1. IN THE NAME OF GOD THE COMPASSIONATE THE MERCIFUL

2. Histology Lecture 22 Female Reproductive System

3. Female Reproductive System
Female reproductive system comprises of the following organs:
Ovaries
Oviducts
Uterus
Vagina
External Genitalia
Mammary Gland is a skin appendix but due to its close relation to reproductive system explains here

5. Ovary Ovaries are small almond shaped organs lying in pelvic cavities
The surface epithelium is simple cuboidal and known as germinal epithelium
Tunica albuginea is a dense irregular connective tissue that is directly beneath epithelium
The ovary can be divided into two components: cortex and medulla
Hilum is the route whereby vessels and nerves enter and leave the ovary
Medulla is the core of ovary contains loose connective tissue and vessels
Remnants of Wollfian ducts persists from embryonic period and are irregular tubules lined by a cuboidal epithelium

7. Ovary
Hilus cells are identical to Leydig cells, and may contain Reinke’s crystalloids
Small clumps of hilus cells are often found near blood vessels
Medulla contains stromal cells identical to those which are in the cortex
Cortex has two components a stroma and structures that producing gametes
Cortical stroma has closely packed spindle shaped fibroblast-like cells which are arranged in a whorled pattern
Collagen fibers between stromal cells are prominent in outer cortex and with time the amount of collagen will increase

10. Ovary
Stroma provides structural support, forms theca interna and externa around follicles, and secretes steroid hormone
There is three types of stromal steroid secreting cells:
Scattered luteinized stromal cells which are numerous during pregnancy
Stromal cells that form theca layers
Enzymically active stromal cells (EASC)which are numerous in postmenopausal women and secret testosterone

11. Ovarian Follicles
Ovarian follicles located in cortex and surrounded by stromal cells
A follicle consists of an oocyte surrounded by one or more layers of follicular cells
2 ovaries of young adult female have about 400,000 follicles; most of them will degenerate (atresia)
About 450 follicles will cycle to ovulation in lifetime

13. Types of Ovarian Follicles
According to morphological characteristic follicles can be categorized into:
Primordial Follicles
Growing Follicles
Unilaminar primary follicles
Multilaminar primary follicles
Secondary follicles
Mature Follicles (Tertiary or Graafian Follicles)

15. Primordial Follicle
Primordial follicles contain a primary oocyte that entered the prophase of first mitotic division
Primary oocyte surrounded with one layer of flattened follicular cells which are separated by a basal lamina from the stroma
Many of them degenerate during lifetime
Most numerous in fetus (several million)
One million at birth
At the onset of the buberty their number reduced to about a quarter of a million
Oocyte about 25 µm diameter
Euchromatic nucleus, large nucleolus

17. Growing Follicles Oocyte diameter increases to 100 to 150 µm
Nucleus enlarges and called germinal vesicle(GV)
Organelles increase in number and amount (mitochondria, several golgi complexes, RER, free ribosomes)
Follicular cells become cuboidal
Unilaminar primary follicle has one layer of cuboidal follicular cells
Multilaminar primary follicle has several layers of follicular (granulosa) cells

18. Growing Follicles
Zona pellucida secreted by oocyte and is composed of 3 glycoproteins ZP1, ZP2, ZP3 forms just outside oocyte membrane, thick basal lamina
Follicle cell filopodia extend into Zona pellucida as do oocyte microvilli, joined by gap junctions
Stromal cells differentiate into theca folliculi that has a theca interna and theca externa
A thickened basal lamina separated theca interna from granulosa cells

20. Theca Interna & Theca Externa
Cells are more cuboidal with round nuclei
steroid producing cell features
SER, mitochondria with tubular cristae and lipid droplets
produce androstenedione which is converted to estradiol by granulosa cells
highly vascularized
Theca externa
Composed of connective tissue and stromal cells with vessels forming a plexus
cells are flattened

21. Secondary Follicles Granulosa and theca cells increase in number
Fluid-filled spaces in granulosa layer fuse to form the antrum that become filled with liquor folliculi
This fluid is an exudates of plasma and produced by granulosa cells. It contains GAGs, proteoglycans, steroid binding protein, steroids and some hormones.
Cumulus oophorus is a small group of granulosa cells that surround primary oocyte and project into antrum
A single layer of granulosa cells that immediately surround the primary oocyte is known as corona radiata
Most of follicle at this stage become atretic
Some granulosa cells of atretic follicles do not degenerate and form interstitial glands which secret androgens

23. Mature (Graafian) Follicles
Mature follicle develops due to continued proliferation of granulosa cells and production of more liquor folliculi which undergo ovulation
By the time of ovulation it may be over 2.5 cm in diameter
Bulge from ovary surface
Because of continued formation of liquor folliculi cumulus oophorus detaches and float freely in liquor folliculi

26. Oocyte Meiotic Divisions
First meiotic division occurs just prior to ovulation under the influence of meiosis inducing factor
Second meiotic division then begins and stops at metaphase
Second meiotic division is completed after fertilization

