Chapter 22 The Female Reproductive System - each becomes surrounded by flattened support cells called follicular

- Paired ovaries and oviducts (or uterine tubes) + uterus + vagina + cells to form a non-growing follicular cell.
external genitalia
- It produces the female gametes (oocytes) “Ovarian Reserve”
- The ovaries produce steroidal sex hormones - At birth there about 680, 000 follicles
- 460, 000 remain at puberty, others are lost through atresia (a
Menarche degenerative process) which only ends with menopause.
- when the first menses occurs - Only 450 oocytes are liberated from ovaries by ovulation, all others
- the reproductive system undergoes monthly changes in structure degenerate through atresia.
and function. - Reproductive life of a woman is 30-35 years
Menopause
- variably timed period where the cyclic changes become irregular
and eventually disappear.
Postmenopausal Period
- the reproductive organs slowly involute
- The mammary glands (although not included here) also undergo
changes directly connected here.
_________________________________________________
OVARIES
Shape: Almond-shaped
Covering: Simple cuboidal epithelium which is also called the
“Surface (or germinal) epithelium”
This overlies the
Tunica Albuginea (dense connective tissue)

Cortex
- a region with a stroma of highly cellular connective tissue and many
ovarian follicles varying greatly in size after menarche.
Medulla
- the most internal part of the ovary
Tissue Type: Loose Connective tissue + blood vessels

_______________________________________________________

Ovarian Follicles
- consists of an oocyte
surrounded by one or more
layers or epithelial cells within a
basal lamina.

