Master Femina Reproductive System

Microscopic Structures and Histophysiologis of Reproductive System

1. The Female Reproductive System,

2. The Male Reproductive System, The Fertilisation and Inplantation

dr. Yan Effendi Hasjim, DAHK.

Departement of Histology Sriwijaya University Faculty of Medicine 2013

Competencies
The student must be able to understand the:
1.
2. 3. 4.

5.
6. 7. 8. 9.

Structure and function of ovarium Development of a follicle Development of a corpus luteum Structural and functional of the uterine tube, Organization, structural and functional changes of the endometrium The histological features and functionsl of the cervix and vagina Structural and functional of placenta in pregnancy Histological features anf functional of the mammary gland The actions of the ovarian steroids on other organs of the body,

Component and Function of Reproductive System ?

Female Reproductive System
1.

Male Reproductive System

1.

Ovarium Development of a follicle ovulation Synthesis steroid hormon regulation of menstruation cyclus

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. 3.

Oviduct fertilisation migration of zygote Endometrium siklus menstruation inplatation pregancy partus Glands of Mamma lactation

4.

2.

Penis Male copulatory organ

Continuing generation

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)

Developed of femine reproductive system

incompletely developed INITIATION OF PUBERTY gonadotropic hormones secreted by the pituitary gland

1 million oogonia (primordial follicles)

MENARCHE Culminating of differentiation of the reproductive organs 300,000 to 400,000 follicles.

MENSTRUAL CYCLE (reproductive years) 450 oocytes released

MENOPAUSE the end of her reproductive years

OVARIUM

Maturation of Ovums
Primary Oocytes
oogonia in prophase stage of meiosis I
paracrine factors (meiosis-preventing substance) Follicular cells

arrested in the diplotene stage

meiosis-inducing substance (LH)

complete meiotic I until just before ovulation

Scondary Oocyte + first polar body (ovulasi)

Maturation of organs
primordial follicle
Before the onset of puberty, all of the follicles
LHRH (luteinizing hormone-releasing h) = GnRH (gonadotropin-releasing h) hypothalamus

release of LHRH is pulsatile, every 90 minutes,

half-life in the bloodstream is only 2 - 4 mnt.

initiating puberty. 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.

Microscopic Structure of Ovarium

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.

A. Ovarian Cortex
STROMA (interstitial compartment) Collagenous connective tissue,
INTERSTITIAL CELLS (fibroblast-like stromal cells)

OVARIAN FOLLICLES
1. 2. 3. 4. PRIMORDIAL FOLLICLES PRIMARY FOLLICLES SECONDARY FOLLICLES GRAAFIAN FOLLICLES

B. Ovarian Medulla
richly 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

A sudden surge of LH is released
uncharacterized local factors independent of FSH;

influence of FSH.

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

2. Follicle Primery Unilaminar / multilaminar

Primary oocyte prod. activin proliferative of follicular cells Zona pellucida Stromal cells, (multilaminar) theca

3. Fillicle Scundary
Primary oocyte, Granulosa cells, numerous layers

proliferation depends on FSH. liquor folliculi (Antrum)

Corona radiata : single layer.

4. Graafian (Mature) Follicles

cumulus oophorus (primary oocyte, corona radiata, follicular cells)

float freely within the liquor follic.

1. Primordial Follicles
primary oocyte single 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 .

Dependent of the Pituitary Gland

GnRH FSH

Theca internae Endocrine Cells of Stromal Cells

LH receptors Androstenedione estrogen estradiol

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

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

4. Graafian (Mature) Follicles

diameter 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

GnRH
FSH & LH

STROMAL CELLS
STROMA
Part of Ovarian Cortex interstitial compartment connective tissue,

INTERSTITIAL CELLS (fibroblast-like stromal cells)

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.

BASIC ORGANIZATION
Hypothalamus

GnRH
FSH LH

Pituitary Ovary
Estrogen Progesterone

Uterine tube

Uterus

Cervix

Vagina

Mammary gland

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.

FSH STIMULATE MATURATION SEVERAL PROMORDIAL FOLL

FOLL CELLS PROLIFERATE & SECRETE ESTRO (STIMULATE BY FSH)

FOLLICULAR CELL AQCUIRE LH RECEPTOR INITIAL LUTEINIZATION

SURGE OF LH SECRETION INDUCES OVULATION PERSISTENT LH INDUCES LUTEINIZATION RESIDUAL FOLL.CELLS & THECA INT. CELLS NO FERTILIZATION FSH & LH SECRESION DECLINES CORPUS LUTRHEUM REGRESSES

FOLICULAR DEVELOPMENT DEPENDS ON FSH LEVEL EARLY MENSTRUAL CYCLES, FSH INCREASE LH STIMULATES PRODUCTION OF ANDROSTENEDION (THECA INT.CELLS) FOLLICULAR CELLS ESTROGEN (THECA INTERNAL-FOLLICULAR CELLS SYNERGISM)

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

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 OVULATION PRODUCTION PROG, ESTRO, INHIBIN DECREASE FSH INCREASE GRADUALLY MESTRUATION

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 cells
increased blood flow to the ovaries edema. histamine, prostaglandins, collagenase are released in graafian follicle. proteolysis membrana granulosa Increased 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 Factors
14th 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

Corpus Luteum (Pasca ovulation)

remainder of the graafian follicle collapses, folded, ruptured blood vessels leak blood into the follicular cavity, corpus hemorrhagicum LH << corpus luteum menstr highly vascularized structure, granulosa-lutein cells (modified granulosa) theca-lutein cells (modified theca interna) secrete progesterone, androgens, estrogens. FSH <<

high levels of LH

Degeneration corpus luteum of menstruation preventing a second ovulation.

corpus luteum
theca-lutein cells (T) small

granulosa-lutein cells (G) large

corpus luteum of menstruation

nonfertilization fertilization corpus albicans.

corpus luteum degenerates phagocytosed by macrophages, fibroblasts enter, type I collagen
corpus luteum of pregnancy pregnancy, (hCG), secreted by the placenta placenta main site of production of the hormones corpus luteum for 3 months maintenance of pregnancy several months (see later).

OVIDUCT

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

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

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.

Mucosal
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

Serosa
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.

Muscularis

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

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

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

Structure of Uterus
a muscular organ (fundus, body, cervix).

1. ENDOMETRIUM
2. MYOMETRIUM 3. ADVENTITIA / SEROSA

ENDOMETRIUM

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

Vascularization of functional layer

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.

TWO LAYERS :
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

The menstrual cycle (a 28-day cycle)

Phae Follicular/pro liferasi

Phase Luteal/sekresi
1. PROLIFERATIVE

(FOLLICULAR/ESTROGEN ) PHASE 4-14

2. SECRETORY

(LUTEAL /PROGESTERON) PHASE 15 - 28

Estrogen Progesterone

3. MENSTRUAL PHASE 1- 4

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. ENLARGEDECIDUALLIKE

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

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

PROLIFERATIVE PHASE characterized 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),

SECRETORY thickening 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 PHASE characterized 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.

2. Myometrium
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.

Size of uterus

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 ?).

Contraction of uterine
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. Oxytocin (Pars nervosa) 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.

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.

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

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 viscosity of the cervical gland secretions.

Regulated by hormone (progesteron & estrogen)

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

CLINICAL CORELATION

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.

yan effendi hasjim 11.02.2013