27. Ovulation
Fluid pressure builds up until follicle ruptures due to formation of proteoglycans and hyaluronic acid and attraction of water
Before ovulation the surface of ovary loses its blood supply just where the follicle pressing it and known as stigma
Perifollicular connective tissue broken down by proteases
Ovum (Secondary oocyte) is drawn into open end of oviduct (fallopian tube)
Ovum remains viable about 24 hours after ovulation
Remnants of graafian follicle are converted to corpus hemorrhagicum

28. Corpus Hemorrhagicum Corpus Luteum
Following ovulation the remainder of follicle collapses and some ruptured blood vessels leak into follicular cavity and forming a clot that is known as corpus hemorrhagicum
Corpus Luteum
After removing the clot by phagocytes a temporary hormone secreting structure formed by granulosa cells and theca interna cells known as corpus luteum
Granulosa cells hypertrophy into large pale staining granulosa-lutein cells with organelles necessary for steroid production
They constitute about 80% of the cells of corpus luteum
These cells produce progesterone and convert androgen produced by theca-lutein cells into estrogens

30. Corpus Luteum
Theca interna cells form theca-lutein cells which are smaller and darker staining than granulosa-lutein cells
Located in folds of cells in perimeter of corpus luteum form about 20% of cells population and are highly vascularized
Produce estrogen, progesterone and androgens
If pregnancy does not occur corpus luteum of mensturation survives only days
In pregnancy it enlarges greatly due to HCG and lasts 6 months and called corpus luteum of pregnancy
Corpus luteum of pregnancy grows to a 5 cm diameter structure

33. Corpus Albicans
When the corpus luteum degenerate it is invaded by fibroblasts which manufacture collagen type I and form a fibrous structure known as corpus albicans
Large ones form after pregnancy and smaller ones after each ovulation
On the surface of ovary remnants of corpus albicans is visible as a scar

35. Oviduct Uterine tube is a muscular tube, 12 cm long
It is the site of fertilization
Upper end opens into peritoneal cavity near ovary
Lower end passes through the uterus wall
Oviduct has 4 segments
intramural part in uterine wall
isthmus is adjacent to uterine wall
ampulla is dilated part
infundibulum is funnel-shaped part near ovary with fimbriae

37. Oviduct
Mucosa has many longitudinal folds which are pronounced in the ampulla
Mucosa has a simple columnar epithelium consist of ciliated cell and nonciliated peg cell
Ciliated cells are numerous near ovarian end of the tube
Peg cells are secretory cells that produce a watery tubal fluid contains normal serum proteins, chloride and potassium ions
Cilia near ovary beat toward uterus but cilia near uterus beat toward ovary
Lamina propria composed of loose connective tissue

38. Oviduct
Muscularis consists of poorly defined Inner circular layer and outer longitudinal layer of smooth muscle cells
Muscularis peristaltic movements with the beating of the cilia of epithelium help to propel oocyte to the uterus
Serosa is a connective tissue layer lined by a simple squamous epithelium contains blood vessels, and nerves

41. Uterus
Uterus is a pear-shaped structure attached to oviducts at upper end and to vagina at lower end
Uterus is divided into three regions: Body Fundus Cervix
Wall of body and fundus has 3 layers
Endometrium
Myometrium
Adventitia/Serosa

43. Anterior portion of body covered by adventitia which is composed of areolar connective tissue
The remaining portion of uterus covered by serosa composed of a layer of simple squamous cells (mesothelium) resting on an areolar connective tissue

44. Myometrium
Myometrium is the thickest layer and composed of four poorly defined layers of smooth muscle separated by connective tissue
Inner and outer layers are mostly longitudinal in orientation
Middle layers are highly vascularized and consist of mostly circularly arranged bundle of smooth muscle cells
Arcuate arteries located in this layers and is known as Stratum Vasculare
Middle layers thicken during pregnancy with more and large smooth muscle cells (hyperplasia and hypertrophy) and increased collagen fibers
Myometrium is estrogen dependent in absent of estrogen smooth muscle cell atrophies and some of the begin to apoptosis

45. Endometrium
Endometrium is mucosal lining of uterus composed of a simple columnar epithelium
Epithelium has ciliated columnar cells and secretory columnar cells
Lamina propria composed of dense irregular connective tissue and vessels supports epithelium and houses simple tubular glands
The glands have not ciliated cells
Endometrium has 2 zones
Functional layer
Basal layer

47. Endometrial Layers
Functional layer is a thick superficial layer sloughed off during menstruation and replaced during each menstrual cycle
Functional layer vascularized by coiled helical arteries that originate from arcuate arteries in stratum vasculare
Basal layer is a deep narrow layer retained after menstruation whose glands epithelium and connective tissue element regenerate functional layer
Basal layer supplied by short straight arteries which originate from arcuate arteries in stratum vasculare

49. Menstrual Cycle
Estrogen and progesterone from ovary stimulate changes in the endometrium
The average menstrual cycle is 28 day
Begins age is about y/o and ends age is about y/o
The menstrual cycle has 3 main phases
Menstrual phase: days 1-4
Proliferative (follicular) phase: days 5-14
Ovulation around day 14
Secretory (luteal) phase: days 15-28

