Histology of the Female Reproductive System

Female Reproductive System: 4 major functions

(1) Produce eggs (oocytes) and steriodal hormones (estradiol, progesterone, etc.)

(2) Receive and transport eggs and sperm (sperm capacitation and fertilization)

(3) Provide a suitable environment for fertilization and development of the fetus

(4) Expel the developed fetus to the external environment (via smooth muscle contraction under hormonal control)

Ovary – the site of oogenesis

Morphology – paired organs lying on either side of the uterus adjacent to the lateral uterine wall

3-5cm long, flattened ovoid shape; encapsulated by a fibrous tissue layer (tunica albuginea)

Inner Medulla (Ovarian stroma) – large coiled arteries (helicene arteries) give rise to straight cortical arterioles

these arterioles supply the follicles and lymphatics of the cortex

Histology – spindle-shaped cells (fibroblasts), fine collagen fibers, smooth muscle cells in ground substance

in cortex, follicles and corpus luteum (post-ovulatory follicle) are visible
may also see degenerated former corpus luteum (corpora albicans) and degenerate follicles (atresia)

Blood supply – ovarian artery (branch of aorta) and uterine artery – both enter at Hilum from the broad ligament

Ovarian Asymmetry – only one ovary is involved in the growth of antral follicles

active follicles appear enlarged and pink-red (due to hyperemia); inactive follicles appear small and white

Two Endocrine Structures are follicles and corpus luteum

Follicle – cellular sacs with endocrine activity where oocyte meiotic maturation (oogenesis) occurs

oogenesis – unequal division with formation of two polar bodies; two arrests of meiosis (primary oocyte prophase, secondary oocyte metaphase) – 2^nd meotic division completion depends on fertilization

follicular maturation occurs primarily via FSH, acting synergistically with estrogen and LH

recruitment – a group of follicles is stimulated by gonadotropins to grow in only one ovary

selection – during menstrual cycle, only one follicle of the group is selected to become the preovulatory follicle

"fail-safe" mechanism – cohort follicles will replace dominant follicle if it is removed

Developmental Events, Stages, and Histology

Primordial Germ Cells (oogonia)

week 6 – migration to ovarian cortex
multiply by mitosis

Primary Oocyte (4^th - 5^th month)

oogonia enlarge and assume potential for development into mature gamete

Primordial Follicle

arrest of 1^st meiotic division in prophase
primary cell encapsulated by a single layer of flattened follicular cells (non-growing)

Primary Follicle – oocyte is enlarged

zona pellucida – layer of glycoprotein and acid proteoglycans between oocyte and follicular cells(granulosa)

zona granulosa – follicular cells have multiplied to several layers (mitosis)

theca folliculi – organization of surrounding stromal cells separated from follicular cells by basement membrane

Secondary follicle (pre-antral)

follicular antrum – cavity within the zona granulosa in which follicular fluid accumulates

cumulus oophorus – thickened multilayered area of the granulosa – has endocrine function
Theca folliculi differentiate into:

theca interna – rounded cells, steroid secreting cells (estrogen, progesterone, intrafollicular FSH, inhibin F (FSH inhibitor))

theca externa – spindle shaped cells, no endocrine function

Antral Follicle (Mature or Graafian)

Follicular antrum enlarges, zona glomerulosa forms even layer around cell
1.5-2.5cm diameter

corona radiata – diminished cumulus oophorus around the oocyte

Control of Differentiation

Non-cyclic growth – independent of gonadotropins

primordial follicle – primary follicle

Cyclic Growth – dependent on gonadotropic surge from pituitary

FSH – binds to granulosa cells to stimulate mitosis

LH – binds thecal cells to initiate synthesis of androgen (estradiol produced via aromatase in granulosa cells)

primary Þ secondary follicle

Ý secretion of estrogen progressively inhibits release of FSH and promotes LH release (estrogen promotes proliferation of uterus in preparation for implantation)

estradiol – stimulates growth in granulosa cells of follicles

Antral Follicle

1^st meiotic division completed, 2^nd meiotic division commences

high levels of estrogen inhibit FSH release and promotes large LH release

Ovulation – release of egg

When the mature follicle ruptures, the ovum (consisting of the secondary oocyte, zona pellucida, and corona radiata) are expelled into the peritoneal cavity near the entrance to the uterine tube

