SSN Histology

Female Reproduction

Comments to Patrick McCormick ()

I. The Ovary

1)  covered by cuboidal epithelium (aka "germinal epithelium")

a)  continuous with the mesothelium of the peritoneum

2)  tunica albuginea lies beneath epithelium, above ovarian cortex

a)  comprised of dense white fibrous CT

3)  follicular development

a)  cortex contains follicles

b)  follicular development stimulated by FSH

c)  in embryo, all follicles arrested after meiosis I diplotene stage

d)  at puberty, meiotic division completes

i)  secondary oocyte stops at meiosis II metaphase stage

e)  on fertilization, secondary oocyte completes meiosis, forms ovum & polar body

4)  ovulation cycle

a)  20 primordial follicles start cycle

i)  only one reaches maturity, others are atretic

5)  theca interna (round cells)

a)  highly vascularized layer of cuboidal secretory cells

b)  have lipid droplets and SER, characteristic of hormone producers

c)  stimulated by LH

i)  secrete androgen precursors of estrogen

d)  also has fibroblasts & collagen

6)  theca externa (spindle cells)

a)  smooth muscle cells

b)  collagen fibers

Follicular Development

Primordial Follicle / ·  resting stage from birth to puberty
·  primary oocyte surrounded by single layer of squamous granulosa cells
·  400,000 @ birth
·  zona pellucida (non-cellular) appears between oocyte and follicular epithelium, has glycoproteins
Early Primary Follicle / ·  growing stage
·  primary oocyte surrounded by single layer of cuboidal/columnar granulosa cells
Late Primary Follicle / ·  stratum granulosum: several layers of stratified columnar granulosa cells
·  gap junctions develop between granulosa cells, but no tight junctions (ZO), so no blood-follicle barrier
·  theca interna & theca externa form
Secondary (Antral) Follicle / ·  fluid-filled antrum develops in granulosa layer
·  requires FSH, IGF-I, Ca2+
·  oocyte maturation inhibitor (OMI) secreted by granulosa cells to stop oocyte growth
·  cumulus oophorus appears as mound of granulosa
·  corona radiata are cumulus cells that send microvilli through ZP to make gap junctions with oocyte
Mature (Graafian) Follicle / ·  very large
·  central atrium with oocyte off to side
Atretic follicles / ·  granulosa cell nuclei go apoptotic
·  cells loosen
·  glassy membrane from basal lamina, stains blue (trichrome)

Post Ovulation Follicle Stages

1)  corpus luteum (temporary endocrine gland)

a)  ruptured follicle fills with blood after ovulation

b)  walls collapse

c)  LH stimulates granulosa cells to enlarge, secrete progesterone

d)  theca interna secretes more estrogen to maintain uterine mucosa

e)  if implantation occurs, HCG from placenta is secreted to maintain CL

f)  if implantation fails, CL only active for 14 days

2)  corpus albicans

a)  CL progesterone inhibits LH secretion

i)  without placental rescue, CL becomes corpus albicans (white scar)

Uterine Tube (Fallopian Tube of Oviduct)

4 Sections from ovary to uterus

1)  Infundibulum

2)  Ampulla

a)  where fertilization occurs, longest segment

b)  highly fimbriated ("christmas tree") at mid-cycle

3)  Isthmus

4)  Uterine (intramural)

3 Layers throughout tube

1)  serosa - continuous with the broad ligament

2)  muscularis - thickens toward the uterine end; composed of smooth muscle

3)  mucosa - highly folded (most dramatically Q ampulla); composed of loose CT; 2 cell types

a)  ciliated cells (most)

i)  ciliary beating moves the ovum toward the uterus

ii)  the eosinophilic line at the base of the cilia are the basal bodies where the cilia insert

iii)  enlarge if estrogen appears

b)  non-ciliated peg cell

i)  secretes glycoproteins

ii)  stimulated by progesterone


Uterus - 3 layers

1) Perimetrium - external serous layer

2) Myometrium - smooth muscle, blood vessels, and lymphatics

3) Endometrium - mucosal layer that undergoes cyclical changes during the menstrual cycle

a simple columnar epithelium + 2 underlying layers

1) Stratum Basalis - adjacent to myometrium; not sloughed off during menses

2) Stratum Functionalis - big growth during cycle, sloughed off during menses

a) Stratum Spongiosum - broad, intermediate layer

b) Stratum Compactum - thinner, superficial layer

Vasculature of the uterus…

-branches of the uterine artery pass through the myometrium and divide into 2 types

1) Straight Arteries - short and supply Stratum Basalis; not very responsive to hormonal changes in menstrual cycle

2) Spiral Arteries - supply Stratum Basalis and Stratum Functionalis; distal portion (to S. Functionalis) is very responsive to hormonal changes; withdrawal of progesterone at the end of the cycle causes the spiral arteries to coitstrict, leading to ischemia and degeneration of Stratum Functionalis

Menstrual Cycle and the uterus.. .

