The Female Reproductive System

Ovaries System of Genital Ducts

fallopian tubes uterus vagina

External Genitalia

The notes compiled in this will guide you in histology. This is just one little way to help you breeze through medical school. As a favor, PLEASE DO NOT REPRODUCE =(

Functions:
production of female gametes reception of male gametes provision of a suitable environment for fertilization development of fetus and its expulsion nutrition of newborn

OVARY
flattened ovoid bodies suspended on either side of the uterus on the lateral wall 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 the mesovarium a misnomer because it does NOT give rise to the primordial germ cells a specialization of the peritoneal mesothelium resting on a thin basal lamina

Ovary
Tunica albuginea: a layer of dense CT beneath the peritoneal mesothelium which increases in density with advancing age Has a cortex and a medulla

Ovary

Thick Outer CORTEX

-Surrounds the medulla except at the hilum where the medulla becomes superficial -dense fibrocellular CT stroma -Few elastic fibers -Stroma *swirly appearance *Ovarian follicles containing the oocytes in various stages of development are embedded in this region *Stromal cortical cells: -spindle shaped -resemble smooth muscle but no myofilaments in their cytoplasm -differentiates into ovarian interstitial cells, rich in lipid and resemble lutein cells -aka., interstitial glands * fusiform shaped fibroblasts present

Thin Inner MEDULLA

- Poor demarcation between the medulla and cortex - plenty of loose fibroelastic CT - large convoluted, spiral, thick walled blood vessels, lymphatics, and nerves - scattered strands of smooth mm - Bergers 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 cortical region of the ovary Germ cells: arise in the yolk sac and of endodermal in origin

Primordial follicle or Unilaminar follicle

A big spherical cell, the ovum, surrounded by a layer of smaller flattened cells called the follicular or granulosa cells Theca folliculi: condensation of dense CT around the 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 the periphery 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 (granulosa cells)

Primary Ovarian Follicle

Theca Folliculi: development of a CT capsule from the surrounding 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 into spaces 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 small spaces 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 mound or hillock The follicular cells of the cumulus oophorus becomes radially arranged and form the corona radiata, separated from the ovum only by zona pellucida Membrana Granulosa: a regular continuous layer around the antral cavity formed by the stratified epithelium Call-Exner bodies: small accumulations of densely staining material that appear among the granulosa cells with a (+) PAS reaction located extracellularly in EM

Mature Antral Follicle (Graffian Follicle)

Requires 10 to 14 days from the beginning of the cycle Contains a large oocyte with large nucleus and prominent nucleoli 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 the free surface of the ovary Ovum has attained its full size, surrounded by a thick zona pellucida and a characteristic corona radiata coronal cells share communicating junctions both with each other 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 and fine lipid droplets in the cytoplasm contains rich capillary plexus responsible for secretion of estrogen

Theca Externa
composed of concentrically arranged fibers & fusiform cells of ABSENT secretory 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 nonciliated
Peg Cells: non-ciliated cells secreting glycoprotein into the lumen to provide 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 uterine mucosa 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 projects to the vagina, i.e. portio vaginalis)

UTERUS
Histological Divisions:
Perimetrium or Serosa
Peritoneal layer of broad ligament covering the corpus & a portion of the cervix Composed of a single layer of mesothelial cells supported by a thin CT layer that is firmly adherent to the muscular layer Constant all throughout the cycle

Uterus
Muscularis or Myometrium
Shows changes only during pregnancy Massive coat of smooth muscle about 12 to 15 mm thick 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 the longitudinal muscle coat of vagina

Fibers are shortest during the 1st week after menstruation & has the greatest length during the 4th week of the cycle During pregnancy, there is both an increase in muscle length and number. Cervix: has a firm consistency due to its dense fibrous nature

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 & nonciliated cells Ciliated cells are located in discrete patches Non-ciliated cells exhibit secretory activity Epithelium rests on a delicate basement membrane and a considerably thick lamina propria with characteristic embryonal CT rich in fibroblasts

Normal Uterus

Non-pregnant Uterus

Pregnant 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 the stratum functionalis The ONLY LAYER THAT REMAINS INTACT DURING MENSTRUATION

UTERUS
Vascular Architecture:
Uterine & Ovarian arteries arcuate arteries (middle third of uterine wall) radial arteries coiled or spiral arteries & basal arteries Coiled or Spiral arteries
Supplies most of the the mid portion & ALL of the superficial third of the endometrium Walls of these vessels are sensitive to the action of hormones Show pronounced modifications during menstruation

