Master Femina Reproductive System

Microscopic Structures and Histophysiologis of Reproductive System

dr. Yan Effendi Hasjim, DAHK.

Departement of HistologySriwijaya University Faculty of Medicine

2013

1. The Female Reproductive System, 2. The Male Reproductive System,

The Fertilisation and Inplantation

The student must be able to understand the:

1. Structure and function of ovarium2. Development of a follicle 3. Development of a corpus luteum4. Structural and functional of the uterine tube, 5. Organization, structural and functional changes of the endometrium6. The histological features and functionsl of the cervix and vagina 7. Structural and functional of placenta in pregnancy 8. Histological features anf functional of the mammary gland9. The actions of the ovarian steroids on other organs of the body,

Competencies

Continuing generation

Component and Function of Reproductive System ?

Male Reproductive System

1. Testes Formation of the spermatozoa

Synthesis, storage, and release of the, testosterone (testes)

Form the noncellular portion of semen (seminal vesicles, prostate gland, bulbourethral glands of

2. Penis Male copulatory organ

Female Reproductive System

1. Ovarium Development of a follicle ovulation

Synthesis steroid hormon regulation of menstruation cyclus

2. Oviduct fertilisation migration of zygote

3. Endometrium siklus menstruation inplatation pregancy partus

4. Glands of Mamma lactation

introduction

The female reproductive system

1. INTERNAL REPRODUCTIVE ORGAN (ovaries, oviducts, uterus, vagina)

2. EXSTERNAL GENITALIA (clitoris, labia majora, labia minora).

3. MAMMARY GLANDS (not considered part of the female reproductive system)

incompletely developed

INITIATION OF PUBERTYgonadotropic hormones secreted by the pituitary gland

MENSTRUAL CYCLE(reproductive years)450 oocytes released

MENOPAUSEthe end of her reproductive years

Developed of femine reproductive system

1 million oogonia (primordial follicles)

MENARCHECulminating of differentiation of the reproductive organs300,000 to 400,000 follicles.

OVARIUM

Primary Oocytes oogonia in prophase stage of meiosis I

paracrine factors (meiosis-preventing substance)Follicular cells

arrested in the diplotene stage

(LH)meiosis-inducing substance

complete meiotic Iuntil just before ovulation

Scondary Oocyte + first polar body (ovulasi)

Maturation of Ovums

primordial follicleBefore the onset of puberty, all of the follicles

LHRH (luteinizing hormone-releasing h) = GnRH (gonadotropin-releasing h)

initiating puberty.

hypothalamus

release of LHRH is pulsatile, every 90 minutes, half-life in the bloodstream is only 2 - 4 mnt.

prerequisite• onset of menarche • maintenance of the normal ovulatory • maintenance normal menstrual cycles

throughout the reproductive life.

pulsatile release of gonadotropins (FSH and LH) the onset of the ovulatory cycle.

Maturation of organs

GERMINAL EPITHELUM: The surface epithelium, low cuboidal, (derived from the mesothelial)

TUNICA ALBUGENIA: irregular collagenous connective tissue capsule, dense, a poorly vascularized.

CORTEX : highly cellular (stromal cells). various stages of follicle development.

MEDULLA: richly vascularized loose connective tissue.

Microscopic Structure of Ovarium

A. Ovarian CortexSTROMA (interstitial compartment)

Collagenous connective tissue,

INTERSTITIAL CELLS (fibroblast-like stromal cells)

OVARIAN FOLLICLES 1. PRIMORDIAL FOLLICLES2. PRIMARY FOLLICLES3. SECONDARY FOLLICLES4. GRAAFIAN FOLLICLES

B. Ovarian Medullarichly vascularized fibroelastic connective tissue (large blood vessels, lymph vessels, and nerve fibers).

Interstitial cells, a few clusters of epithelioid cells that secrete estrogens.

Hilus cells a group of epithelioid cells, (=configuration and substances in cytoplasm as Leydig cells), secrete androgens.

Development of the Follicles

uncharacterized local factors independent of FSH;

influence of FSH.

A sudden surge of LH is released

1. Follicle Primolrdialprimary oocyte (arrested in prophase stage of meiosis I) single layer of flattened follicular cells

3. Fillicle ScundaryPrimary oocyte, Granulosa cells, numerous layers – proliferation depends on FSH. liquor folliculi (Antrum)– Corona radiata : single layer.