a] PRIMORDIAL FOLLICLES
- Follicles that are formed
during fetal life
- consist of a primary oocyte
enveloped by a single layer of
the flattened follicular cells.
Location: Occurs in the
______________________________________________________
superficial ovarian cortex
Early Development of the Ovary
Primordial Germ cells - The oocyte in here is spherical
with a large nucleus containing
- In the first month of embryonic life, these migrate from the yolk sac
chromosomes in the first
to the gonadal primordia.
- As the ovaries develop, these germ cells undergo synchronized meiotic prophase.
mitotic divisions with incomplete cytokinesis, producing a few
million interconnected oogonia. _____________________________________________________
- This ceases at 11-12 weeks gestation in humans and the clustered
oogonia enter the long prophase of a first meiotic division. Follicular Growth and Development
- Most of these cells undergo apoptotic cell death, but others - Beginning in puberty, with the release of FSH from the pituitary, a
complete synapsis and genetic recombination and then arrest small group of primordial follicles each month begins a process of
without progressing to later stages of meiosis. follicular growth.
PRIMARY OOCYTES - Involves growth of the oocyte, proliferation, and changes in the
- Cells in meiotic arrest follicular cells, as well as proliferation and differentiation of the
stromal fibroblasts around each follicle.
- Prompted by FSH, an oocyte grows most rapidly during the first part
of follicular development. and the granulosa cells reorganize themselves around a larger cavity
OOCYTE DIFFERENTIATION: called the antrum, producing follicles now called…
> Growth of the cell and nuclear enlargement
> Mitochondria becoming more numerous and uniformly distributed. d] SECONDARY (or ANTRAL) FOLLICLES
> RER becoming much more extensive and Golgi complexes enlarging - as the antrum develops, the granulosa cells around the oocyte form
and moving peripherally. a small hillock (Cumulus Oophorus) which protrude into the antrum.
> Formation of specialized secretory granules called cortical granules Corona Radiata
containing various proteases (these lie just inside the oocyte’s plasma - The tightly adhering granulosa cells immediately surrounding the
membrane and undergo exocytosis early in fertilization). zona pellucida make up this.
- Accompanies the oocyte when it leaves the ovary at ovulation.
b] UNILAMINAR PRIMARY FOLLICLE
- Follicular cells undergo mitosis and form a simple cuboidal e] MATURE (or GRAAFIAN) FOLLICLE
epithelium around the growing oocyte. - after the 17th century reproductive biologist Regnier de Graaf
- Its single large antrum rapidly accumulates more follicular fluid and
c] MULTILAMINAR PRIMARY FOLLICLE expands.
- The follicular cells continue to proliferate, forming a stratified - It forms a bulge at the ovary surface.
follicular epithelium, the granulosa, in which the cells communicate - The granulosa layer becomes thinner at this stage because its cells
through gap junctions. do not multiply in proportion to the growth of the antrum.
- Follicular cells are now called granulosa cells - This has thick thecal layers and normally develops from a primordial
- Still avascular and surrounded by a basement membrane. follicle over a period of about 90 days.
_______________________________________________________
Zona Pellucida Follicular Atresia
- Between the oocyte and the first layer of granulosa cells of the - Most ovarian follicles undergo atresia, in which follicular cells and
growing primary follicle, extracellular material accumulates as this. oocytes undergo apoptosis and removal by phagocytic cells. Follicles
- Contains four glycoproteins secreted by the oocyte at any stage of development, including nearly mature follicles, may
ZP3 and ZP4 become atretic.
- zona pellucida components - It involves detachment of the apoptotic granulosa cells, autolysis of
- important sperm receptors, binding specific proteins on the sperm the oocyte, and collapse of the zona pellucida.
surface and inducing acrosomal activation. - Macrophages invade the degenerating follicle and phagocytose the
Note: Filopodia of granulosa cells and Microvilli of the oocyte apoptotic material and other debris.
penetrate the zona pellucida, allowing communication between - During a woman’s fourth decade, menopause begins when atresia
these cells via gap junctions. and ovulation have reduced the ovarian reserve to fewer than about
1000 follicles.
Follicular Theca - During the menstrual cycle, one follicle becomes dominant and
- stromal cells immediately outside each growing primary follicle develops farther than the others.
differentiate to form this.
- vascularized Dominant Follicle
- differentiates as two tissues around the follicle: - usually reaches the most developed stage of follicular growth and
undergoes ovulation, while the other primary and antral follicles
Theca Interna Theca Externa undergo atresia.
Well-vascularized endocrine tissue with More fibrous with - Although their oocytes are never directly used, the large growing
steroid-producing cells secreting fibroblasts and follicles each month produces much estrogen before becoming
androstenedione. This precursor smooth muscle atretic.
molecule diffuses into the follicle merges gradually - This estrogen stimulates preparation of the reproductive tract to
through the basement membrane, and with the surrounding transport and sustain the embryo if the oocyte from the dominant
in the granulosa cells, the enzyme stroma follicle is fertilized.
aromatase converts it to estradiol, an _______________________________________________________
FSH-dependent function. This estrogen Ovulation and its Hormonal Regulation
returns to the thecae and stroma OVULATION
around the follicle, enters capillaries, - hormone-stimulated process by which the oocyte is released from
and is distributed throughout the body, the ovary.
inducing the changes in puberty. - normally occurs midway through the menstrual cycle, around the
As the primary follicles grow, they move deeper in the ovarian cortex. 14th day of a 28-day cycle.
Within such follicles, small spaces appear between the granulosa - In the hours before ovulation, the mature dominant follicle bulging
layers as the cells secrete… against the tunica albuginea develops a whitish or translucent
ischemic area, the stigma, in which the tissue compaction has
Follicular fluid (or liquor folliculi)
blocked blood flow.
- contains large GAG hyaluronic acid, growth factors, plasminogen,
- In humans, usually only one oocyte is liberated during each cycle,
fibrinogen, the anticoagulant heparan sulfate proteoglycan, and high
but sometimes either no oocyte or two or more simultaneous
concentrations of steroids (progesterone, androstenedione, and
oocytes may be expelled.
estrogens) with binding proteins.
- Just before the ovulation, the oocyte completes the first meiotic
- this fluid accumulates, the spaces enlarge and gradually coalesce,
division which began and arrested in prophase during fetal life.
  Meiosis I is complete by the primary oocyte, yielding a
secondary oocyte and the first polar body that degenerates.
 Granulosa cells are stimulated to produce more follicular
fluid containing prostaglandins, proteoglycans, and
proteases that remove the surrounding blood-follicle
barrier. The granulosa cells in the cumulus oophorus-oocyte
complex mainly release hyaluronan1
1
Hyaluronan
- increases the fluid viscosity and swells to greatly increase
the extracellular volume within the complex, loosening its
outer cells, and dissociating it from the follicle wall.
 Ballooning at the stigma, the ovarian wall weakens as
activated by plasminogen (plasmin) from broken capillaries
degrades collagen in the tunica albuginea and surface
epithelium.
 Smooth muscle contractions begin in the theca externa,
triggered by prostaglandins diffusing from follicular fluid.

