Female Reproductive Histology

7/29/2019 Female Reproductive Histology

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The Female Reproductive System

• Ovaries

• System of Genital Ducts

–

fallopian tubes

– uterus

– vagina

•

External Genitalia



Functions:

• production of female gametes

• reception of male gametes

•

provision of a suitable environment forfertilization

• development of fetus and its expulsion

•

nutrition of newborn



OVARY

• flattened ovoid bodies suspended on either side of the uterus on the lateralwall of the pelvic cavity

• gland of double function:

– exocrine (cytogenic)

– endocrine

• Hilum: – Vascular CT of the mesovarium becomes continuous with the ovarian

stroma

– Germinal epithelium:

• a layer of cuboidal cells that replaces the peritoneal covering of themesovarium

• a misnomer because it does NOT give rise to the primordial germcells

• a specialization of the peritoneal mesothelium resting on a thin basallamina



Ovary

• Tunica albuginea: a layer of dense CT beneath the peritonealmesothelium which increases in density with advancing age

• Has a cortex and a medulla



Ovary



Thick Outer CORTEX Thin Inner MEDULLA -Surrounds the medulla except at the hilumwhere the medulla becomes superficial -dense fibrocellular CT stroma -Few elastic fibers -Stroma

*swirly appearance *Ovarian follicles containing the oocytes

in various stages of development areembedded in this region

*Stromal cortical cells: -spindle shaped -resemble smooth muscle but nomyofilaments in their cytoplasm

-differentiates into ovarian interstitialcells, rich in lipid and resemble

lutein cells -aka., interstitial glands * fusiform shaped fibroblasts present

- Poor demarcation between the medulla andcortex

- plenty of loose fibroelastic CT - large convoluted, spiral, thick walled blood

vessels, lymphatics, and nerves - scattered strands of smooth mm - Berger’s cells (hilus cells)

*sympathicotrophic hilus glands *epithelioid cells associated with

vascular spaces & unmyelinated nerve*rich in lipids & crystals of Reinke *homologous with Leydig cells

-androgen secreting cells



GERM CELLS

• Located in the ovarian follicles at corticalregion of the ovary

• Germ cells: arise in the yolk sac and of endodermal in origin



r mor a o c e or n am narfollicle

• A big spherical cell, the ovum, surrounded by alayer of smaller flattened cells called thefollicular or granulosa cells

• Theca folliculi: condensation of dense CT aroundthe follicle

• Oocyte has an eccentrically placed nucleus with a large nucleolus, well developed golgi apparatus, surrounded by numerous small mitochondria



Primary Ovarian Follicle

• the growing follicles gradually move deeper into the cortex

• Characterized by:

– growth and differentiation of the ovum

– redistribution of organelles

–

Golgi complex becomes dispersed in the cytoplasm along theperiphery near the cell membrane or oolema

– RER becomes extensive & increased in free ribosomes

– Few lipid droplets

–

proliferation of follicular cells – becomes cuboidal or low columnar cells

– through mitosis, it forms a stratified epithelium (granulosacells)



Primary Ovarian Follicle

• Theca Folliculi: development of a CT capsule from thesurrounding stroma

– theca interna: highly vascular inner layer of secretory cells

– theca externa: outer layer composed of CT; penetrated by small

vessels; rich in collagenous fibers and fusiform cells

– Shows irregular microvilli on the surface of the oocyte intospaces between oocyte & surrounding granulosa cells

• Zona pellucida: – amorphous material deposited around the microvilli containing

mucoprotein substance – homogenous in fresh condition

– elaborated by the granulosa cells



Secondary Follicle(antral follicle)

• Antrum: a single cavity within the follicle formed from the fusion of smallspaces filled with fluid during the proliferation of follicular cells.