2. Follicle Primery Unilaminar / multilaminar Primary oocyte prod. activin proliferative of follicular cellsZona pellucida Stromal cells, (multilaminar) theca

4. Graafian (Mature) Follicles• cumulus oophorus (primary oocyte, corona radiata, follicular cells) float freely within the liquor follic.

1. Primordial Follicles primary oocytesingle layer of flattened follicular cells, desmosomes. basal lamina.

2. Primary Follicles

Primary oocyte activin proliferatie Follicular cells (unilaminar multilaminar) Zona pellucida: glycoproteins ZP1, ZP2, ZP3, ( oocyte) Filopodia of follicular cells & oocyte plasmalemma (gap junctions) theca

Theca interna, vascularized cellular layer, LH receptors androstenedione, in granulosa cells estrogen estradiol (by aromatase enzyme)

Theca externa, fibrous connective tissue

Independent of the Pituitary Gland

Zona Peluccida begins secrete by Prinmary Oocyte : glicoprotein ZP1,ZP2,ZP3

Stroma cells theca interna

3. Secondary (Antral) Follicles

Granulosa cells (follicular cells), numerous layers – proliferation depends on FSH. liquor folliculi

(Antrum)– Produce glycosaminoglycans, proteoglycans,

steroid-binding proteins – progesterone , estradiol , inhibin, folliostatin

(folliculostatin), and activin, regulate the release of LH and FSH.

– Corona radiata : single layer of granulosa cells Basement membrane between granulosa cells and theca interna .

Initial Antrum FormationLiquour folliculi: Hyaluronate, Steroid, Growth Factor, Gonadotropin progesterone , estradiol , folliostatin (folliculostatin) inhibin &activin, regulate the release of LH and FSH.

Theca internae Endocrine Cells of Stromal Cells

LH receptors Androstenedione estrogen estradiol

Dependent of the Pituitary Gland

FSH

GnRH

LHRH (luteinizing hormone-releasing h) = GnRH (gonadotropin-releasing h)

4. Graafian (Mature) Folliclesdiameter reach 2.5 cm (ovulation). Membrana Granulosa cells : in the wall of follicle Granulosa cells: form Cumulus oophorus (primary oocyte, corona radiata), float freely within the liquor folliculi

FSH& LH

GnRH

primary follicles multilaminar form theca

– Theca interna, cells possess LH receptors androstenedione, is converted into the estrogen estradiol (by aromatase)

– Theca externa, fibrous connective tissue.

STROMAL CELLSSTROMA

Part of Ovarian Cortex

interstitial compartment

connective tissue,

INTERSTITIAL CELLS (fibroblast-like stromal cells)

BASIC ORGANIZATION

GnRH

Pituitary

Ovary

FSHLH

Hypothalamus

EstrogenProgesterone

Uterinetube

Uterus Cervix Vagina Mammarygland

Hormonal Regulation of Ovarian Function

hypothalamo-pituitary Female Rep.Syst.

• FSH follicle cells

• LH, LHRH, theca cells

Follicle Liquour:

• FOLIOSTATIN INHIBIN suppress FSH release,

• ACTIVIN facilitates FSH release.

SURGE OF LH SECRETION INDUCES OVULATION

FOLICULAR DEVELOPMENT DEPENDS ON FSH LEVELEARLY MENSTRUAL CYCLES, FSH INCREASELH STIMULATES PRODUCTION OF ANDROSTENEDION (THECA INT.CELLS) FOLLICULAR CELLS ESTROGEN (THECA INTERNAL-FOLLICULAR CELLS SYNERGISM)

ESTROGEN & FSH FOLL.CELLS SYNTHESEIS LH RECEPTORLH FOLLIC.CELL PRODUCT PROGESTERON

FOLLICULAR CELL AQCUIRE LH RECEPTOR INITIAL LUTEINIZATION PERSISTENT LH INDUCES

LUTEINIZATION RESIDUAL FOLL.CELLS & THECA INT. CELLS

NO FERTILIZATION FSH & LH SECRESION DECLINES CORPUS LUTRHEUM REGRESSES

LH STIMULATE RAPIDLY LUTEINIZING FOLLICLE INCREASE SECRETIE PROG & ESTRO

HIGHT PROG & ESTRO INHIBITE LH & FSH SECRETION LH ABSENCE CORPUS LUTEUM LAST ONLY FEW DAYS (LH IS LUTEOTROPHIC)