Straight basal endometrial arteries

Smaller in caliber and length than the coiled arteries Extend only into the basal layer Not responsive to hormones Do not undergo changes during menstruation

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 the myometrium Lined by simple columnar ciliated epithelium Secretes a thin alkaline fluid to keep the uterine cavity moist

CERVIX
Lining Epithelium: tall columnar non-ciliated mucous secreting epithelium
at the level of internal os, ciliated cells are occasionally seen at the level of external os, an abrupt change to stratified squamous epithelium is seen that is similar to the vaginal epithelium

Tunica propria: less cellular than those of fundus and body; contains many collagen & elastic fibers & cervical glands

CERVIX
CERVICAL GLANDS
Large branched tubular glands lined by simple columnar mucous secreting cells that is affected by estrogen Branches of these glands are closed off from the lumen forming cyst-like dilatations filled with mucus, i.e. Nabothian cysts / follicles / ovules Spinnbarkait: property of cervical mucus that permits it to be drawn out in long strands; which is maximal at 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 midcycle 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 branching folds of the cervical mucosa

CERVIX
Muscular Coat: thinner than that of the body of the uterus and fewer blood vessels present Fibrous Coat: Loose Areolar CT Portio Vaginalis:
stratified squamous epithelium rich in glycoprotein from a tall columnar epithelium of the endocervix Site of Cervical CA (Papanicolaou Smear: desquamated cells from the vagina and cervix are examined microscopically for CA detection)

STAGE

ENDOMETRIAL CYCLE
HIGHLIGHTS

Proliferative or Follicular Early

follicular growth & estrogen secretion period varies greatly - thin endometrium - narrow tubular glands of straight course toward the basal layer epithelium is low columnar with round nuclei stromal cells are packed densely with small deep staining nuclei * in the superficial layer, these cells are packed loosely, rounded, vesicular, and has larger nuclei 2-3 days after ovulation, mitotic figures appear in the gland no lymphocytic infiltration - glandular hyperplasia glandular epithelium is taller & pseudostratified by ovulation - increase in stromal ground substance - thicker endometrium progestational stage active corpus luteum - endometrium thickness decrease d/t loss of fluid 3 zones become well-defined *basal zone (layer adjacent to myometrium) *Spongy zone (layer between the compact & basal layers) undergoes little histologic changes during menstruation mitosis in the glands present lacy labyrinth with scanty stroma between the tortuous glands (characteristic of the luteal phase) *Compact Zone (immediately beneath the endometrial surface) thickening of endometrial stroma (d/t edema) - glands are nearly straight & narrower in the compact & superficial layer with the lumen often filled with secretions - endometrium (5-mm thick) is extremely vascular, succulent & rich in glycogen - Stromal cells (fibroblasts, PMN, macrophages, lyphocytes & monocytes) undergo hypertrophic changes - appearance of spiral or coiled arteries becoming more tortuous & dilated)

Late

Secretory or Luteal Early

Late

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 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 ripe follicle

Days 14 to 16

Histologic changes of Normal 28 day cycle:

Subnuclear glycogen rich vacuoles in the glands Vacuoles have displaced the nuclei toward the middle of the cells Mitosis ceases

17 to 18

18

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 to areolar type Increased amount of fibrous tissue in the muscular coat

UTERUS During Pregnancy

by the 6th day, implantation in the endometrium occurs (blastocyst stage) lumen & glandular cells appear large, containing glycogen, mucinogen, & some lipids endometrium is thick & edematous Blastocyst
Trophoblast a single layer of cells comprising the wall
becomes several layers as it implants by the eleventh day, it consists of 2 layers (cytotrophoblast & syncytiotrophoblast)

 Cytotrophoblast inner layer of cells with clearly defined cell boundaries Syncytiotrophoblast outer layer of mutinucleated protoplasmic mass
Forms the primitive villi which are epithelial cords extending out into the surrounding space Chorion:
Primitive embryonic CT comes in relation with trophoblast Chorionic or Secondary Villi: Embryonal CT with fetal blood vessels extending into the into the Villi
Chorion Leve: surface of the chorion degenerate by the 3rd month of pregnancy Fetal component: deeply embedded (chorion frondosum) chorionic plate: firm plate-like structure which is a portion of the chorion to which the villi are attached

 Decidua Graviditatis: Endometrium

Decidua basalis or serotina - mucosa lying beneath the enbryo
maternal component of placenta Site which is penetrated by the chorionic villi