• Oocyte has reached its full size by the time the formation of antrum begins

• Cumulus oophorus

– Projection of follicular cells into the antrum forming an eccentric moundor hillock

– The follicular cells of the cumulus oophorus becomes radially arrangedand form the corona radiata, separated from the ovum only by zonapellucida

•

Membrana Granulosa: a regular continuous layer around the antral cavityformed by the stratified epithelium

• Call-Exner bodies: small accumulations of densely staining material thatappear among the granulosa cells with a (+) PAS reaction locatedextracellularly in EM



Mature Antral Follicle (GraffianFollicle)

• Requires 10 to 14 days from the beginning of the cycle

• Contains a large oocyte with large nucleus and prominentnucleoli

• occupies the full breadth of the cortex, and indents the medulla • Macula Pellucida: aka stigma, the t. albuginea and theca folliculi

are attenuated in the region where the follicle bulges on thefree surface of the ovary

•

Ovum has attained its full size, surrounded by a thick zonapellucida and a characteristic corona radiata

• coronal cells share communicating junctions both with eachother and with the oocyte



Graffian Follicle

• Granulosa cells: – stratified cuboidal epithelium with the basal layer of low columnar type

resting on a prominent basal lamina

– cells are small with irregular cell outlines and uniform nuclei

•

Theca folliculi: greatest development in the mature follicle – Theca interna:

• composed of large spindle-shaped or polyhedral cells with oval nuclei andfine lipid droplets in the cytoplasm

• contains rich capillary plexus

•

responsible for secretion of estrogen – Theca Externa

• composed of concentrically arranged fibers & fusiform cells of ABSENTsecretory function

• may have a significant role in post-ovulatory collapse of follicles



OVIDUCT OR FALLOPIAN TUBES

(UTERINE TUBES OR SALPHYNX) • Paired structures ~12 to 15 cm long and 6 to 8 mm in diameter • The end of the tube in relation to the ovary opens into the peritoneum,

while the other end

• opens into the uterine cavity

• Composed of T. Mucosa, T. Muscularis, T. Serosa

• Tunica Mucosa

– Thrown into characteristic longitudinal folds

• Ampulla: numerous elaborately branched folds

• Isthmus: short and rarely branched

• Interstitial part: Loxw folds

• Infundibulum: folds are continuous with the fringes



Oviduct



OVIDUCT

• Lining Epithelium: Simple columnar epithelium; ciliated or non-ciliated

– Peg Cells: non-ciliated cells secreting glycoprotein into the lumen toprovide nutrition to the ovum.

– Ciliated Cells: •

Greatest at the region of infundibulum and least at the isthmus • The cilia beat in the direction towards the uterus

• Epithelial cells: undergoes cyclic changes along with the uterinemucosa

• True glands are absent and there is no true muscularis mucosae

•

Tunica Muscularis: Inner circular or Spiral while Outer Longitudinal in arrangement

• Tunica Serosa: areolar CT

– Contains large blood vessels , lymphatics & nerves.

– Deeper layers contain longitudinal bundles of muscularis



UTERUS

• thick walled, hollow pear-muscular organ,flattened in a dorsoventral direction

• Anatomical Divisions:

– Upper expanded body or Corpus Uteri – fundus (rounded, dome-shaped top)

– Isthmus (narrow transition between the corpus & cervix)

– cervix (narrow neck whose terminal portion projectsto the vagina, i.e. portio vaginalis)



Uterus

• Muscularis or Myometrium – Shows changes only during pregnancy

– Massive coat of smooth muscle about 12 to 15 mmthick

– 3 layers: • Inner layer or sub-vascular stratum :

– longitudinally arranged

– absent in the cervix

• Middle layer or vascular stratum :

– thickest and forms the bulk of the muscularis

– composed of circular or spirally arranged muscle fibers

– with numerous blood vessels (i.e., veins) in the interstitium



UTERUS

– Outer layer or supra-vascular stratum :

» relatively thin

» composed of both circular and longitudinal fibers

» Longitudinal fibers becomes continuous with thelongitudinal muscle coat of vagina

– Fibers are shortest during the 1st week aftermenstruation & has the greatest length during the 4th week of the cycle

– During pregnancy, there is both an increase in musclelength and number.