NO PREGNANCY HIGHT PROG & ESTRO INHIBITE LH & FSH SE LUTEOLYSISI BEGIN & DAYS AFTER OVULATIONPRODUCTION PROG, ESTRO, INHIBIN DECREASE FSH INCREASE GRADUALLY MESTRUATION

FSH STIMULATE MATURATION SEVERAL PROMORDIAL FOLL

FOLL CELLS PROLIFERATE & SECRETE ESTRO (STIMULATE BY FSH)

Ovulation The process of releasing the SECONDARY OOCYTE from the graafian follicle

• ELEVATION OF BLOOD ESTROGEN TO LEVEL HIGHT (14th)

• secondary follicles• >> developing graafian follicle

following effects: Negative feedback of FSH release A sudden surge of LH is released by basophils cellsincreased blood flow to the ovaries edema. histamine, prostaglandins, collagenase are released in graafian follicle. proteolysis membrana granulosaIncreased level of plasminogen activator in follicles (catalyze enzyme) plasminogen to plasmin, proteolysis membrana granulosa, permitting ovulation

Physical factors (size & volume follicle)• pressing against the tunica albuginea stigma (avascular, blached )• connective tissue at the stigma degenerates, wall of the graafian follicle in contact with the stigma• opening between the peritoneal cavity and the antrum

Hormonal Factors14th day of the menstrual cycle elevation of blood estrogen to levels high

•developing graafian follicle & secondary follicles estrogen produced mostly •Negative feedback inhibition FSH release A sudden surge of LH is released•increased blood flow to the ovaries (edema)•collagenase are released in the vicinity of the graafian follicle proteolysis membrana granulosa

)

remainder of the graafian follicle collapses, folded, ruptured blood vessels leak blood into the follicular cavity,

• highly vascularized structure, • granulosa-lutein cells (modified granulosa) • theca-lutein cells (modified theca interna)• secrete progesterone, androgens, estrogens.

corpus hemorrhagicum

corpus luteum menstr

high levels of LH

LH <<FSH <<

Degeneration corpus luteum of menstruation

preventing a second ovulation.

Corpus Luteum (Pasca ovulation)

granulosa-lutein cells (G) large

theca-lutein cells (T) small

corpus luteum

corpus luteum of menstruation

nonfertilization

corpus luteum degenerates• phagocytosed by macrophages, • fibroblasts enter, type I collagen

corpus albicans.

pregnancy, (hCG), secreted by the placenta

corpus luteum of pregnancy

corpus luteum for 3 months maintenance of pregnancy

several months (see later). placenta

main site of production of the hormones

fertilization

OVIDUCT

anatomical regions: 1. INFUNDIBULLUM, open end is fringed: fimbriae. 2. AMPULLA, is where fertilization usually takes place. 3. ISTHMUS, is narrowed portion between ampulla and uterus. 4. INTRAMURAL, region passes through the uterine wall

a conduit for spermatozoa to reach the primary oocyte to convey the fertilized egg to the uterus.

1. The mucosa– longitudinal folds, >>ampulla,. – simple columnar epithelium. (Nonciliated Peg &

Ciliated cells )– The lamina propria; loose con.tissue

2. The muscularis smooth muscle. – poorly inner circular (I) and outer longitudinal

layers (O)

3. The serosal • simple squamous epithelium covering the

oviduct. • Loose con.tiss., blood vessels and autonomic

nerve fibers.

1. Columnar ciliated cells cilia, propelle toward the uterus. (the fertilized ovum, spermatozoa, the viscous liquid (the peg cells)

2. Peg cells (no cilia). a secretory function, providing a nutritive and protective environment

– capacitation of spermatozoa– ovum; embryo during the initial phases – inhibit microorganisms in the uterus

Mucosal

SEROSAL COVERING BY A SIMPLE SQUAMOUS EPITHELIUM. THE LOOSE CONECTIVE TISSUE, MANY BLOOD VESSELS & AUTONOMIC NERV FIBERS. – mostly large veins, contractions of the muscularis

during ovulation constrict the engorged veins. – distention of the entire oviduct brings the fimbriae

into contact with the ovary, capture of the released sc. oocyte.

