439EnFemRepro16.pptx

7/27/2019 439EnFemRepro16.pptx

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FEMALE REPRODUCTIVE SYSTEM


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TO REVIEW THE COMPONENTS OF THEFEMALE REPRODUCTIVE SYSTEM

TO UNDERSTAND THE HORMONALREGULATION OF OOGENESIS, OVULATION,AND THE UTERINE CYCLE

TO CHARACTERIZE THE GENERAL

ORGANIZATION OF THE OVARIES



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Hormones of the Female

Reproductive Cycle

Control the reproductive cycle

Coordinate the ovarian and uterine cycles


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Hormones of the Female

Reproductive Cycle

Key hormones include:

FSH

Stimulates follicular development

LH Maintains structure and secretory function of corpus

luteum

Estrogens

Have multiple functions

Progesterones

Stimulate endometrial growth and secretion


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OVARIES OVIDUCT (UTERINE TUBES) UTERUS VAGINA



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Female Reproductive Organs

Ovary: female gonad

Uterine Tubes (fallopian tube, oviduct)

- three parts: infundibulum, ampulla, isthmus


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The Female Reproductive System in Midsagital View


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The Ovaries and Their Relationships to the

Uterine Tube and Uterus


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The Uterine Tubes


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The Uterus

Muscular organ

Mechanical protection

Nutritional support

Waste removal for the developing embryo and fetus

Supported by the broad ligament and 3 pairs of

suspensory ligaments


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Uterine Wall Consists of 3

Layers: Myometriumouter muscular layer

Endometriuma thin, inner, glandular mucosa

Perimetriuman incomplete serosa continuous

with the peritoneum

The site of implantation of developing embryo

And 3 parts: fundus, body, and cervix


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Female Accessory Sex Organs: Uterus

Uterine endometrium has two layers:

- basal layer

- functional layer: built up and shed each cycle


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Figure 28.18a, b

The Uterus


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Figure 28.18c

The Uterus


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Figure 28.19a

The Uterine Wall


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Figure 28.19b

The Uterine Wall


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Figure 28.20

The Uterine CycleTo be discussed below


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Functions of the Ovary

Production of a mature oocyte, capable of

fertilization and embryonic development.

Production of ovarian steroids (estradiol,progesterone).

Production of gonadal peptides (inhibin, activin).


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Structural Organization of the Ovary

The main functional unit of the ovary is the

follicle.

Follicles are composed of the oocyte,granulosa cells, and theca cells.


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Stages of Follicular Growth

Follicles are present in a number ofdifferent stages of growth:

- primordial follicles (resting)

- primary, secondary, and antral follicles- preovulatory (Graafian) follicles


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The Corpus Luteum

After the preovulatory follicle ovulates

(releases its egg), it forms the corpus

luteum.


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OVIDUCT (UTERINE TUBES) UTERUS

INFUNDIBULUM, AMPULLA, ISTHMUS, UTERINE

FUNDUS, BODY (CORPUS), CERVIX


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Oogenesis and Oocyte Maturation

Recall that germ cells must go through meiosis inorder to produce unique haploid cells.

From one spermatogonia, end up with fourspermatozoa.

Oocytes must also go through meiosis, but they doit during the course of follicular development.

Primordial follicles contain primary oocytes thatare arrested in prophase I, prior to the first meiotic

division (diploid).

How do they go through the rest of meiosis?


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Oocyte Maturation

Oocytes remain in prophase I until the

preovulatory surge of LH, which initiatescompletion of the first meiotic division.

The primary oocyte does not split into two cells,

but instead gives off a very small first polar body,

containing half of the chromosomes.

zona pellucida

LH surge

first polar body


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Oocyte Maturation

Thus, the ovulated egg is actually not completely

mature (hasnt completed meiosis II).

Maturation goes to completion only if the oocyte is

fertilized.

Fertilization causes completion of meiosis II, and

expulsion of a second polar body.

Meiosis of the oocyte results in only one gamete.

first polar body first polar body

second polar body

fertilization


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FEMALE REPRODUCTIVE SYSTEMThe Ovarian Cycle

OVARY

- thin connective tissue capsule

underlying germinal epithelium

TUNICA ALBUGINEA

GERMINAL EPITHELIUM

CORTEX

- surrounds the medulla and

contains maturing follicles

MEDULLA

- central connective tissue

containing vascular supply and

nervous innervation


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FEMALE REPRODUCTIVE SYSTEMThe Ovarian Cycle

OVARY3 to 5 million OOGONIA differentiate into

PRIMARY OOCYTES during early development

OOCYTES becomes surrounded by squamous

(follicular) cells to become PRIMORDIAL FOLLICLES

most PRIMORDIAL FOLLICLES undergoatresia leaving 400,000 at birth

oocytes at birth arrested at

Meiosis I (prophase)


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OVARYTHREE STAGES OF OVARIAN FOLLICLES CAN

BE IDENTIFIED FOLLOWING PUBERTY:

(each follicle contains one oocyte)

