Functional Histology of the Female

Reproductive System IDr. Stany Wilfred Lobo, PhDAssociate Professor Dept. of Anatomical SciencesEmail: dr.swlobo@yahoo.com

Functions of Ovary • Production of gametes: (oogenesis)

● Developing gametes are called oocytes● Mature oocytes are called ova (singular: ovum)

• Production of hormones:• Estrogens and Progestogens

• Growth and maturation of internal and external sex organs

• Female secondary sex characteristics that develop at puberty

• Breast development (ductal and stromal growth; accumulation of adipose tissue)

• Prepare uterus for pregnancy

• Composed of cortex and medulla• Medulla:

• central part• loose connective tissue• large contorted blood vessels,

lymphatics and nerves• Cortex:

● contains ovarian follicles embedded in rich cellular connective tissue• Scattered smooth muscle

fibers are present in stroma around follicles

Ovarian Structure

4

Surface of ovary is covered by single layer of cuboidal epithelium

• called germinal epithelium • Primordial germ cells are

extragonadal and migrate from embryonic yolk sac into cortex of ovary

• Tunica albuginea:• dense connective tissue

layer • between germinal

epithelium and cortex

Germinal epithelium

• Each follicle contains a single oocyte• Follicles distributed in stroma of the cortex• Early follicular stages occur during fetal life • primordial germ cells migrate to the primitive

gonads and differentiate to oogonia under the influence of genetic sex

• mitotic divisions greatly increase the number of oogonia

• Oogonia stop mitosis and become invested with follicular cells around 3rd month of gestation

• oogonia now called oocyte (invested in primordial follicle)

• oocytes initiate meiosis during fetal life • Arrested in prophase I• Remain dormant till puberty

Ovarian Follicles

• During puberty ovaries begin reproductive process• characterized by growth & maturation of

groups of follicles in each menstrual cycle• Normally, in each cycle only one oocyte reaches

full maturity • and is released in each cycle

• During the entire reproductive period approx. 400 mature ova are produced

Ovarian follicles cont

• During fetal life 5 million oocytes produced• At birth around 40 K are present

- rest are lost by ATRESIA• Around 400 are used during reproductive

period

Ovarian follicles cont

• Histologically 3 developmental types of follicles • PRIMORDIAL FOLLICLES• GROWING FOLLICLES :

• Primary follicles• Secondary (ANTRAL)

follicles• MATURE or GRAAFIAN

FOLLICLES

Follicle Development

• PRIMORDIAL Follicles:• Appear during 3rd

month of fetal development

• Found in stroma of cortex

• Single layer of squamous cells surrounds oocyte

• Outer surface of follicle cells has a basal lamina

Primordial follicle

Pr

Pr

• Oocyte enlarges• follicular cells become

cuboidal • As oocyte grows deeply

staining acidophilic layer, called ZONA PELLUCIDA, appears between follicle cells and oocyte

• ZP acts as sperm receptor

Primary follicle

15

• Rapid mitoses of follicle cells produces a stratified epithelium• MEMBRANA

GRANULOSA • Follicular cells are

now called GRANULOSA CELLS

Aleena Stephen

zona pellucida

• As granulosa cells proliferate• stromal cells immediately surrounding follicle

form a sheath of connective tissue • THECA FOLLICULI

• located external to basal lamina

Primary follicle cont.

• Theca differentiated into 2 layers:• THECA INTERNA

• inner, highly vascular layer of cuboidal secretory cells• EM appearance

of steroid secreting cells

• Have many LH receptors

• Produces estrogen

• THECA EXTERNA• outer layer of

connective tissue cells

• Contains smooth muscle cells and bundles of collagen fibers

• Boundaries between externa and stroma are indistinct

• Characterized by fluid-filled ANTRUM

• Follicle increases in size by proliferation of granulosa cells

• Factors required for oocyte and follicle growth:• Follicle-stimulating

hormone (FSH)