The increasing pressure with the follicle and weakening of the wall
lead to rupture of the ovarian surface at the stigma. The oocyte and
its surrounding corona radiata, along with follicular fluid, are expelled
- The chromosomes are equally divided between the two daughter by the local smooth muscle contractions.
cells, but one of these retains almost all of the cytoplasm.
The ovulated secondary oocyte adheres loosely to the ovary surface
SECONDARY OOCYTE in the viscous follicular fluid and is drawn into the opening of the
- the one that retains almost all the cytoplasm. uterine tube where fertilization may occur. If not fertilized within 24
FIRST POLAR BODY hours, the secondary oocyte begins to degenerate. Cells of the
- very small non-viable cell containing a nucleus and a minimal ovulated follicle that remain in the ovary re-differentiate under the
amount of cytoplasm. influence of LH and give rise to the CORPUS LUTEUM.
- Immediately after expulsion of the first polar body, the nucleus of ________________________________________________________
the oocyte begins the second meiotic division but arrests at Corpus Luteum
metaphase and never completes meiosis unless fertilization occurs. - After ovulation, the granulosa cells and theca interna of the
ovulated follicle reorganize to form a larger temporary endocrine
Follicular development depends on FSH from pituitary gland, the corpus luteum, in the ovarian cortex.
gonadotropins, whose secretion is stimulated by gonadotropin-
releasing hormone (GnRH) from the hypothalamus. - Ovulation is followed by the collapse and folding of the granulosa
and thecal layers of the follicle’s wall, and blood from disrupted
Negative feedback of estrogen and progesterone on the capillaries accumulates as a clot in the former antrum.
hypothalamus and anterior pituitary is reinforced by inhibin (a
polypeptide hormone which is also produced by granulosa and luteal - The granulosa is not invaded by capillaries. Cells of both the
cells) granulosa and theca interna change histologically and functionally
under the influence of LH, thus becoming specialized for more
In the days preceding ovulation, the dominant follicle secretes higher extensive production of progesterone in addition to estrogens.
levels of estrogen that stimulate more rapid pulsatile release of GnRH
from the hypothalamus. GRANULOSA LUTEIN CELLS
- Granulosa cells increase greatly in size without dividing and
The increased level of GnRH causes a surge of LH release from the eventually comprise about 80% of the corpus luteum.
pituitary gland that rapidly triggers a sequence of major events in and - have lost many features of protein-secreting cells to expand their
around the dominant follicle: role in aromatase conversion of androstenedione into estradiol.

THECA LUTEIN CELLS

- The former theca interna forms the rest of the corpus luteum as
this.
- half the size of granulosa lutein cells
- typically aggregated in the folds of the wall of the corpus luteum,
which becomes well vascularized.

- LH causes these cells to produce large amounts of progesterone and

androstenedione.
- The short term of the corpus luteum depends on whether a
pregnancy occurs.
- The ovulatory LH surge causes the corpus luteum to secrete
progesterone for 10-12 days
- Without further LH stimulation and in the absence of pregnancy,
both major cell types of the corpus luteum cease steroid production
and undergo apoptosis, with regression of the tissue.

Menstruation
- A consequence of the decreased secretion of progesterone
- the shedding of part of the uterine mucosa.
- Estrogen produced by the active corpus luteum inhibits FSH release
from the pituitary.
- However, after the corpus luteum degenerates, the blood steroid
concentration decreases and FSH secretion increases again,
stimulating the growth of another group of follicles and beginning the
next menstrual cycle.
Corpus Luteum of Menstruation
- The corpus luteum that persists for part of only one menstrual cycle
- Remnants from its regression are phagocytosed by macrophages,
after which fibroblasts invade the area and produce a scar of dense
connective tissue called a corpus albicans.