(1) PRIMORDIAL FOLLICLES

- very prevalent; located in the

periphery of the cortex

- a single layer of squamous follicular

cells surround the oocyte

(2) GROWING FOLLICLES

- three recognizable stages:

(a) early primary follicle

(b) late primary follicle

(c) secondary (antral) follicle

(3) MATURE (GRAAFIAN) FOLLICLES

- follicle reaches maximum size

OO

GENESIS


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OVARIAN FOLLICLES(1) PRIMORDIAL FOLLICLES

(2) GROWING FOLLICLES

(a) early primary follicle

- follicular cells still unilaminarbut now are cuboidal in appearance

- oocyte begins to enlarge

(b) late primary follicle

- multilaminarfollicular layer; cells now termed granulosa cells

- zona pellucida appears; gel-like substance rich in GAGs

- surrounding stromal cells differentiate into

theca interna and theca externa

(b) secondary (antral) follicle

- cavities appear between granulosa cells forming an antrum

- follicle continues to grow

- formation ofcumulus oophorus and corona radiata

(3) MATURE (GRAAFIAN) FOLLICLES


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OVARIAN FOLLICLES

late primary follicle


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OVARIAN FOLLICLES

GRANULOSA (FOLLICULAR) CELLS

ZONA PELLUCIDA

OOCYTE


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OVARY

GERMINALEPITHEL

IUM

T

UNICAALBUGINEA


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OVARYOVARY H&E

PRIMORDIAL

FOLLICLES

EARLY 1


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OVARY OVARY H&E

CORPUS

ALBICANS

EARLY PRIMARY

FOLLICLES

OVARY

PRIMORDIAL

FOLLICLE

FEMA E REPRODUCTIVE SYSTEM


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OVARY

LATE PRIMARY FOLLICLE

multilaminar



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OVARY

MATURE (GRAAFIAN) FOLLICLE

cumulus oophorus

corona radiata

theca interna and externa

zona pellucida

theca interna cells begin to

produce androgens that are

converted to estrogens



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HORMONAL REGULATION OFOOGENSIS AND OVULATION

HYPOTHALAMUS release of GnRF which

stimulates release of LH and FSH from the

adenohypophysis (ANTERIOR PITUITARY)


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Effects of GnRH on Gonadotropins

GnRH is released in a pulsatile manner,

stimulating the synthesis and release of LH and

FSH.

GnRH acts through its receptor on the pituitary

gonadotroph cells, stimulating production of

phospholipase C.

Recall that IP3 pathway causes gonadotropinrelease, while the DAG/PKC pathway causes

gonadotropin synthesis.

A ti f FSH G l C ll


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Actions of FSH on Granulosa Cells

FSH

Gs

AC

ATP

cAMP

PKA

CREB CRE

Steroidogenic

enzymes

LH Receptor

Inhibin Subunits

Plasminogen

Gene Expression


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LH

androgens

estradiol

Theca cells

Granulosa cells

aromatase

FSH

Ovarian Estradiol Production


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Regulation of Progesterone Production

Progesterone is produced from theca cells, mature

granulosa cells, and from the corpus luteum.

In this case, gonadotropins induce expression of- steroidogenic acute regulatory protein

- P450 side chain cleavage


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Actions of Estradiol


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Estradiol also has important actions in a number of

other tissues:- causes proliferation of uterine endometrium

- increases contractility of uterine myometrium

- stimulates development of mammary glands

- stimulates follicle growth (granulosa cellproliferation)

- effects on bone metabolism, hepatic lipoprotein

production, genitourinary tract, mood, and cognition Effects are mediated through the intracellularestrogen receptors (alpha and beta), and possiblemembrane effects.

Actions of Estradiol


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Actions of Progesterone

Progesterone exerts positive and negativefeedback effects on gonadotropin synthesis andrelease.

Progesterone also acts on many tissues:

- stimulates secretory activity of the uterineendometrium

- inhibits contractility of the uterine myometrium

- stimulates mammary growth

The actions of progesterone are mediated throughan intracellular P receptor, which acts as atranscription factor.


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Regulation of Follicle Growth

Primordial follicles can rest for many decadesbefore being recruited for growth by an unknownmechanism.

The recruitment of primordial follicles andsubsequent growth to the small antral follicle stagecan occur without gonadotropin stimulation(gonadotropin-independent).

Small antral follicles (and larger) must bestimulated by FSH and LH in order to continuegrowth to the preovulatory stage (gonadotropindependent).


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Follicular Ovulation

As the preovulatory follicle grows, it producesincreasing amounts of estradiol.

When the preovulatory follicle is mature, plasmaestradiol levels are very high.

High estradiol levels exert positive feedback onthe hypothalamus and pituitary, resulting in LHand FSH surges.

These preovulatory gonadotropin surges causeovulation of the preovulatory follicle (follicularrupture and release of the egg for fertilization).


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Mechanism of Gonadotropin-induced

Ovulation

The preovulatory LH and FSH surges induceexpression of enzymes in the preovulatory folliclewhich break down the follicle wall.

Tissue-type plasminogen activator: results inbreakdown of fibrin.