Mechanism – not completely understood

occurs 24hrs after LH peak (not rapid release)

local Ý in collagenase Þ weakens follicular wall

theca externa has smooth muscle Þ contractile force

completion of 1^st meiotic division and formation of 1^st polar body occurs after LH surge

Corpus Luteum – collapsed dominant follicle

produces appropriate state for capacitation, fertilization, and implantation via progesterone and estrogen
maintained only if fertilization occurs
without fertilization, it degenerates and becomes Corpus Albican

Histological Changes

large cell in meiotic arrest (metaphase of 2^nd meiotic division); thick extracellular glycoprotein zona pellucida; cortical granules, Ý golgi memebranes and rough endoplasmic reticulum

Zona granulosa Þ granulosa lutein (yellow pigment of cytoplasm) cells Þ secrete progesterone – promotes exocrine secretion by glands in uterine endometrium

Theca Interna Þ theca lutein cells Þ secrete estrogen – maintains uterine lining

leutenizing hormone – requires LH binding to granulosa and lutein cells, inhibited by Ý progesterone.

Atresia – of the appoximately 400,000 oocytes, 99% will degenerate

Only the "selected" follicle will differentiate whereas the other follicles will degenerate (atresia)

atresia can strike a follicle at any stage of development. Occurs from prenatal life throughout reproductive life.

Signs of Atresia – loss of FSH,LH, Estradiol receptors, nuclear pyknosis, dissolution of granulosa cells, PMN’s

Estrogen ß atresia, testosterone Ý atresia (utilized for in vitro fertilization techniques)

Oviducts – a.k.a. fallopian tubes

Function – muscular tube under endocrine control which:

Transports the egg from the ovary to the uterus
Provides a suitable microenvironment for fertilization
May serve for implantation of zygote (tubal pregnancy)

Histological Layers

Terminal fimbriae (fingers)

Lining – ciliated and non-ciliated columnar epithelium covering lamina propria (non-ciliated are secretory)

Mucosa – blood vessels within strands of smooth muscle

Muscularis – inner spiral layer, outer longitudinal layer

Four regions from ovary to uterus – demonstrate cyclical mucosal alterations with endocrine control

(1) Infundibulum – tall mucosal folds, mainly ciliated columnar epithelium

(2) Ampulla – large lumen; Ý secretory cells; fusiform cells (decidual response), fertilization usually occurs here

(3) Isthmus – small lumen; Ý ratio of nonciliated/ciliated cells; thick muscular layers

(4) Pars interstitialis – small lumen; non-ciliated cells; traverses the uterine walls

regional variations ensure control of secretory cells, ciliary and muscular activity for optimal fertilization environment

Uterus

Histological layers:

(1) Mucosa (Endometrium) – simple columnar ciliated epithelium, tubular glands (secretory cells), decidual cells

secreted proteins create milieu for sperm capacitation and preimplantation blastocyst
secretory cells build up glycogen – diagnostic of postovulatory period

lamina propria – stromal cells (fibroblasts) with cyclic growth dependent on estradiol and progesterone
also present: inflammatory cells - immune system releases IgA; antibodies highest during luteal phase (C. luteum)

(2) Muscularis (myometrium) – smooth muscle (hypertrophies during prenancy), target for estrogen and progesterone

(3) Serosa (perimetrium)

Menstrual (uterine) Cycle – endometrium undergoes regular cyclical changes relative to ovarian secretions of estradiol and progesterone to offer an environment for implantation of a fertilized ovum

Endometrial Structure – two distinct compartments

(1) Upper transient functionalis – shed during cycle, becomes part of placenta

(2) Deep germinal basalis – permanent stem or progenitor cells, gives rise to functionalis

endometriosis: ectopic endometrial growth

Arterial supply – coiled (spiral) arteries; growth and differentiation dependent on estradiol and progesterone