If pregnancy occurs, the uterine mucosa must not be allowed to

undergo menstruation because the embryo would be lost.
To prevent the drop in circulating progesterone, trophoblast cells of Lining Epithelium: Simple Columnar Epithelium (with two cell types)
the implanted embryo produce a glycoprotein hormone called
Human Chorionic Gonadotropin (hCG) Ciliated cells Secretory peg cells
- has targets and activity similar to that of LH ciliary movements sweep fluid non-ciliated and often darker
- Maintains and promotes further growth of the corpus luteum, toward the uterus staining, often with an apical
stimulating secretion of progesterone to maintain the uterine bulge into the lumen, which
mucosa. secrete glycoproteins of a
Corpus Luteum of Pregnancy nutritive mucus film that covers
- This becomes very large the epithelium.
- maintained by hCG for 4-5 months, by which time the placenta itself Lamina Propria: Loose Connective tissue
produces progesterone (and estrogens) at levels adequate to
maintain the uterine mucosa. Triggered primarily by estrogens, the cilia elongate and both cell
- It then degenerates and is replaced by a large corpus albicans. types undergo hypertrophy during the follicular growth phase of the
________________________________________________________ ovarian cycle and undergo atrophy with loss of cilia during the late
UTERINE TUBES (or OVIDUCTS) luteal phase.
- The paired uterine tubes or oviducts, supported by ligaments and
mesenteries, allow considerable motility. At the time of ovulation, mucosal hypertrophy and increase local
- Each opens into the peritoneal cavity near the ovary, with regions in blood flow have enlarged and moved the uterine tube. The fringed
the following sequence: infundibulum lies very close to the ovary and the fimbriae partially
surround that organ. This favors the transport of the ovulated
 The infundibulum, a funnel-shaped opening fringed with secondary oocyte into the tube. Promoted by sweeping muscular
finger-like extensions called fimbriae next to the ovary contractions of the fimbriae and ciliary activity, the oocyte enters the
 The ampulla, the longest and expanded region where infundibulum and moves to the ampulla. The secretion covering the
fertilization normally occurs. mucosa has nutritive and protective functions for both the oocyte
 The isthmus, a narrower portion nearer the uterus and the sperm, including capacitation factors, that activate sperm
 The uterine or intramural part, which passes through the and make those cells able to fertilize oocyte.
wall of the uterus and opens into the interior of this organ. ________________________________________________________
Major Events of Fertilization
The wall of the oviduct consists of a folded mucosa, a thick, well- FERTILIZATION
defined muscularis with interwoven circular (or spiral) and - The union of the female and male gametes
longitudinal layers of smooth muscle, and a thin serosa covered by - occurs in the ampulla of a uterine tube, a site usually reached by
visceral peritoneum with mesothelium. only a few hundred sperms
- Only sperm that have undergone capacitation in the female
The numerous branching, longitudinal folds of the mucosa are most reproductive tract are capable of fertilization, a process with the
prominent in the ampulla, which in cross section resembles a following steps:
labyrinth.
These mucosal folds become smaller in the regions closer to the  Upon contact with cells of the corona radiata, sperm
uterus and are absent in the intramural portion of the tube. undergo the acrosomal reaction in which hyaluronidase is
released by exocytosis at multiple locations around the
sperm head. This allows sperm to move ore easily to the
zona pellucida.
  Specific proteins on the sperm surface bind the receptors muscle cells, which strengthens the uterine wall.
ZP3 and ZP4, activating the protease acrosin on the - This well-developed uterine myometrium contracts very forcefully
acrosomal membrane to degrade the zona pellucida locally. during parturition to expel the infant from the uterus.
 The first sperm penetrating the zona pellucida fuses with the - After pregnancy, uterine smooth muscle cells shrink and many
oocyte plasmalemma and triggers Ca2+ release from vesicles, undergo apoptosis, with removal of unneeded collagen, and the
which induces exocytosis of proteases from the cortical uterus returns almost to its pregnancy size.
granules. This cortical reaction quickly spreads like a wave
across the entire surface of the oocyte, with the proteases Endometrium
converting the zone pellucida to the impenetrable - Its lamina propria (or stroma) contains primarily non-bundled type
perivitelline barrier that constitutes a permanent block to III collagen fibers with abundant fibroblasts and ground substance.
polyspermy.
 The nucleus of the secondary oocyte immediately completes Lining Epithelium: Simple columnar epithelium with ciliated and
meiosis II, producing a second polar body and the female secretory cells (the latter lines the tubular uterine glands)
pronucleus of the haploid ovum. The haploid nucleus if the
Two Concentric Zones of the Endometrium
single penetrating sperm head undergoes de-condensation,
Basal Layer Functional Layer
becoming the male pronucleus. Fusion of the two pronuclei
yields the new diploid cell, the zygote. Adjacent to the myometrium Superficial
Has a more highly cellular Has a spongier lamina propria,
Cell division occurs while the embryo is transported by contractions lamina propria richer in ground substance
of the oviduct muscularis and ciliary movements to the uterus, which Contains the deep basal ends of Includes most of the length of
takes about 5 days. This transport occurs in women with immotile the uterine glands the glands and the surface
ciliary syndrome, indicating a more important role for muscle epithelium.
contractions in moving the embryo.
________________________________________________________
UTERUS The functional layer
Shape: Pear-shaped with thick muscular walls undergoes profound
Body changes during the
- Its largest part menstrual cycles, but the
- entered by the left and right uterine tubes. basal layer remains
Fundus relatively unchanged.
- the curved, superior area between the tubes The blood vessels supplying
the endometrium have
- The uterus narrows in the isthmus and ends in a lower cylindrical special significance in the
structure, the cervix. periodic sloughing of the
functional layer during
Cervical Canal menses.
- The lumen of the cervix
- has constricted openings at each end: Arcuate arteries in the
middle layers of the
Internal os External os myometrium send two sets
Opens to the main uterine lumen Opens to the vagina of smaller arteries into the
endometrium:
Three Major Layers of the Uterine Wall: Straight arteries Spiral arteries
Supply only the Long, progesterone-sensitive, which extend
Perimetrium Myometrium Endometrium basal layer farther and bring blood throughout the
Outer CT layer, A thick tunic of A mucosa lined by simple functional layer.
continuous with highly columnar epithelium. These branch with numerous arterioles
the ligaments, vascularized supplying a rich, superficial capillary bed
which is smooth muscle. The thickness and that includes many dilated, thin walled
adventitial in structure of the vascular lacunae drained by venules.
some areas, but endometrium is
________________________________________________________
largely a serosa influenced cyclically by the
MENSTRUAL CYCLE
covered by shifting levels of ovarian
- Estrogens and progesterone control growth and differentiation of
mesothelium. hormones even more than
epithelial cells and associated connective tissue.
the mucosa of the uterine
- Even before birth, these cells are influenced by circulating maternal
tubes.
estrogen and progesterone that reach the fetus though the placenta.
Myometrium - After menopause diminished synthesis of these hormones results in
- the thickest tunic of the uterus a general involution of tissues in the reproductive tract.
- shows bundles of smooth muscle fibers separated by connective - The duration of the menstrual cycle averages 28 days
tissue containing venous plexuses and lymphatics. - a woman is fertile only during the years when she is having
- During pregnancy, this goes through a period of extensive growth menstrual cycles.
involving both hyperplasia (increasing the number of smooth muscle
cells), cell hypertrophy, and increased collagen production by the
 At the end of the proliferative phase, the endometrium is 2-3 mm
thick.