Serosa

• smooth muscle. – poorly inner circular (I) – outer longitudinal layers (O)

• rhythmic contractions + the beating of the cilia, propel the captured oocyte to the uterus.

Muscularis

HISTOPHYSIOLOGY• RICHLY VASCULARIZED, MOSTLY LARGE VEINS MUSCULARIS

CONTRACTION DURING OVULATION VEINS CONSTRICTION • DISTENTION OF ENTIRE OVIDUST FIMBRAE CONTACT WITH OVARY

AIDING CAPTURE THE RELEASED SCONDARY OOCYTE• RHYTHMIC CONTRACTION OF MUSCULKARIS LAYER + BEATING OF CILIA

PROPEL OOCYTE TO UTERUS

UTERUS

FUNCTIONS:

• MENSTRUAL CYCLE (menstrual, proliferative (follicular), and secretory (luteal) phases).

• IMPLANTATION (the blastocyst becomes embedded in the uterine endometrium).

• PLACENTA DEVELOPMENT The placenta is a vascular tissue derived from the uterine endometrium as well as from the developing embryo.

• EXPEL FETUS & PLACENTA DURING DELIVERY Powerful, rhythmic contractions of the pregnant uterus during delivery expel the fetus and later the placenta from the uterus

a muscular organ (fundus, body, cervix).

1. ENDOMETRIUM

2. MYOMETRIUM

3. ADVENTITIA / SEROSA

Structure of Uterus

SIMPLE COLLUMNAR EPITHELIUM– Nonciliated (secretory )columnar cells – ciliated cells,

LAMINA PROPRIA– dense, irregular collagenous

connective tissue, highly cellular, – simple branched tubular glands,

extend as far as the myometrium, no ciliated cells .

– richly vascular

ENDOMETRIUM

1. COILED HELICAL ARTERIES from arcuate arteries of the stratum vasculare, (middle layer of the myometrium). a rich capillary network

supplies the glands and connective tissue

2. STRAIGHT ARTERIES from the arcuate arteries , much shorter,

supply only the basalis layer.

Vascularization of functional layer

FUNCTIONALIS LAYER

• thick, superficial, sloughed at menstruation • AFFECTED BY CHANGE OF PROG & ESTROG• BLOOD SUPPLY FROM SPIRAL ARTERIAL• PARTIAL/TOTAL LOST AFTER MENSTRUATION

BASALIS LAYER narrow, glands and connective tissue elements proliferate regenerate

• NOT AFFECTED BY CHANGE OF PROG & ESTROG• BLOOD SUPPLY FROM DRIVES BASAL ARTERIE

THAN SPIRAL ARTERIAL (stright arteri)• NOT LOST REGENERATION

TWO LAYERS :

Estrogen

Phae Follicular/proliferasi

Phase Luteal/sekresi

Progesterone

1. PROLIFERATIVE (FOLLICULAR/ESTROGEN ) PHASE 4-14

2. SECRETORY (LUTEAL /PROGESTERON) PHASE 15 - 28

3. MENSTRUAL PHASE 1- 4

.

The menstrual cycle (a 28-day cycle)

EARLY PROLIF PERIOD, GLDS SHORT, STRIGHT, NARROW, LB COMPACTED

MIDPROLIF. GLD LONGER, STRIGHT, EPITH MITOTIC, LP SLIGHT EDEMA

LATEPROLIF, MITOTIC INTENSE, GLD TORTUOUS, LP MORE EDAMATOUS

MIDSECRETORY PERIOD. GLYCOGEN ACCUMULATES IN BASAL EPITH GLD, SAWTOOTHED APPEARANCE OF GLD, STROMA CELLS SUROUND SPIRAL ART. ENLARGE”DECIDUAL-LIKE”

ISCHEMIC PERIODE, UPPER REGION STRUMA CONTAIN NUMEROUS DECIDUA CELLS. SPIRAL ART CONTRACT ISCHEMIC STARTS

FINAL DAY OF CYCLE, GLYCOGEN SHIFT TO APICAL CELLS, SECRETION IN LUMEN, STROMAL CELL MITOTIC ALY, DECIDXUAL CHANGE

PROLIFERATIVE PHASEcharacterized by – reepithelialization– reconstruction of the glands, connective tissue,

and the coiled arteries renewal of the functionalis.

at the same time as the development of the ovarian follicles (follicular phase),

SECRETORYthickening of the endometrium – edema– accumulated glycogen secretions, – highly convulted and branched glds

secretory granules: accumulate in the apically released into the glands lumen . glycogen-rich material nourish the conceptus before formation of the placenta. after ovulation.

