CHAPTER 25
The Gonads: Development & Function of the Reproductive System 397arm of their father’s Y chromosome was transposed to their
father’s X chromosome during meiosis and they received that
X chromosome along with their mother’s. Similarly, deletion
of the small portion of the Y chromosome containing SRY
produces females with the XY karyotype.
Hormonal Abnormalities
Development of the male external genitalia occurs normally in
genetic males in response to androgen secreted by the embry-
onic testes, but male genital development may also occur in ge-
netic females exposed to androgens from some other source
during the 8th to the 13th weeks of gestation. The syndrome
that results is
female pseudohermaphroditism.
A pseudoher-
maphrodite is an individual with the genetic constitution and
gonads of one sex and the genitalia of the other. After the 13th
week, the genitalia are fully formed, but exposure to androgens
can cause hypertrophy of the clitoris. Female pseudohermaph-
roditism may be due to congenital virilizing adrenal hyperpla-
sia (see Chapter 22), or it may be caused by androgens
administered to the mother. Conversely, one cause of the de-
velopment of female external genitalia in genetic males
(male
pseudohermaphroditism)
is defective testicular development.
Because the testes also secrete MIS, genetic males with defec-
tive testes have female internal genitalia.
Another cause of male pseudohermaphroditism is
andro-
gen resistance,
in which, as a result of various congenital
abnormalities, male hormones cannot exert their full effects
on the tissues. One form of androgen resistance is a
5
α- reductase deficiency,
in which the enzyme responsible for the
formation of dihydrotestosterone, the active form of testoster-
one, is decreased. The consequences of thisdeficiency are dis-
cussed in the section on the male reproductive system. Other
forms of androgen resistance are due to various mutations in
the androgen receptor gene, and the resulting defects in recep-
tor function range from minor to severe. Mild defects cause
TABLE 25–1
Classification of the major disorders of
sex differentiation in humans.*
Chromosomal disorders
Gonadal dysgenesis (XO and variants)
“Superfemales” (XXX)
Seminiferous tubule dysgenesis (XXY and variants)
True hermaphroditism
Developmental disorders
Female pseudohermaphroditism
Congenital virilizing adrenal hyperplasia of fetus
Maternal androgen excess
Virilizing ovarian tumor
Iatrogenic: Treatment with androgens or certain synthetic
progestational drugs
Male pseudohermaphroditism
Androgen resistance
Defective testicular development
Congenital 17
α
-hydroxylase deficiency
Congenital adrenal hyperplasia due to blockade of pregnenolone
formation
Various nonhormonal anomalies*Many of these syndromes can have great variation in degree and, consequently, in
manifestations.
CLINICAL BOX 25–1
Chromosomal Abnormalities
An established defect in gametogenesis is
nondisjunction,
a phenomenon in which a pair of chromosomes fail to sepa-
rate, so that both go to one of the daughter cells during mei-
osis. Four of the abnormal zygotes that can form as a result
of nondisjunction of one of the X chromosomes during oo-
genesis are shown in Figure 25–7. In individuals with the XO
chromosomal pattern, the gonads are rudimentary or ab-
sent, so that female external genitalia develop, stature is
short, other congenital abnormalities are often present, and
no sexual maturation occurs at puberty. This syndrome is
called
gonadal dysgenesis
or, alternatively,
ovarian agene-
sis
or
Turner syndrome.
Individuals with the XXY pattern,
the most common sex chromosome disorder, have the geni-
talia of a normal male. Testosterone secretion at puberty is
often great enough for the development of male characteris-
tics, however, the seminiferous tubules are abnormal, and
the incidence of mental retardation is higher than normal.
This syndrome is known as
seminiferous tubule dysgene-
sis
or
Klinefelter syndrome.
The XXX (“superfemale”) pat-
tern is second in frequency only to the XXY pattern and may
be even more common in the general population, since it
does not seem to be associated with any characteristic ab-
normalities. The YO combination is probably lethal.
Nondisjunction of chromosome 21 produces
trisomy
21,
the chromosomal abnormality associated with
Down
syndrome
(mongolism). The additional chromosome 21 is
normal, so Down syndrome is a pure case of gene excess
causing abnormalities.
Many other chromosomal abnormalities occur as well as
numerous diseases due to defects in single genes. These
conditions are generally diagnosed in utero by analysis of
fetal cells in a sample of amniotic fluid collected by inserting
a needle through the abdominal wall
(amniocentesis)
or,
earlier in pregnancy, by examining fetal cells obtained by a
needle biopsy of chorionic villi
(chorionic villus sampling).