Secretory (or Luteal) Phase

- starts as a result of the progesterone secreted by the corpus luteum
- Progesterone stimulates epithelial cells of the uterine glands that
formed during the proliferative phase and these cells being to secrete
and accumulate glycogen, dilating the glandular lumens, and causing
the glands to become coiled.
- Includes thin-walled blood-filled lacunae.
- The endometrium reaches its maximum thickness

- If fertilization occurred during the day after ovulation, the embryo

has been transported to the uterus by about 5 days later and now
attaches to the uterine epithelium when the endometrial thickness
and secretory activity are optimal for embryonic implantation and
nutrition.

- The major nutrient source for the embryo before and during
implantation is the uterine secretion.
- From puberty until menopause (45-50 y/o) pituitary gonadotropins - Progesterone inhibits strong contractions of the myometrium that
produce cyclic changes in ovarian hormone levels, which cause the might interfere with embryo implantation.
endometrium to undergo cyclic modifications during the menstrual
cycle Menstrual Phase
- Day 1 of the menstrual cycle is usually taken as the day when - When fertilization of the oocyte and embryonic implantation do not
menstrual bleeding appears. The menstrual discharge consists of occur, the corpus luteum regresses and circulating levels of
degenerating endometrium mixed with blood from its ruptured progesterone and estrogens begin to decrease 8-10 days after
microvasculature. ovulation, causing the onset of menstruation.

Menstrual Phase Proliferative Phase Secretory Phase - The drop-off in progesterone produces:
lasts 3-4 days on - the next phase Begins at ovulation (1) spasms of muscle contraction in the small spiral arteries of the
average - is of variable length, and lasts about 14 functional layer, interrupting normal blood flow
8-10 days on average days. (2) increased synthesis by arterial cells of prostaglandins, which
The cyclic structural changes occur gradually and the activities produce strong vasoconstriction and local hypoxia. Cells undergoing
characterizing these phases overlap to some extent. hypoxic injury release cytokines that increase vascular permeability
and immigration of leukocytes. The leukocytes release collagenase
and several other matric metalloproteinases (MMPs) that degrade
basement membranes and other ECM components.

- Major portions of the functional layer, including the surface

epithelium, most of each glands, the stroma and blood-filled lacunae,
detach from the endometrium and slough away as the menstrual
flow or menses.