MENSTRUAL PHASEcharacterized by the desquamation of the functionalis layer. the corpus luteum becomes nonfunctional (14 days after ovulation), thus reducing the levels of progesterone and estrogen.

Hormonal Regulation of Ovarian Function and menstrual cycle

Function of hormones in menstrual cycle

Correlation of follicular development, ovulation, hormonal interrelationships, and the menstrual cycle.

levels of estrogen and luteinizing hormone (LH) are highest at the ovulation.

three layers of smooth muscle.

1. inner Longitudinal muscle

2. middle circular layer (richly vascularized : arcuate arteries stratum vasculare).

3. outer Longitudinal layers,

narrows toward the cervix, the amount of muscle tissue diminishes and is replaced by fibrous connective tissue.

At the cervix, dense, irregular connective tissue containing elastic fibers and only a small number of scattered smooth muscle cells.

2. Myometrium

Size and number of the muscle cells are related to estrogen levels.

Pregnancy: estrogen levels >> largest and most numerous

After menstruation , estrogen levels are low./absent, smallest (atrophies)

During pregnancy – increase in size is related to hypertrophy cells (population also

increases, suggesting that hyperplasia also occurs). – the increase in cell number results only from division of smooth

muscle cells or also from differentiation of undifferentiated cells into smooth muscle fibers ?).

Size of uterus

Sexual stimulation moderate uterine contractions.

During menstruation, may be painful

During labor : Powerful, rhythmic contractions expel delivery the fetus and later the placenta from the uterus.

Contraction of uterine

The process of uterine contractions during parturition is due to hormonal actions:

Corticotropic hormone, the myometrium and the fetal membranes produce prostaglandins. Prostaglandins and oxytocin uterine contractions.

After delivery, oxytocin continues to stimulate uterine contractions, inhibit excessive blood loss from the detachment site of the placenta.

Oxytocin(Pars nervosa)

CERVIX UTERUS

Cervix

Epithelium:

Internal surface : mucus-secreting simple columnar,

External surface stratified squamous nonkeratinized (= vagina).

Cervical glands :

branched cervical glands.

mucosa changes during the menstrual cycle, but does not slough during menstruation.

EPITHELIUM: a mucus-secreting simple columnar, a stratified squamous nonkeratinized (similar to the vagina).

CERVICAL GLANDS: branched cervical glands. THE WALL : >> dense collagenous connective tissue,

many elastic fibers few smooth muscle fibers. At parturition,, relaxin (luteal hormone), lysis of collagen a softening of the cervix, facilitating cervical dilation.

The cervix-the terminal end of the uterus-extends (protudes) into vagina.

progesterone regulates the viscosity of the cervical gland secretions. ESTROGEN LESS VISCOUS

At the midpoint in the menstrual cycle, (ovulation), a serous fluid facilitates entry of the spermatozoa

At other times, (during pregnancy), more viscous preventing the entry of sperm and microorganisms

The viscosity of the cervical gland secretions.

Regulated by hormone (progesteron & estrogen)

Cervical carcinoma most common cancers in women, (rare in virgins and in nulliparous) multiple sex partners and herpes infections, incidence >. develops from the stratified squamous nonkeratinized (exsternal surface)

carcinoma in situ. (detected early, successfully treated with surgery)Invasive carcinoma (invade other areas and metastasize, a poor prognosis).

The Papanicolaou ("Pap smear") technique diagnostic tool detecting cervical cancer. aspirating cerviculal fluid from the vagina or scrapings directly from the cervix. prepared and stained on a microscope slide variations in the cell populations to detect anaplasia, dysplasia, and carcinoma.

CLINICAL CORELATION

yan effendi hasjim11.02.2013