Metalloproteinases: result in breakdown ofcollagen.

Result: follicle wall is ruptured, resulting inrelease of the oocyte into the peritoneal cavity.

F ti f th C L t


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Formation of the Corpus Luteum

After the follicle ovulates, the remaining granulosa

cells and theca cells luteinize.

Luteinization: accumulation of cholesterol and

lipid, cells swell. Luteinized cells switch the ovary from

predominant production of estradiol to production

of progesterone and estradiol.

This prepares the uterine endometrium for

pregnancy.



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FEMALE REPRODUCTIVE SYSTEMThe Menstrual Cycle HORMONAL REGULATION OF OOGENSIS AND OVULATION

FOLLICULAR PHASE LUTEAL PHASEOVULATION

10-20 primordial follicles begin to develop

in response to FSH and LH levels

FSH and LH stimulate theca and granulosa

production of estrogen and progesterone

surge of LH induces ovulation

theca and granulosa cells transform into the corpus

luteum and secrete large amounts of progesterone

if fertilization does not occur, corpus luteum

degenerates ... if fertilization does occur, HCG

released from the embryo maintains corpus luteum


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Th M t l C l Th Ut


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Proliferative stage: increasing estradiol levels

stimulate proliferation of the functional layer ofthe uterine endometrium.- Results in increased thickness of theendometrium.

- Increased growth of uterine glands (secretemucus) and uterine arteries.

Secretory stage: progesterone acts on theendometrium.

- uterine glands become coiled and secrete moremucus

- uterine arteries become coiled (spiral arteries)

The Menstrual Cycle: The Uterus


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The Menstrual Cycle: The Uterus

If pregnancy doesnt occur, P and E2 levels

decrease at the end of the secretory stage.

- vasospasm of arteries causes necrosis of tissue- loss of functional layer with bleeding of uterine

arteries (menstruation)


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CORPUS LUTEUM(1) GRANULOSA LUTEIN CELLS

(2) THECA LUTEIN CELLS

CORPUS LUTEUM H&E

(1)

(2)



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OVIDUCT

SITE OF FERTILIZATION

TRANSMITS OVA FROM

OVARY TO UTERUS

MUCOSA

EPITHELIUM AND LAMINA PROPRIA

MUSCULARIS

INNER CIRCULAR; OUTER LONGITUDINAL

INCREASES AS APPROACH UTERUS

SEROSA

MEIOSIS II IN PROGRESS AND ULTIMATELY

ARRESTS UNLESS FERTILIZED



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OVIDUCTSIMPLE COLUMNAR EPITHELIUM

TWO CELL TYPES:

(1) CILIATED

(2) PEG CELLS (NONCILIATED)


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HORMONAL REGULATION OF UTERINE CYCLE(1) PROLIFERATIVE PHASE concurrent with follicular maturation and influenced by estrogens

(2) SECRETORY PHASE concurrent with luteal phase and influenced by progesterone

(3) MENSTRUAL PHASE commences as hormone production by corpus luteum declines


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O UC S S

UTERUSPROLIFERATIVE PHASE

tubular uterine glands

simple columnar lining


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UTERUSSECRETORY PHASE

functional layer thickens

glands become coiled and

accumulate large quantities of

secretory product



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UTERUSSECRETORY PHASE

functional layer thickens

glands coiled

UTERUS H&E

COILEDUTERINE

GLANDS

SECRETORY PHASE


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VAGINA

STRATIFIED SQUAMOUS EPITHELIUM

LAMINA PROPRIA

---------------- no glands ----------------

MUSCULARIS

INNER CIRCULAR

OUTER LONGITUDINAL

ADVENTITIA

MUCOSA


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Endocrinology of Pregnancy

To maintain the uterine endometrium and inhibitcontraction of myometrium, must maintain plasma

progesterone levels during pregnancy.

Early in pregnancy, this is accomplished by the

action of human chorionic gonadotropin (hCG) onthe corpus luteum (first 8 weeks of pregnancy).

Later in pregnancy, progesterone is produced bythe placenta.


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Actions of Human Chorionnic


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Actions of Human Chorionnic

Gonadotropin (hCG)

hCG binds to the LH receptor in the corpusluteum, maintaining luteal steroidogenesis during

the first 8 weeks of pregnancy.

In addition, hCG may act to stimulate testosteroneproduction from the developing testes in male

embryos.


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P t ti l R l f R l i i P t iti ?


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Potential Role of Relaxin in Parturition?

Relaxin acts on the cervix, causing dilatation andsoftening.

In some animals relaxin increases before laborstarts.

In humans, relaxin is high beginning early inpregnancy and stays elevated until labor.

Relaxin does act to soften connective tissues, suchas the ligaments connecting the pelvic bones, to

allow increase in size of the birth canal. Relaxin also decreases uterine contractility during

pregnancy.


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L i L i


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Lactation: Lactogenesis

Lactogenesis: secretion of milk from alveolarcells into the alveoli of the breast.

Stimulated by prolactin, and occurs after

parturition when estradiol and progesterone levels

are decreased.


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