- Arterial constriction normally limits blood loss during menstruation,

Proliferative (or Follicular or Estrogenic) Phase but some blood does emerge from the open ends of venules.
- After the menstrual phase, the uterine mucosa is relatively thin.
- its beginning coincides with the rapid growth of a small group of - At the end of the menstrual phases, the endometrium is reduced to
ovarian follicles growing as vesicular follicles. a thin layer and is ready to begin a new cycle as its cells begin dividing
- With development of their theca interna, these follicles actively to reconstitute the mucosa.
secrete estrogen and increase its plasma concentrations. ________________________________________________________
EMBRYONIC IMPLANTATION, DECIDUA, & THE PLACENTA
Estrogen act on endometrium, inducing regeneration of the - The zygote produced by fertilization undergoes mitotic cleaves as it
functional layer lost during menstruation. Cells in the basal ends of is moved toward the uterus, with its cells called blastomeres in a
glands proliferate, migrate, and form the new epithelial covering over compact aggregate called the morula.
the surface exposed during menstruation.
- No growth occurs during the period of cell cleavage, with
During the proliferative phase, the endometrial lining is a simple blastomeres becoming smaller at each division, and the morula is
columnar surface epithelium and the uterine glands are relatively about the same size as the oocyte at fertilization.
straight tubules with narrow, empty lumens.
- About 5 days after fertilization, the embryo reaches the uterine
Spiral arteries lengthen as the functional layer is re-established and cavity by which time blastomeres have moved to form a central
grows and extensive microvasculature forms near the surface of the cavity in the morula and the embryo enters the blastocyst stage of
functional layer. development.
 The blastomeres then Placenta
arrange themselves as - site of exchange
a peripheral layer for nutrients,
called the trophoblast wastes, O2, and
around the cavity while CO2 between the
a few cells just inside mother and the
this layer make up the fetus
embryoblast or inner - contains tissue
cell mass. The from both
blastocyst remains in individuals
the lumen of the - endocrine gland
uterus for about 2 - produces hCG, a
days, immersed in the lactogen, relaxin,
endometrial glands’ various growth
secretion on the factors, and
mucosa. estrogen and
progesterone.
Chorion
- embryonic part
Implantation (or nidation) - derived from trophoblast and the maternal part is from the decidua
- involves attachment of the blastocyst to the surface epithelial cells basalis.
of the endometrium and its proteolytic through this epithelium into
the underlying stroma. - Exchange occurs between embryonic blood in chorionic villi outside
- last about 3 days the embryo and maternal blood in lacunae of the decidua basalis.
- cells of the trophoblast drive the events of implantation, during - Chorionic villi of the developing placenta go through three stages:
which time cells of the embryoblast rearrange around two new
cavities, the amnion and the yolk sac.  Primary Villi appear 2 days after implantation as simple
cords of proliferating cytotrophoblast cells covered by
- Where the cells lining these cavities make contact, the bilaminar syncytiotrophoblast extend into lacunae containing
embryonic disc develops with its epiblast layer continuous with the maternal blood.
amnion and its hypoblast layer continuous with the yolk sac.  Secondary Villi begin to form on about the 15th day of
embryonic development as the primary villi are invaded by
All parts of the embryo develop from this early embryonic disc. The extraembryonic mesenchyme.
yolk sac and amnion form extra-embryonic structures, but only the  Tertiary Villi develop within a few more days as
latter persists throughout pregnancy. mesenchyme in the secondary villi differentiates to form
capillary loops continuous with the embryonic circulatory
The trophoblast differentiates during implantation into the following:
system.
Cytotrophoblast Syncytiotrophoblast
A layer of mitotically active cells A more superficial, non-mitotic
Chorionic villi
immediately around the amnion mass of multinucleated cytoplasm - provide surface area for metabolite exchange.
and yolk sac that invades the surrounding - Exchange of gases, nutrients, and wastes occurs between fetal
stroma. blood in capillaries and maternal blood (from the decidua) bathing
By about the 9th day after ovulation, the embryo is totally implanted the villi and the capillary endothelium.
in the endometrium and derives nutrients primarily from blood ____________________________________________________
there. CERVIX
Cytotrophoblast cells - synthesize anti-inflammatory cytokines to - It is the lower, cylindrical part of the uterus (but different
