Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 25The Gonads: Development & Function of the Reproductive System 423

The terms hypomenorrhea and menorrhagia refer to
scanty and abnormally profuse flow, respectively, during regu-
lar periods. Metrorrhagia is bleeding from the uterus between
periods, and oligomenorrhea is reduced frequency of periods.
Dysmenorrhea is painful menstruation. The severe menstrual
cramps that are common in young women quite often disap-
pear after the first pregnancy. Most of the symptoms of dys-
menorrhea are due to accumulation of prostaglandins in the
uterus, and symptomatic relief has been obtained by treatment
with inhibitors of prostaglandin synthesis.
Some women develop symptoms such as irritability, bloat-
ing, edema, decreased ability to concentrate, depression,
headache, and constipation during the last 7 to 10 d of their
menstrual cycles. These symptoms of the premenstrual syn-
drome (PMS) have been attributed to salt and water reten-
tion. However, it seems unlikely that this or any of the other
hormonal alterations that occur in the late luteal phase are
responsible because the time course and severity of the symp-
toms are not modified if the luteal phase is terminated early
and menstruation produced by administration of mifepris-
tone. The antidepressant fluoxetine (Prozac), which is a sero-
tonin reuptake inhibitor, and the benzodiazepine alprazolam
(Xanax) produce symptomatic relief, and so do GnRH-releas-
ing agonists in doses that suppress the pituitary–ovarian axis.
How these diverse clinical observations fit together to pro-
duce a picture of the pathophysiology of PMS is still unknown
(see Clinical Box 25–5).

PREGNANCY

Fertilization & Implantation

In humans, fertilization of the ovum by the sperm usually oc-
curs in the ampulla of the uterine tube. Fertilization involves

(1) chemoattraction of the sperm to the ovum by substances

produced by the ovum; (2) adherence to the zona pellucida,

the membranous structure surrounding the ovum; (3) pene-

tration of the zona pellucida and the acrosome reaction; and

(4) adherence of the sperm head to the cell membrane of the

ovum, with breakdown of the area of fusion and release of the

sperm nucleus into the cytoplasm of the ovum (Figure 25–33).

Millions of sperms are deposited in the vagina during inter-

course. Eventually, 50 to 100 sperms reach the ovum, and

many of them contact the zona pellucida. Sperms bind to a

sperm receptor in the zona, and this is followed by the acroso-

mal reaction, that is, the breakdown of the acrosome, the lyso-

some-like organelle on the head of the sperm (Figure 25–14).

Various enzymes are released, including the trypsin-like pro-

tease acrosin. Acrosin facilitates but is not required for the

penetration of the sperm through the zona pellucida. When

one sperm reaches the membrane of the ovum, fusion to the

ovum membrane is mediated by fertilin, a protein on the sur-

face of the sperm head that resembles the viral fusion proteins

that permit some viruses to attack cells. The fusion provides the

signal that initiates development. In addition, the fusion sets

off a reduction in the membrane potential of the ovum that

prevents polyspermy, the fertilization of the ovum by more

than one sperm. This transient potential change is followed by

a structural change in the zona pellucida that provides protec-

tion against polyspermy on a more long-term basis.

The developing embryo, now called a blastocyst, moves

down the tube into the uterus. This journey takes about 3 d,

during which the blastocyst reaches the 8- or 16-cell stage.

Once in contact with the endometrium, the blastocyst becomes

surrounded by an outer layer of syncytiotrophoblast, a multi-

nucleate mass with no discernible cell boundaries, and an inner

layer of cytotrophoblast made up of individual cells. The syn-

cytiotrophoblast erodes the endometrium, and the blastocyst

CLINICAL BOX 25–5

Genetic Defects Causing Reproductive

Abnormalities

A number of single-gene mutations cause reproductive ab-

normalities when they occur in women. Examples include

(1) Kallmann syndrome, which causes hypogonadotropic hy-

pogonadism; (2) GnRH resistance, FSH resistance, and LH re-

sistance, which are due to defects in the GnRH, FSH, or LH

receptors, respectively; and (3) aromatase deficiency, which

prevents the formation of estrogens. These are all caused by

loss-of-function mutations. An interesting gain-of-function

mutation causes the McCune–Albright syndrome, in which

Gsα becomes constitutively active in certain cells but not

others (mosaicism) because a somatic mutation after initial

cell division has occurred in the embryo. It is associated with

multiple endocrine abnormalities, including precocious pu-

berty and amenorrhea with galactorrhea.

FIGURE 25–33 Sequential events in fertilization in mammals.

Sperm are attracted to the ovum, bind to the zona pellucida, release

acrosomal enzymes, penetrate the zona pellucida, and fuse with the

membrane of the ovum, releasing the sperm nucleus into its cyto-

plasm. Current evidence indicates that the side, rather than the tip, of

the sperm head fuses with the egg cell membrane. (Modified from

Vacquier VD: Evolution of gamete recognition proteins. Science 1999;281:1995.)

Zona

pellucida

Egg cytoplasm

Egg cell membrane

Sperm

tail

Nucleus

Acrosome