50. Proliferative (Follicular) Phase
Days 5-14 leading up to ovulation
Estrogen produced by theca cells of ovarian follicle
Cells of gland bases proliferate forming simple columnar epithelium and tubular glands of endometrium
Connective tissue cells proliferate in lamina propria
Coiled arteries grow into regenerated lamina propria
Functionalis of endometrium become 2-3 mm in thickness
glands have a straight tubes with narrow lumens but their cells accumulate glycogen
At the day 14 the functional layer has been fully restored

52. Secretory (Luteal) Phase
Begins after ovulation, days 15-28
Corpus luteum forms and produces progesterone
Glands develop further, become highly coiled, branched and begin to secrete
Coiled arteries also attain full development
Endometrium reaches 5 mm in thickness due to edema and accumulated glycogen secretions of the glands

54. Menstrual Phase
If fertilization does not take place the corpus luteum stops secreting hormones after about 14 days
Progesterone and estrogen decrease causing coiled arteries to intermittently constrict cutting off blood flow to the functional layer of endometrium
Endometrial cells die and the functional layer is sloughed off
Then coiled arteries dilate once again, because they are weakened they rupture
The disgorged blood removes patches of the functional layer as menses
Vessels distal to constrictions are shed with the functional layer causing some bleeding
About 35ml blood loss occur during mensturation

56. Uterine Cervix
Cervix is the lower part of uterus that protrude into vagina
It is lined by mucous secreting simple columnar epithelium
Part of cervix in upper vagina has stratified squamous nonkeratinized epithelium
Lamina propria composed of mostly dense connective tissue and many elastic fibers and a few smooth muscle cells
Mucosa do not slough off during menstruation
Cervical mucosa contains branched cervical glands
At time of ovulation cervical glands secrete a serous fluid
At other time the secretion become viscous and during pregnancy forming a plug
Softening of cervix during parturition is due to lysis of collagen

57. Vagina
A thick stratified squamous nonkeratinized epithelium lines the vaginal mucosa
Estrogen stimulates epithelium to synthesize glycogen
Mucosa has not glands but increment of fluid during sexual arousal is due to transudate from vessels of lamina propria and secretion of cervical glands
Underlying lamina propria composed of loose connective tissue that highly vascularized with many elastic fibers
Muscular layer of circular and a prominent longitudinal smooth muscle fibers
Adventitia of dense irregular connective tissue with elastic fibers, many vessels and vast venous plexus and nerves

59. Female Urethra Female urethra is about 5 cm in length
It is lined by transitional epithelium near bladder and stratified squamous nonkeratinized in reminder portion
Patches of pseudostratified columnar is interspersed
Lamina propria is a fibroelastic connective tissue
Mucous secreting glands of Littre are numerous along its length
Muscular layers is composed of an outer circular and an inner longitudinal smooth muscle fibers
When urethra pierce urogenital diaphragm a sphincter of skeletal muscle surrounds it

60. External Genitalia(Vulva)
External genitalia is consists of mons pubis, labia majora, labia minora, clitoris, Bartholin’s glands, minor vestibular glands, and hymen
Mons pubis is the are overlying symphysis pubis covered by skin that underneath it is a pad of fat
Labia majora are skin folds with an adipose core and a thin layer of smooth muscle
skin with coarse hair on their external surface, sweat and sebaceous glands, many nerve fibers
Labia minora are folds of skin without hair and with core of spongy connective tissue with elastic fibers
skin with sebaceous and sweat glands, and many nerve fibers

61. External Genitalia Clitoris is embryonic homologue of penis
contains 2 erectile tissue bodies
covered by stratified squamous epithelium
heavily innervated
Bartholin’s glands are mucous secreting glands with ducts opening into the vestibule of vagina
Minor vestibular glands are also opened into vestibule
Hymen is a thin fold of epithelially enclosed fibrovascular connective tissue that narrow the orifice of vagina in virgin

62. Mammary Glands
Mammary gland consists of lobes of compund tubuloacinar glands similar to apocrine sweat glands
Glands secrete by apocrine mechanism (lipids) and exocytosis (proteins)
Each lobe surrounded by dense irregular connective tissue and adipose tissue
Connective tissue surrounding acini has many plasma cells and lymphocytes, sources of milk immunoglobulins
Each lobe has its own duct leading into lactiferous ducts of nipple
Interlobular ducts have simple cuboidal epithelium surrounded by myoepithelial cells
Lactiferous sinuses lined by stratified squamous epithelium that changes to stratified columnar or cuboidal deeper in lactiferous ducts
Glandular cells proliferate during pregnancy

64. Areola & Nipple
Areola is a circular highly pigmented skin around nipple; color darkens during pregnancy due to increased melanin production by melanocytes
Areola contains sweat and sebaceous glands and also areolar glands of Montgomery that resemble both sweat and mammary glands
Nipple is a protuberance at the center of areola that is covered by stratified squamous keratinized epithelium
Terminal portion of lactiferous ducts end at nipple
The core of nipple is composed of dense collagenous CT with abundant elastic fibers connected to skin
Abundant smooth muscle fibers arrange in circular way around nipple and in longitudinal way along long axis of the nipple

66. Department of Histology
F.Rajaei