prevent an adverse uterine reaction to the implanted embryo and histologically)
these are supplemented later by various embryonic factors that Endocervical Mucosa: Simple columnar epithelium on a thick
produce local immune tolerance for the embryo throughout the lamina propria
pregnancy. - It also has many cervical glands (large, branched, mucus-secreting)
Decidua - It lacks spiral arteries, does not change its 2-3mm thickness during
- The endometrial stroma undergoes histologic changes in the period the ovarian cycle, and is not shed during menstruation.
following implantation.
- Fibroblasts become enlarged, polygonal, more active in protein Exocervical Mucosa
synthesis, and are now called decidual cells. - Covers the cervical region which projects slightly into the upper
- The whole endometrium is now called the decidua. vagina and is around the external os.
Epithelium: Non-keratinized Stratified Squamous Epithelium
Three areas of Decidua
Decidua Basalis Decidua Capsularis Decidua Parietalis Transformation Zone
Area between the Region between the On the side of the - The junction between the squamous epithelium and the mucus-
implanted embryo embryo and uterine uterus away from the secreting columnar epithelium of the endocervix occurs here.
and myometrium lumen that thins as embryo - area just outside the external os that shifts slightly with the cyclical
the embryo gets larger changes in uterine size.
Intraepithelial neoplasia Vestibule Labia Minora Labia Majora Clitoris
- Periodic exposure of the squamous-columnar junction to the vaginal A space Paired folds of Paired, Erectile
environment can stimulate reprogramming of epithelial stem cells whose wall skin lacking homologous, structure like
and can lead to this. includes the hair follicles histologically the penis with
tubuloacinar but with many similar to the paired
Cervical mucus vestibular sebaceous skin of corpora
- Under the influence of progesterone, its consistency changes glands. glands. scrotum. cavernosa.
cyclically and plays a significant role in fertilization and early The mucosa of these structures abundantly supplied with sensory
pregnancy. nerves and tactile receptors is important in physiology of sexual
arousal.
Ovulation Luteal phase Pregnancy
________________________________________________________
mucous secretion is mucus is more The cervical glands
MAMMARY GLANDS (MG)
abundant and viscous and hinders proliferate and
watery, facilitating the passage of secrete highly - the mammary glands of
sperm movements sperm. viscous mucus that the breasts develop
into the uterus. forms a plug in the embryologically as
cervical canal. invaginations of surface
ECTODERM along two
Cervix’s deeper wall TX type: Dense Connective Tissue with much ventral lines, from the
less smooth muscle that the rest of the uterus. axillae to the groin.
The cervix becomes relatively rigid during pregnancy - Each mammary gland
Thus, it helps retain the fetus in the uterus. consists of 15-25 lobes of
the compound
Cervical Effacement tubuloalveolar type.
- Before parturition, this occurs wherein its connective tissue - The function of this is
undergoes extensive remodeling and significant collagen removal, to secrete nutritive milk for
mediated in part by macrophages. newborns.
- As a result, the cervix softens, the cervical canal dilates, and birth - Each lobe, separated from the others by DENSE CT with much
occurs more easily. ADIPOSE TX, is a separate gland with its own excretory LACTIFEROUS
________________________________________________________ DUCT.
VAGINA
- Its wall lacks glands and consists of a mucosa, a muscular layer, and Lactiferous Duct
an adventitia. Lining Epithelium: Simple Cuboidal Epithelium with many
myoepithelial cells
Epithelium of Mucosa: Stratified Squamous Epithelium - Emerge independently in the nipple, which has 15-25 pore-like
- The mucosa contains many lymphocytes and neutrophils. openings (each about 0.5 mm diameter)
- Stimulated by estrogens, the epithelial cells synthesize and
accumulate glycogen. **Histologic structure of MG varies with sex, age, physiologic status.
- When the cells desquamate, bacteria metabolize glycogen to lactic BREAST DEVELOPMENT DURING PUBERTY
acid, causing a relatively low pH in the vagina. - Before puberty, the mammary glands in both sexes are compose
- This helps provide a protecting against pathogenic microorganisms. only of lactiferous sinuses near the nipple, with very small, branching
ducts emerging from the sinuses.
Lamina Propria: Rich in elastic fibers, with numerous papillae
projecting into the overlying epithelium. Estrogen
- higher levels of this cause the breasts to grow (in girls undergoing
Cervical Glands puberty) as a result of adipocyte accumulation and elongation of the
- these produce mucus in the vagina duct system.