Decidua Capsularis or reflexa - mucosa between the 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 endometrial stromal cells
may contain two or more nuclei (large with sparse chromatin & nucleoli) Vesicular cytoplasm containg glycogen rarely present by the end of pregnancy

PLACENTA
FETAL 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 covered by 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. Langhans 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 homogenous substance present on the outer surface of the placenta

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 fetal capillaries, & fetal endothelium) Placental Secretions: -human chorionic Gonadotropin *maintenance of corpus luteum of pregnancy -placental Lactogen *stimulates milk synthesis -progesterone & estrogen

-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 & lipid droplets -Placenta Septa: projections formed as the deciduas is deeply eroded by the spiral arteries located opposite the anchoring villi

Placenta: Chorionic Villi

Umbilical Cord

VAGINA
hollow, musculo-fibrous organ, collapsed under ordinary conditions Histological Divisions:
Mucosa
Thrown into folds (rugae) and is lined by stratified squamous non-keratinizing epithelium Glycogen: accumulated by epithelium, particularly at the time 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 is acidic (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 the posterior wall, there are numerous Contains abundant elastic fibers & WBC Dense plexus of small veins are found in the deeper portion Vaginal wall is devoid of glands. The mucus found in the lumen is derived from the glands of the cervix

Muscular Coat
Smooth Muscle : Outer layer is longitudinally arranged continuous with the myometrium while inner portion is circular Skeletal Muscle: present at the level of introitus or ostium which are fibers of the bulbocavernosus that acts as a sphincter

Fibrosa or Adventitia: dense CT with many elastic fibers

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 Skenes glands or glandulae vestibulares minores
Resemble the glands of Littre and contains mucous cells Located around the opening of the urethra and on the clitoris

Bartholins Glands or vestibular glands major

Tubuloacinar mucus secreting glands Homologous to the bulbo-urethral gland thus for lubrication

FEMALE EXTERNAL GENITALIA

Labia MAJORA Contains large amount of subcutaneous adipose tissue and smooth 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 Meissners 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
specialized cutaneous glands located within the subcutaneous 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 and narrow 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

 Compund tubulo-alveolar gland of 15 to 20 irregular lobes

Each lobe is divided into several lobules
Main Lactiferous duct

Resting Mammary Gland (breast of a sexually mature non-pregnant woman)

lined by stratified squamous epithelium Lactiferous sinus: dilatation near its termination at the summit of the nipple gives off branches that drain lobules Intralobular ducts Lined by a single layeR of columnar cells Smaller ducts are lined by a double layer of cuboidal cells Smallest ducts are connected to the alveoli (alveolar ducts) Duct opens at the apex of the nipple

Resing Mammary Gland

Interlobar septa: dense CT separating the lobes
Suspensory Ligaments of Cooper: Dense fibrous trabeculae Stroma is both fibrous and fatty in nature
Fat surround the gland in the deeper regions and superficially (except at the areola) Few fat droplets are present within the gland

Interlobular CT: dense type

More cellular, fewer collagenous fibers and almost no fat Loose CT surrounding the duct system permits greater distensibility when it undergoes hypertrophy

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 true secreting 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 a network enclosing the cells Contains parallel array of myofilaments, occasional mitochondria and spindle shaped densities

Resting Mammary Gland

-Nipple & Areola 1. contains long dermal papilla with blood capillaries 2. smooth muscles oriented longitudinally along the lactiferous ducts and circumferentially both within the nipple and around its base 3. Areolar glands of Montgomery or glands of duval a. big modified sweat glands around the nipple in the areolae 4. tip of the nipple is supplied with free nerve endings and meissners corpuscle.

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 lymphocytic infiltrates 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 in number

Mammary Glands Resting Active

 Later months of pregnancy Breast Enlargement: hypertrophy of parenchymal cells distention of the alveoli with a eosinophilic secretion, colostrums Colostrum: secretion formed during the first few days after parturition Contains cellular debris, including cells of probable leukocytic origin, large fat globules, and more Immunoglobulins than milk Secretory Alveoli: Varies from tall epithelium to low columnar cells If tall: distal ends separated projecting into the lumen, with more organelles If short: smooth surface, granular-slightly acidophilic cytoplasm, few mitochondria Lumen is crowded with lipid droplets & fine granular material Apocrine in nature (partial disintegration) Milk Protein component: merocrine Secretion Fat component: Apocrine secretion CT stroma is greatly thinned Ducts are numerous Milk Let down: Oxytocin

 Mammary glands after Lactation:

Undergo retrogressive changes & returns to a resting state with 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