on the presence of LH. However, the corpus luteum secretes estrogen, progesterone, and inhibin-A, which serve to maintain gonadotropin suppression. Without continued LH secretion, the corpus luteum will regress after 12 to 16 days. The resulting loss of progesterone secretion results in menstruation.

• If pregnancy occurs, the embryo secretes hCG, which mimics the action of LH by sustaining the corpus luteum. The corpus luteum continues to secrete progesterone and supports the secretory endometrium, allowing the pregnancy to continue to develop.


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Thank you !

female reproductive physiology

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