– Cervix: has a firm consistency due to its dense fibrousnature



UTERUS

• Mucosa or Endometrium – Undergoes all the changes that take place in the

different phases of reproductive cycle

– Thin, pink, velvet-like membrane with perforations by

the ostia of the uterine glands

– Intermenstrual phase • Lined by simple columnar epithelium, ciliated & non-ciliated

cells

• Ciliated cells are located in discrete patches

• Non-ciliated cells exhibit secretory activity

• Epithelium rests on a delicate basement membrane and aconsiderably thick lamina propria with characteristicembryonal CT rich in fibroblasts



Normal Uterus



UTERUS

– Two principal layers:

• Stratum Functionalis

– Thick superficial portion

– Supplied with coiled arteries

– Subdivisions:

» Stratum compactum or superficial dense portion

» Stratum spongiosum or deeper portion of looser texture

• Stratum Basalis

– Thin deeper portion of the lamina propria

– Contains uterine glands and a network of straight coursed

capillaries that are independent from the blood vessels of thestratum functionalis

– The ONLY LAYER THAT REMAINS INTACT DURINGMENSTRUATION



UTERUS

• Uterine Glands

– Found in the lamina propria of the fundus & corpus of the uterus

– Slightly branched tubular glands extending to the

entire thickness of the endometrium to themyometrium

– Lined by simple columnar ciliated epithelium

– Secretes a thin alkaline fluid to keep the uterine

cavity moist



CERVIX

• CERVICAL GLANDS

– Large branched tubular glands lined by simplecolumnar mucous secreting cells that is affected byestrogen

– Branches of these glands are closed off from thelumen forming cyst-like dilatations filled with mucus,i.e. Nabothian cysts / follicles / ovules

– Spinnbarkait: property of cervical mucus that permitsit to be drawn out in long strands; which is maximalat the time of ovulation



Cervix



CERVIX

– Mucus:• change in the consistency of mucus from highly viscous state

to a less viscous, more highly hydrated at the mid-cycle

• Microscopic patterns:

– ‘fern-like pattern’ -7th to 18th day of menstrual cycle

– By day 21, there is no fern or palm leaf pattern

– During pregnancy, there is a “bladed or cellular appearance’

– Cervical mucosa does not participate in participate in menstruation and is thicker than the body of the uterus

– Plica palmitae or arbor vitae: numerous branchingfolds of the cervical mucosa



ENDOMETRIAL CYCLE

Pre-Menstrual or Ischemic interruption of coiled arteries

- 2-3 days before menstruation

- regression of corpus luteum d/t decrease estrogen & progesterone levels - stromal infiltration by PMN or mononuclear WBC - disintegration of reticular framework of stroma in the superficial layer - decrease thickness of endometrium d/t loss of fluid & secretion (2 days) - functional layer is pale d/t:

collapse of arteries & glands constriction of coiled arteries

- vasoconstriction of arterioles & coiled arteries precedes the onset of menstrual bleeding

superficial ½ to 2/3 of mucosa becomes inadequately supplied

Menstrual - external menstrual discharge: decrease in estrogen & progesterone endometrium undergoes involution & is partially destroyed bleeding maybe of either arterial or venous in origin upon hematoma formation, superficial endometrium is distended & ruptures

necrosis shed coiled arteries relax, bear the surface, the vessel walls break and blood is

added to the secretion hemorrhage stops when the coiled arteries vasocontrict again MENSTRUAL DISCHARGE

-35 ml; does not clot d/t presence of fibrinolytic enzymes -whole functional layer is lost -basal layer remains intact

-anovulatory type: cycle wherein bleeding is due to a non-production of a ripefollicle

sto og c c anges o



sto og c c anges oNormal 28 day cycle:

Days 14 to 16 Subnuclear glycogen rich vacuoles in the glands

17 to 18 Vacuoles have displaced the nuclei toward the middle of the cells

18 Mitosis ceases

20 Few vacuoles

20 to 21 Considerable interstitial edema

23 to 24 Predecidualization (increase in stromal cells, starts 1st in the region around spiral arteries)



•

Role of Prostaglandins: – Both endometrium & deciduas are enriched with

arachidonic acid

– Initiation of parturition & maintenance of Labor

– Menstruation in non-pregnant

– Mechanism is by induction of vasoconstriciton

• Menopause: – cessation of cyclic changes in the uterus

–

atrophic mucosa, fewer and shorter uterine glands(may appear cystic), lamina propria changes toareolar type

– Increased amount of fibrous tissue in the muscularcoat



• Cytotrophoblast – inner layer of cells withclearly defined cell boundaries

• Syncytiotrophoblast – outer layer of muti-nucleated protoplasmic mass

– Forms the primitive villi which are epithelial cordsextending out into the surrounding space

