II.  Fertilization
-occurs within the oviduct
A.  Developmental changes in ejaculated sperm
-capacitation--changes occur in female reproductive tract which allow the acrosome reaction and further ability to fertilize to occur
-acrosome reaction-fusion of inner and outer acrosome membranes in sperm head, making zona-penetrating enzymes available
B.  Barriers to sperm penetration of zona pellucida
-must navigate cervical mucus
-must swim up the female tract
-must navigate the expanded cumulus cells
-penetrate the zona pellucida
C.  Sperm penetration of zona and fusion to perivitelline membrane
1.  Consequences of sperm penetration and fusion to perivitelline (or plasma membrane)
a. release of cortical granules which make the zona impenetrable by further sperm (block to polyspermy)
b. egg activation (completion of meiosis and release of second polar body)
D. Formation of Male pronucleus
1.  sperm head swells and separates from tail
2.  fusion of male and female pronuclei
3.  completion of fertilization and formation of zygote

III.  Embryo Development
1. egg divides by mitosis, although the total volume of the embryo does not change significantly until after implantation
2.  morula stage
-after several divisions (1-2-4-8-16), the embryo is a solid ball of cells or morula (berry) consisting of 16-32 cells
3.  blastocyst stage
-embryos entering the uterus are at the blastocyst stage
-the first stage of development at which cells are no longer totipotent but have begun to differentiate
-2 cell types form, the inner cell mass which will form the fetus and the trophoblast which will form the fetal placenta
-blastocysts “hatch” out of the zona pellucida and implant into the endometrium of the uterus

IV.  Implantation & Placentation
1.  invasion of the embryo requires breakdown of maternal tissue at the site of implantation.  This causes changes in the endometrium which cause it to differentiate into decidual tissue.
2.  Development of the placenta
a.  trophoblastic cords from the fetus become the placental villi which are filled with fetal capillaries
b.  Uterine arteries branch to form spiral arteries which end in maternal blood sinuses which surround the fetal placental villi.
c.  exhange of gases and nutrients such as glucose occur either by simple or facilitated diffusion between the fetal capillaries in the villi and the surrounding blood in the maternal blood sinuses.  In a healthy, intact placenta, there is no actual mixing of the blood!
d.  Diabetes of pregnancy
-some elevation of maternal blood glucose may be desirable to make glucose available to the fetus; however true hyperglycemia is not desirable
-may be due to hormone placental lactogen (aka chorionic somatomammotrophin) which causes partial insulin resistance

V.  Endocrinology of Pregnancy
A.  hCG production
1.  hCG is human chorionic gonadotropin, a hormone with very high homology to LH
-binds to LH receptors and activates them
-acts on luteal LH receptors and acts to maintain progesterone production by the corpus luteum
2.  Without hCG, the corpus luteum has a limited lifespan.  It is programmed to self-destruct after about 14 days.  When the corpus luteum regresses, menstruation ensues.  When the conceptus produces adequate hCG, the corpus luteum does not regress, and there is no menstruation.

B.  Progesterone production
-necessary to maintain uterus in quiescent state and maintain pregnancy
1.  First trimester
-depends on hCG to stimulate corpus luteum for progesterone production
2.  Second and third trimesters
-switch to a placental source of progesterone
-the placenta has the steroidogenic enzymes necessary to convert cholesterol from the mother’s blood into progesterone
-hCG declines
3.  Time of switch from luteal to placental progesterone production coincides with a high incidence of miscarriage

C.  Estrogen production
-the placenta produces great amounts of estradiol, estrone and estriol (but primarily estriol), but it requires androgen precursors produced by the fetal adrenal
-androgens diffuse out of the fetal adrenal and into the placenta where the rate limiting enzyme for estrogen production is located (aromatase)

D.  P:E ratio (progesterone to estrogen) (not price to earnings ratio as in stock market lingo)
-Near term, progesterone production by placenta decreases while estrogen production increases
-probably important in allowing uterine contractions to occur, although probably does not initiate uterine contractions
(see below relationships between estrogen, progesterone, prostaglandins and oxytocin for further enlightenment)

E.  Placental lactogen
-placental hormone that may be involved in partial insulin resistance in mother
-may be important in lactation
-acts through prolactin receptor
-molecule is similar to both prolactin and growth hormone
-may be involved in tissue growth during pregnancy (breast, uterus, external genitalia, etc)

F.  Relaxin
- produced by CL
-may be involved in relaxation of pubic ligaments?
-may be involved in cervical softening
-may be involved in nipple growth/development

VI.  Parturition
-key hormones involved in myometrial contractions are oxytocin and to a lesser extent prostaglandin(s)

A.  oxytocin
-posterior pituitary hormone
-released in response to stimuli such as increased intrauterine stretching and pressure
-acts on smooth muscles to initiate contraction
-oxytocin can stimulate release of prostaglandins
-plasma oxytocin concentrations increase near term
-uterine oxytocin receptor numbers increase near term

B.  Estrogens
-increase near term
-act to increase oxytocin and oxytocin receptors
-increase prostaglandin synthesis

C.  Progesterone
-decreases near term
-inhibits oxytocin and oxytocin receptor numbers
-declining progesterone and increasing estrogens act together to produce lots of oxytocin and its receptor

D.  Prostaglandins
-can be released when tissue is stretched
-stimulate uterine contractions
-involved in thinning of cervix

E.  Positive Feedback loop at term
-increased pressure and stretching in uterus due to increased size of fetus and shift in position

leads to

-release of oxytocin and prostaglandins in response to increased pressure (also favored by shift in P:E ratio

leads to

-uterine contractions

leads to

-further release of oxytocin and prostaglandins

leads to

-further uterine contractions

A. Anatomy of the breast
-alveoli
-lobules
-ducts
-myoepithelial cells are smooth muscle cells surrounding alveoli

B.  Breast Development
1.  Role of Estrogens
-fat deposition
-nipple growth
-duct growth
2.  Role of progesterone
-growth of alveolie and lobules
-alveolar secretory activity

C.  Milk production
1.  prolactin
-anterior pituitary hormone
-important hormone involved in milk synthesis, essential for secretory cell function and differentiation of breasts near term
-increases near term
-estrogen increases prolactin secretion and the number of prolactin receptors in breast tissue
-progesterone inhibits prolactin receptors
-suckling is a potent stimulus for prolactin release
2.  other hormones which are also needed for milk production
-cortisol
-growth hormone
-PTH
-insulin

D.  Milk ejection
-milk is stored within the lumen of the alveoli and must be ejected or “let down” during nursing
-oxytocin acts on the myoepithelial cells to cause them to contract, squeezing milk out into ducts and out through openings in the nipple
-oxytocin is released in response to the suckling stimulus in a neuroendocrine reflex arc

E.  Lactational anovulation
-prolactin suppresses gonadotropins
-due to highly variable patterns of nursing and inherent human variability, breast-feeding alone is not recommended as an adequate contraceptive method