-Proliferative Phase occurs at the end of menstruation; occurs with follicular maturation

-Estrogen stimulates and sustains

-early phase with thin endometrium (mainly Stratum Basalis) and base of uterine glands and spiral arteries

-later the endometrial stroma proliferates and becomes very vascularized; the glands proliferate and develop from simple tubular glands to numerous glands that begin secretion coincident to ovulation

-Secretory Phase begins with ovulation

-Progesterone (from the corpus luteum) stimulates glandular epithelium to synthesize glycogen (nutrition for fertilized ovum)

-saw tooth appearance of glands and big increase in size of Stratum Functionalis

-Menstruation occurs if no implantation

-Corpus luteum degenerates into Corpus Albicans, and no more progesterone

-lack of progesterone leads to constriction of spiral arteries and ischemia of Stratum Functionalis which then sloughs off

-Stratum basalis still receives blood from straight arteries and stays intact (not sloughed)

-If Fertilization occurs

-placenta secretes HCG which maintains both the Corpus Luteum and the continuation of Progesterone production

-Endometrium thus maintained

Cervix Uteri - 2 Areas

1) Cervical Canal - lined by simple columnar epithelium

-large, branched glands at mid-cycle, around owlation, giving more secretions to help sperm reach egg; otherwise prevents bacteria from entering cerviduterus

2 ) Portio Vaginalis - lined by stratified squamous epithelium (like vagina)

=portion of cervix that projects into vagina

-no glands (like vagina.. .)

****Note that a TRANSITION ZONE exists between the 2 areas described above

-abrupt transition in epithelium from simple columnar to stratified squamous

-may undergo malignant transformation, leading to CA of cervix

-it is important to take pap smears of this area..


SSN Histology

Female Reproduction System II

I. Histology of the placenta

A. Function of the placenta

1. gas exchange

2. nutrient absorption

3. excretion, ion regulation

4. protein synthesis

5. synthesis of gonadotropic and prolactin-like steroids

6. incomplete synthesis of progestins and estrogens

B. Trophoblast

cytotrophoblastic layer / syncytiotrophoblastic layer
single inner layer of stem cells / derived from fusion of
cytotrophoblastic cells, multinucleate
stains basophilic due to RER and polyribosomes / stains basophilic, contains smooth ER, lipid droplets, and tubular mitochondria to make steroids
distinct borders exist between cells / becomes increasingly broad, developing finger-like projections that actively invade the endometrium
mitotic figures can be seen (sometimes) / not mitotically active
secrete hCG (at first), and GnRH / secretes hCG, estrogen, and progesterone to sustain endometrial tissues

C. Decidual cells are derived from the maternal endometrium, they stain eosinophilic on H&E becauses of the numerous mitochondria

D. The placental barrier consists of six layers of tissue at all thicknesses and all stages of development:

1. syncytiotrophoblast (outermost layer, bathed in maternal blood)

2. cytotrophoblast (may be discontinuous)

3. basement membrane of the trophoblast

4. fetal connective tissue (mesoderm)

5. fetal endothelial cell basement membrane

6. fetal endothelial cells

**see Figure 1

E. Fetal Mesenchyme contains 2 major types of cells

1. fibroblasts - secrete connective tissue collagen

2. Hofbauer cells - phagocytotic, more common in the early placenta, with vacoules containing lipids, GAGS, and glycoproteins

F. Trends in the maturing placenta

1. tertiary villi are present (by 21 days) in all the slides; but as placenta matures, the villi branch

2. as the placenta matures, the fetal blood vessels become larger

3. increased collagen deposition in the fetal mesoderm

4. cytotrophoblast becomes increasingly sparse

5. increased numbers of syncitial knots, and thickened syncytiotrophoblast

II. Histology of the mammary gland

A. The breast contains 15-25 independent lobes. Each lobe is a compound-tubulo-acinar gland, embedded in a mass of adipose tissue and divided by dense connective tissue (less cellular) that is continuous with the dermis.

1. lobes are divided into lobules by intralobular septa, with loose connective tissue (more cellular) directly around the glandular elements

2. lobules also contain plasma cells (to secrete IgA), lymphocytes, fibroblasts, and myoepithelial cells (to contract and expel milk during lactation)

3. mammary glands are highly modified apocrine sweat glands that develop along the milk lines, from the axilla to the groin

4. lobes are well vascularized because hormones must be delivered to regulate glandular proliferation and secretion

5. lactiferous ducts extend from the secretory lobule to the nipple; near the nipple they are lined by squamous epithelium, changing to cuboidal near the secretory lobule

6. the nipple is well innervated, and contains dense fibrously arranged connective tissue with two layers of smooth muscle (radial and circumferantial layers deep to the nipple)

7. smooth muscle runs longitudinally along the lactiferous ducts

**see Figure 2

lactating mammary gland – slide #69 / post-menopausal mammary gland – slide #70
many secretory alveoli with large secretory cuboidal epithelial cells / few secretory alveoli, atrophy of glandular tissue
lipid in apical cytoplasm of secretory cells and ducts stained black by osmium tetroxide (apocrine secretion) / dense connective tissue and adipose
tissue replace glandular elements

B. Hormonal effects on mammary glands

1. mammary glands undergo hormonal changes at puberty and also with each menstrual cycle

2. at puberty, estrogen, GH, and glucocorticoids stimulate the growth of glandular tissue (mostly ducts)

3. at ovulation, estrogen stimulates secretory cells to increase in height, small amounts of fluid accumulate in the connective tissue

4. during pregnancy, progesterone stimulates proliferation of the secretory alveoli, and prolactin stimulates milk production

5. during lactation, oxytocin stimulates contraction of myoepithelial cells to eject milk into the ducts

C. Mechanisms of milk secretion - both apocrine and merocrine

1. merocrine secretion releases the protein component of milk, synthesized in RER, sent to the Golgi and packaged into granules that fuse with the plasma membrane to release

2. apocrine secretion releases lipid portion of milk; small lipid droplets coalesce into one. The droplet passes to the apical part of the cell, and takes part of the membrane & cytoplasm with it.