–

Chorion: • Primitive embryonic CT comes in relation with

trophoblast

• Chorionic or Secondary Villi: Embryonal CT with fetalblood vessels extending into the into the Villi

–

Chorion Leve: surface of the chorion degenerate by the3rd month of pregnancy

– Fetal component: deeply embedded (chorionfrondosum)

– chorionic plate: firm plate-like structure which is aportion of the chorion to which the villi are attached

D id G idit ti E d t i



• Decidua Graviditatis: Endometrium

– Decidua basalis or serotina - mucosa lyingbeneath the enbryo

•

maternal component of placenta • Site which is penetrated by the chorionic villi

– Decidua Capsularis or reflexa - mucosa betweenthe embryo & lumen of the uterus

– Decidua Parietalis or Vera – remaining mucosa of

body & fundus of uterus

• endometrium increase in early part of pregnancy

• glands enlarge & become more tortuous

• Decidual cells: large & rounded endometrialstromal cells – may contain two or more nuclei (large with sparse chromatin &

nucleoli)

–

Vesicular cytoplasm containg glycogen – rarely present by the end of pregnancy

PLACENTA



PLACENTAFETAL COMPONENT MATERNAL COMPONENT

-chorionic plate -chorionic villi 2 types of Villi

a. anchoring villi -pass from the chorionic plate to d. basalis

b. free or floating villi Structure of a villus has a central core of mesenchymal tissue

containing fetal blood vessels which are coveredby trophoblasts. Hofbauer Cells: large cells with spherical

nuclei found in the core of phagocytic function lined by typical endothelium

Trophoblasts covering the villus cellular trophoblast (cytotrophoblast)

1.inner layer of cell mass (undifferentriated) 2. a.k.a. Langhan’s layer

- consists of large, discrete pale cells - cytoplasm contains glycogen & vacuoles -desmosomes present

Syncytial trophoblast (syncytiotrophoblast) 1.outer layer next to the spaces filled with

maternal blood 2.dark layer of variable thickness showing

numerous small dark nuclei

3.absent intercellular boundaries

4.microvilli present on the outer surface 5.dense cytoplasm

(lysosomes & RER abundant)6.Syncytial sprouts or knots:

protuberances formed in the latter half of pregnancy as syncytiotrophoblasts

aggregate 7.Fibrinoid:

irregular masses of acidophilic homogenoussubstance present on the outer surface of the placenta

-decidua basalis *by the 4th month, it becomes loose in texture

due to rich venous plexus -decidual cells prominent during 1st half of pregnancy: smaller decidual cells contain glycogen protective role in preventing trophoblast

from penetrating into the myometrium(placenta acerata)

secretory role: prostaglandins & prolactin -glandular epithelium is rich in glycogen & lipiddroplets

-Placenta Septa: projections formed as the deciduas is deeplyeroded by the spiral arteries located opposite the anchoring villi

Placental Barrier: 1. Syncytial trophoblast separates the maternal

circulation from the fetal circulation. 2. Composed of: a. cytotrophoblast in the 1st trimester b. basal lamina of the trophoblast c. wall of the fetal blood vessels

(fetal CT, basal lamina of the fetalcapillaries, & fetal endothelium)

Placental Secretions: -human chorionic Gonadotropin

*maintenance of corpus luteum ofpregnancy

-placental Lactogen *stimulates milk synthesis

-progesterone & estrogen



Placenta: Chorionic Villi



VAGINA

•

hollow, musculo-fibrous organ, collapsedunder ordinary conditions

• Histological Divisions: – Mucosa

•Thrown into folds (rugae) and is lined by stratifiedsquamous non-keratinizing epithelium

• Glycogen: accumulated by epithelium, particularly at thetime of ovulation, thus appear vacuolated.

