Reproduction
603
An easy method exists for determining whether a per-
son’s cells contain two X chromosomes, the typical female
pattern. When two X chromosomes are present, only one
functions, and the nonfunctional X chromosome condenses to
form a nuclear mass termed the
sex chromatin (Barr body),
which is readily observable with a light microscope. Scrapings
from the cheek mucosa or white blood cells are convenient
sources of cells to be examined. The single X chromosome in
male cells rarely condenses to form sex chromatin.
A more exacting technique for determining sex chromo-
some composition employs tissue culture visualization of all
the chromosomes—a
karyotype.
This technique is used to
identify a group of genetic sex abnormalities characterized by
such unusual chromosomal combinations such as XXX, XXY,
and XO (only one sex chromosome). The end result of such
combinations is usually the failure of normal anatomical and
functional sexual development.
Sex Differentiation
The multiple processes involved in the development of the
reproductive system in the fetus are collectively called
sex
differentiation.
It is not surprising that people with atypi-
cal chromosomal combinations can manifest atypical sexual
development. However, careful study has also revealed indi-
viduals with normal chromosomal combinations but abnormal
sexual appearance and function (
phenotype
). In these people,
sex differentiation has been atypical, and their phenotype may
not correspond with their genotype—that is, the presence of
XX or XY chromosomes.
It will be important to bear in mind during the follow-
ing description one essential generalization: the genes directly
determine only whether the individual will have testes or ova-
ries. The rest of sex differentiation depends upon the presence
or absence of substances produced by the genetically deter-
mined gonads, in particular, the testes.
Differentiation of the Gonads
The male and female gonads derive embryologically from the
same site—an area called the urogenital ridge. Until the sixth
week of uterine life, primordial gonads are undifferentiated. In
the genetic male, the testes begin to develop during the sev-
enth week. A gene on the Y chromosome (the
SRY
gene,
for
s
ex-determining
r
egion of the
Y
chromosome) is expressed at
this time in the urogenital ridge cells and triggers this devel-
opment. In the absence of a Y chromosome and, consequently,
the
SRY
gene, testes do not develop. Instead, ovaries begin to
develop in the same area at about 11 weeks.
By what mechanism does the
SRY
gene induce the for-
mation of the testes? This gene codes for a protein, SRY, which
sets into motion a sequence of gene activations ultimately
leading to the formation of testes from the various embryonic
cells in the urogenital ridge.
There is an unusual and important fact concerning the
behavior of the X and Y chromosomes during meiosis. As
described earlier in this chapter, during meiosis, homologous
chromosomes come together, line up point for point, and then
exchange fragments with each other, resulting in an exchange of
genes (recombination) on these chromosomes. Such crossing-
over involving the Y and X genes, however, could allow the
SRY
gene—the male-determining gene—to get into the
female’s genome. To prevent this, by mechanisms still not
understood, the Y and X chromosomes do not undergo recom-
bination (except at the very tips, where the
SRY
gene is not
located and the Y chromosome has the same genes as the X).
Differentiation of Internal
and External Genitalia
The internal duct system and external genitalia of the fetus
are capable of developing into either sexual phenotype. Before
the functioning of the fetal gonads, the primitive reproductive
tract includes a double genital duct system comprised of the
Wolffi
an ducts
and
Müllerian ducts,
and a common open-
ing for the genital ducts and urinary system to the outside.
Normally, most of the reproductive tract develops from only
one of these duct systems. In the male, the Wolffi
an ducts per-
sist and the Müllerian ducts regress, whereas in the female, the
opposite happens. The external genitalia in the two genders and
the outer part of the vagina do not develop from these duct sys-
tems, however, but from other structures at the body surface.
Which of the two duct systems and types of external
genitalia develops depends on the presence or absence of fetal
testes. These testes secrete (1) testosterone from the Leydig
cells and (2) protein hormone called
Müllerian-inhibiting
substance (MIS)
from the Sertoli cells (
Figure 17–3a
).
SRY protein induces the expression of the gene for MIS; MIS
then causes the degeneration of the Müllerian duct system.
Simultaneously, testosterone causes the Wolffi
an ducts to dif-
ferentiate into the epididymis, vas deferens, ejaculatory duct,
and seminal vesicles. Externally and somewhat later, under
the infl uence primarily of
dihydrotestosterone (DHT)
pro-
duced from testosterone in target tissue, a penis forms, and
the tissue near it fuses to form the scrotum. The testes will
ultimately descend into the scrotum, stimulated to do so by
testosterone. Failure of the testes to descend is called
crypt-
orchidism
and is common in infants with decreased andro-
gen secretion. Because sperm production requires about 2°C
lower temperature than normal core body temperature, sperm
production is usually decreased in cryptorchidism. Treatments
include hormone therapy and surgical approaches to move the
testes into the scrotum.
In contrast, the female fetus, not having testes (because
of the absence of the
SRY
gene), does not secrete testosterone
and MIS. In the absence of MIS, the Müllerian system does
not degenerate but rather develops into fallopian tubes and
a uterus. In the absence of testosterone, the Wolffi
an ducts
degenerate, and a vagina and female external genitalia develop
from the structures at the body surface (
Figure 17–3b
).
Ovaries, though present in the female fetus, do not play a role
in these developmental processes. In other words, female devel-
opment will occur automatically unless stopped from doing so
by the presence of factors released from functioning testes.
There are various conditions in which normal sex differen-
tiation does not occur. For example, in
androgen insensitivity
syndrome
(also called
testicular feminization
), the genotype
is XY and testes are present, but the phenotype (external
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