• spontaneous, cyclical ovulation at 25- to 35-day intervals continues

during almost 40 years between menarche and menopause

• 400 opportunities for pregnancy, which may occur with intercourse
on any of 1200 days—the day of ovulation and its two preceding days.
• placenta mediates a unique fetal–maternal communication system,
which creates a hormonal environment that initially maintains
pregnancy and eventually initiates events leading to parturition
• Predictable, regular, cyclical, and spontaneous ovulatory menstrual
cycles are regulated by complex interactions of the hypothalamic-
pituitary axis, ovaries, and genital tract.
• The average cycle duration is approximately 28 days, with a range of
25 to 32 days.
The Ovarian Cycle
• Follicular or Preovulatory Ovarian Phase
• Ovulation
• Luteal or Postovulatory Ovarian Phase
Follicular or Preovulatory Phase
• Ovary: 2 million oocytes (birth) and approximately 400,000 follicles
(puberty)
• Remaining follicles: depleted at a rate of approximately 1000 follicles/month
until age 35
• Only 400 follicles are normally released during female reproductive
life.
• >99.9% of follicles undergo atresia via apoptosis
Ovulation
• gonadotropin surge: 34 to 36 hours before ovum release from the
follicle
• from increasing estrogen secretion by preovulatory follicles
• relatively precise predictor of ovulation
• LH secretion peaks 10 to 12 hours before ovulation
• stimulates resumption of meiosis in the ovum and release of the first polar
body.
Luteal or Postovulatory Ovarian Phase
• luteinization: corpus luteum develops from the dominant or Graafian
follicle remains
• LH: corpus luteum maintenance
• The human corpus luteum is a transient endocrine organ that, in the
absence of pregnancy, will rapidly regress 9 to 11 days after ovulation
via apoptotic cell death.
• from decreased levels of circulating LH in the late luteal phase and decreased
LH sensitivity of luteal cells
Estrogen
• 17β-estradiol: is secreted by granulosa cells of the dominant follicle
and luteinized granulosa cells of the corpus luteum
• two classic nuclear hormone receptors: estrogen receptor α (ERα) and
β (ERβ)
Progesterone
• progesterone receptor type A (PR-A) and B (PR-B)
• enters cells by diffusion and in responsive tissues becomes associated
with progesterone receptors
The Endometrial Cycle
• Proliferative or Preovulatory Endometrial Phase
• Secretory or Postovulatory Endometrial Phase
• Menstruation
Proliferative Phase
Early Secretory Phase
Secretory Phase
• Estradiol action is decreased.
• rising progesterone levels >> glandular cell mitosis ceases with secretory
activity
• glandular expression of the type 2 isoform of 17β-hydroxysteroid
dehydrogenase >> estradiol to estrone
Late Secretory Phase
Menstruation
• Leukocyte infiltration: key to both endometrial extracellular matrix
breakdown and repair of the functionalis layer.
• “inflammatory tightrope”: ability of macrophages to assume
phenotypes that vary from proinflammatory and phagocytic to
immunosuppressive and reparative.
• Invading leukocytes secrete enzymes of the matrix metalloprotease
(MMP) family. These add to the proteases already produced by
endometrial stromal cells and effectively initiate matrix degradation.
• As tissue shedding is completed, microenvironment-regulated
changes in macrophage phenotype promote repair and resolution.
Menstruation
Anatomical Events
• endometrial regression >> severe spiral artery coiling >> inc resistance
to blood flow >> endometrial hypoxia
• Resultant stasis: primary cause of endometrial ischemia and tissue
degeneration.
• Vasoconstriction precedes menstruation and is the most striking and
constant event observed in the cycle.
• Intense spiral artery vasoconstriction: limits menstrual blood loss.
Prostaglandins
• Progesterone withdrawal >> inc expression of COX-2 (prostaglandin
synthase 2) >> prostaglandin synthesis
• Withdrawal >> dec expression of 15-hydroxyprostaglandin
dehydrogenase (PGDH) >> increased prostaglandin production by
endometrial stromal cells and increased prostaglandin receptor
density on blood vessels and surrounding cells.
• Dysmenorrhea: mediated by PGF 2α -induced spiral artery
vasoconstriction that causes the uppermost endometrial zones to
become hypoxic.
Menstrual blood
• Arterial
• rupture of a spiral arteriole >> hematoma >> distention and eventual
rupture of superficial endometrium >> fissures develop in the
adjacent functionalis layer >> sloughing off of blood and tissue
fragments >> endometrial bleeding
• Hemorrhage stops with arteriolar constriction and changes
accompanying partial tissue necrosis also serve to seal vessel tips.
Endometrium
• The endometrial surface is restored by growth of flanges, or collars,
that form the everted free ends of the endometrial glands.