• Serves as a nutrient for male germ cell

•

Fermented by bacteria converting it into lactic acid,which is important in maintaining a suitable type of bacterial flora in the vagina

• During estrogen phase of the cycle, the vaginal fluid isacidic (lower pH) than at other times

• Tunica Propria: loose areolar CT which has papillae that

project towards the lining epithelium



Vagina



VAGINA

– In the anterior wall, there are less papillae while in theposterior wall, there are numerous

– Contains abundant elastic fibers & WBC

– Dense plexus of small veins are found in the deeperportion

–

Vaginal wall is devoid of glands. The mucus found in thelumen is derived from the glands of the cervix

– Muscular Coat • Smooth Muscle : Outer layer is longitudinally arranged

continuous with the myometrium while inner portion iscircular

• Skeletal Muscle: present at the level of introitus orostium which are fibers of the bulbocavernosus that actsas a sphincter

– Fibrosa or Adventitia: dense CT with many elasticfibers



FEMALE EXTERNAL GENITALIA

• Clitoris • Consists of two corpora cavernosa ending in a

rudimentary glans

• Composed of dense areolar CT rich in venous sinuses

• Genital corpuscles are present, thus is very sensitive

• Vestibule: • Vaginal and urethral openings are lined by stratified

squamous

• Skene’s glands or glandulae vestibulares minores

– Resemble the glands of Littre and contains mucous cells

– Located around the opening of the urethra and on theclitoris

• Bartholin’s Glands or vestibular glands major

– Tubuloacinar mucus secreting glands

– Homologous to the bulbo-urethral gland thus for

lubrication





• Labia MAJORA

– Contains large amount of subcutaneous adipose tissue andsmooth muscle similar to the dartos muscle

– general structure of skin

– Epidermis is thicker in the outer covering, more pigmented & contains several large hair follicles, sweat and sebaceous glands

– Undersurface epithelium is smooth & hairless

• Labia Minora – Stratified aquamous epithelium with tunica propria rich in elastic

fibers & blood vesseks

– No hairs but numerous sebaceous glands

• Hymen

– Lined by stratified squamous non-keratinized

–

Sensory Receptors • Meissner’s corpuscles: papillary region

• Genital Corpuscles in the sub-papillary region

• Lamellar or pacinian corpuscles: deeper portion of CT of the l. majora & clitoris

MAMMARY GLANDS



MAMMARY GLANDS

• specialized cutaneous glands located within thesubcutaneous tissue

• a fully developed mammary gland is similar to that of the sebaceous glands (modified sweat gland)

• Before puberty : mammary glands are similar in both

sexes, scanty fibrous stroma with few, short andnarrow blind ducts

• After puberty : in the female

– an increase in the CT stroma and accumulation of adipose

–

developed ductal system beyond the rudimentary stage & several branches start to appear

– Cluster of cells soon appear to differentiate into true alveoli



Resting Mammary Gland

• Parenchyma

– Scanty in a resting mammary gland

– Clusters of cuboidal or columnar cells at the end of the ducts separated by CT with fat cells

• Represents underdeveloped alveoli as there are NO truesecreting alveoli in the resting gland

– Myo-epithelial cells (basket cells• Resemble the fusiform smooth muscle cells

• Located between the secretory cells and the basal lamina

whose processes form loosely meshed basket – like anetwork enclosing the cells

• Contains parallel array of myofilaments, occasionalmitochondria and spindle shaped densities



Mammary glands during



Mammary glands during pregnancy

• In the first half of pregnancy, – Intralobular ducts undergo rapid proliferation & form

buds which enlarge into alveoli

– Decrease in interlobular fat & CT decrease in amount

– Decrease in Intralobular CT with lymphocyticinfiltrates

– Secretory alveoli • Lined by a single layer of columnar cells of granular &

acidophilic cytoplasm

• These cells rest on a basal lamina containing basket cells(myoepithelial cells)

• Develop first at the ends of the duct & gradually increase innumber

Mammary Glands



yResting Active



• Mammary glands after Lactation:



– Undergo retrogressive changes & returns to a resting statewith many alveoli containing remnants of secretory material

– The gland does not return to its nulliparous state

– CT & fat cells again become abundant – Involution of Ducts

• Mammary glands after menopause: – Progressive atrophy of both its parenchyma & CT stroma

– Epithelium & excretory ducts atrophy

– The gland returns to its pre-pubertal condition

– Involution of ducts

• -Male mammary gland: – Undergoes involution, with ducts but no alveoli or lobulation

Female Reproductive Histology

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