Glands at the Vaginal Vestibule and the paired greater vestibular Pre-menstrual Phase
glands (of Bartholin) provide lubricating mucus during sexual arousal. - CT of the breast becomes edematous, making them slightly larger.
- These are homologous to male bulbourethral glands.
Terminal Duct Lobular Units (or Lobules)
Muscular Layer: Circular bundles (next to the mucosa) Lining Epithelium: Simple Cuboidal Epithelium with many
Thicker Longitudinal bundles (near adventitia) myoepithelial cells
In non-pregnant women, each MG lobe consists of many lobules.
Adventitia: Dense Connective tissue rich in elastic fibers.
- Each of these has several small, branching ducts, but the attached
- This makes the vaginal wall strong and elastic
secretory units are small and rudimentary.
- This outer layer also contains an extensive venous plexus,
lymphatics, and nerves. Lactiferous Sinuses
________________________________________________________ Lining Epithelium: Stratified Cuboidal Epithelium
EXTERNAL GENITALIA (or VULVA)
Epithelium: Stratified Squamous Epithelium ** For Lactiferous and Terminal Ducts
Sparse fibers of smooth muscle also encircle the larger ducts.
The duct system is embedded in loose, areolar CT, and a denser, less They eventually undergo apocrine secretion wherein the
cellular CT separates the lobes. droplets become enveloped with a portion of the apical cell
membrane.
Areola
- skin surrounding and covering the nipple Milk contains 4g or 5 g of total fat per deciliter.
- contains sebaceous glands and abundant sensory nerves  Lactose
- it is continuous with the mucosa of the lactiferous sinuses. - major carbohydrate and energy source in milk
- Contains more melanin that the skin - It is synthesized in the Golgi apparatus and secreted with
- Darkens further during pregnancy. lactalbumin.
Connective Tissue: Rich in Smooth muscle fibers that run parallel to - It is also responsible for generating the osmotic gradient
the lactiferous sinuses and produce nipple erection when they that draws water and Ca2+ into the alveolar lumen.
contract.
Human milk contains over 7g of lactose per deciliter
BREASTS DURING PREGNANCY & LACTATION
- MG grows during pregnancy as a result of the synergistic action of Throughout lactation, secretion of proteins, membrane bound lipid
several hormones, mainly estrogen, progesterone, prolactin, and the droplets, lactose, iron, and calcium is ongoing, with the products
placental lactogen. accumulating as milk in the lumens of the duct system.
- These cause cell proliferation in secretory alveoli (spherical) at the
ends of the intralobular ducts POSTLACTATIONAL REGRESSION IN THE MAMMARY GLANDS
WEANING
Epithelium of the Alveoli: Cuboidal Epithelium with stellate - When breastfeeding is stopped
myoepithelial cells between the secretory cells and the basal lamina - Most alveoli that developed during pregnancy and lactation
degenerate.
- While the alveoli and duct system grow and develop during - Epithelial cells undergo apoptosis, autophagy, or sloughing, with
pregnancy in preparation for lactation, the stroma becomes less dead cells and debris removed by macrophages.
prominent. - The duct system of the gland returns to its general inactive state
- The loose CT within lobules is infiltrated by lymphocytes and plasma appearance.
cells, the latter becoming more numerous late in pregnancy.
- After menopause, alveoli and ducts of the MG are reduced further
Colostrum in size and there is loss of fibroblasts, collagen, and elastic fibers in
- Accumulation of this dilates the glandular alveoli and ducts late in
the stroma.
pregnancy.
- It is a fluid rich in proteins and contains leukocytes, which is
produced under the influence of prolactin.

- Immunoglobulin A (IgA) antibodies are synthesized abundantly by

PLASMA CELLS and transferred into colostrum, from which passive
acquired immunity is conferred on the breast-fed newborn.

- Following parturition, the alveoli of mammary glands start active

milk production (LACTATION), stimulated by prolactin from the
anterior pituitary.

- Epithelial cells of the alveoli enlarge and activate various process

involve in lactation:

 Large amounts of proteins are synthesized, packaged into

secretory vesicles, and undergo merocrine secretion into
the lumen.

Human milk contains about 1g protein per deciliter,

including aggregated caseins (44% of the total protein), as
well as soluble β-lactoglobulin and α-lactalbumin, all of
which area a source of amino acids by the infant.

Less abundant proteins in milk include many factors that

assist digestion like lactoferrin (with antimicrobial activity),
and other mitogenic growth factors important for gut
development in the newborn.
 Lipid droplets form initially from short-chain fatty acids
synthesized in the epithelial cells and grow by accretion of
longer fatty acids and cholesterol originating from the diet
or fat stores.