Secondary Follicle

• When granulosa layer reaches 6-12 cells thick• fluid-filled cavities appear

among granulosa cells• Fluid called LIQUOR

FOLLICULI (follicular fluid) • hyaluronic acid-rich

• Cavities coalesce to form a crescent-shaped cavity-Antrum

• Folllicle is now a secondary (ANTRAL) follicle

• The eccentrically positioned oocyte reaches 125 um diameter• undergoes no further growth• Oocyte maturation inhibitor (OMI)

secreted by granulosa cells into antrum

• OMI level progressively decreases as oocyte maturation increases

• as secondary follicles enlarge• antrum also enlarges

• lined by granulosa cells• Granulosum is uniform at the

wall of the follicle• Connected to the cells of the

follicle wall by• CUMULUS

OOPHOROUS

A

G

G

G

A

• Cumulus cells immediately surround oocyte called the CORONA RADIATA

• Granulosa processes increase in number • correlated with increased

LH receptors on antral surface

• Call-Exner Bodies• Secreted by granulosa cells• PAS+ bodies

extracellular among granulosa cells

• Contain hyaluronic acids and proteoglycans

• Mature follicle:• diameter of 10mm or

more• causes bulge on

surface of ovary• Granulosum thins as

antrum size increases

Development of Graafian Follicle

Corona radiata

• THECA layers become prominent• Lipid droplets in

cytoplasm• evidence for

steroid secretion• Normal level of LH

stimulates theca interna cells to secrete Estrogens

• Primary oocyte could be arrested from 12 to 50 years• In prophase of meiosis I• first meiosis initiated during the embryonic life• Completion of first meiosis occurs just before ovulation (in

response to LH surge)• Daughter cell with most cytoplasm now called:• SECONDARY OOCYTE (23 X)• measures 120-150 um diameter• Daughter cell with least cytoplasm – first polar

body (degenerates)• Secondary oocyte completes Meiosis II

only if fertilized

Ovulation

• Ovulation is process by which secondary oocyte is released from Graafian follicle

• Before ovulation blood flow stops in area of ovary surface called macula pellucida (Stigma)

• Oocyte with the surrounding cumulus cells is expelled

• Oocyte is guided to oviduct by fimbriae

Ovulation cont.

• Only 1 follicle is selected from a cohort of follicles to undergo maturation and ovulation• Releases secondary oocyte• Egg is viable in the female genital tract for 24 hours• Ectopic implantations might happens in the following

sites:• ovary surface• intestinal surface

- in both cases should be removed by surgery

• At ovulation about 45% of women experience midcycle sharp lower abdominal pain

• Related to smooth muscle cell contraction in the ovary• surge of LH

Ovulation cont.

• Occurs in ampulla of oviduct• Few hundred sperm (out of few millions) reach oviduct ampulla• Sperms undergo CAPACITATION

- an activation process that leads to vigorous motility- involve several biochemical changes and modification to sperm plasma membrane

• Capacitated sperm makes its way through corona radiata cells• Next, sperm binds to zona pellucida

– Triggers ACROSOME REACTION– acrosome enzymes released – sperm then penetrates zona pellucida and its membrane fuses with

the oocyte membrane• zona pellucida impermeable to other sperms

Fertilization

• Fusion of the membranes triggers resumption of meiosis II - secondary oocyte expels 2nd polar body and

becomes mature ovum ( 23 X) - DNA forms maternal pronucleus

• Sperm penetrates mature ovum - DNA forms male pronucleus

• Fusion of the male and female pronuclei forms a

ZYGOTE (46)

Fertilization cont.

• After ovulation the rest of the follicle differentiate into new functional unit, the CORPUS LUTEUM

• formed from granulosa and theca interna cells

• First Filled with blood from veins of theca interna

• called CORPUS HEMORRHAGICUM

• Then reorganizes into corpus luteum• Luteal cells increase in size • are filled with lipid droplets

Corpus Luteum

• After successful fertilization and implantation, corpus luteum secrete MAINLY progesterone• Depends for existence

on luteotropins mainly human chorionic gonadotropin (hCG) initially produced by the embryo and later by the placenta

Corpus Luteum of Pregnancy

• If fertilization and implantation do not occur corpus luteum will remain active ONLY for 14 days• This is called CORPUS LUTEUM

OF MENSTRUATION• Degenerates and involutes

• Corpus ALBICANS• Inactive white scar formed as

intercellular hyaline and collagenous material accumulates among degenerating cells

• will disappear after several months

Corpus Luteum of Menstruation