• These flanges increase in diameter very rapidly, and epithelial continuity is
reestablished by fusion of the edges of these sheets of migrating cells.
Interval between menses
• The modal interval of menstruation is considered to be 28 days
Decidua
• specialized, highly modified endometrium of pregnancy.
• essential for hemochorial placentation
• Decidualization: transformation of secretory endometrium to decidua
• is dependent on estrogen and progesterone and factors secreted by the
implanting blastocyst.
Decidua
• early pregnancy: the decidua begins to thicken (depth of 5 to 10 mm).
• With magnification, furrows and numerous small openings, representing the
mouths of uterine glands, can be detected.
• late pregnancy: the decidua becomes thinner.
• pressure exerted by the expanding uterine contents
Decidua
• 3 layers of decidua parietalis and basalis:
• zona compacta: surface or compact zone
• zona spongiosa: a middle portion or spongy zone, with remnants of
glands and numerous small blood vessels
• zona basalis: basal zone
• remains after delivery and gives rise to new endometrium
• zona functionalis= compacta + spongiosa
Decidual Reaction
• completed only with blastocyst implantation
• Predecidual changes: during the midluteal phase in endometrial stromal
cells adjacent to the spiral arteries and arterioles. Thereafter, they spread
in waves throughout the uterine endometrium and then from the
implantation site.
• endometrial stromal cells: enlarge to form polygonal or round decidual
cells
• Nuclei: round and vesicular
• Cytoplasm: clear, slightly basophilic, and surrounded by a translucent
membrane. Each mature decidual cell becomes surrounded by a
pericellular membrane.
Decidual Reaction
• endometrial stromal cells: enlarge to form polygonal or round
decidual cells
• Nuclei: round and vesicular
• Cytoplasm: clear, slightly basophilic, and surrounded by a translucent
membrane
• pericellular membrane: surrounds each mature decidual cell
Decidual Blood Supply
• BS to the decidua capsularis is lost as the embryo-fetus grows.
• BS to the decidua parietalis through spiral arteries persists and retain
a smooth-muscle wall and endothelium >> responsive to vasoactive
agents.
Decidual Blood Supply
• The spiral arterial system supplying the decidua basalis are invaded by
cytotrophoblasts. The vessel walls in the basalis are destroyed. Only a
shell without smooth muscle or endothelial cells remains >> not
responsive to vasoactive agents.
• fetal chorionic vessels (transport blood between the placenta and the
fetus): contain smooth muscle >> respond to vasoactive agents.
Decidual Histology
• Early: zona spongiosa consists of large distended glands, often
exhibiting marked hyperplasia and separated by minimal stroma.
• glands are lined by typical cylindrical uterine epithelium with abundant
secretory activity that contributes to blastocyst nourishment
• Late: epithelium gradually becomes cuboidal or even flattened >>
degenerates and sloughs to a greater extent into the gland lumens >>
glandular elements largely disappear
Decidual Histology
• The decidua basalis contributes to formation of the placental basal
plate.
• differs histologically from the decidua parietalis
• spongy zone of the decidua basalis: mainly of arteries and widely dilated
veins, and by term, glands have virtually disappeared
• decidua basalis is invaded by many interstitial trophoblast cells and
trophoblastic giant cells
Decidual Histology
• Nitabuch layer: is a zone of fibrinoid degeneration in which invading
trophoblasts meet the decidua basalis.
• Rohr stria: more superficial, but inconsistent, deposition of fibrin at
the bottom of the intervillous space and surrounding the anchoring
villi.
• Early: a striking abundance of large, granular lymphocytes termed
decidual natural killer (NK) cells
• important role in trophoblast invasion and vasculogenesis.
Decidual Prolactin
• prolactin levels in amnionic fluid are extraordinarily high and may
reach 10,000 ng/ mL at 20 to 24 weeks’ gestation
• fetal serum levels of 350 ng/mL and maternal serum levels of 150 to
200 ng/mL
• paracrine function between maternal and fetal tissues
Decidual Prolactin
• may serve in transmembrane solute and water transport and in
amnionic fluid volume maintenance.
• may act in regulating immunological functions during pregnancy.
• may play a role in angiogenesis regulation during implantation.
Fertilization and Implantation
Zygote
• After fertilization
• Diploid cell with 46 Chromosomes
Morula
• a solid mulberry-like ball of cells
• morula enters the uterine cavity
about 3 days after fertilization.
Blastocyst
• 4 to 5 days after fertilization
• measures approximately 0.155 mm in diameter
Blastocyst Implantation
• 6 or 7 days after fertilization
• 3 phases:
• Apposition
• Adhesion – integrin
• Invasion