CHAPTER
Endocrine Metabolism V:
Reproductive System
The sex of an individual is the outcome of genetic de-
terminants (genotypic sex) and of hormonal effects that
confer structural features characteristic of a given sex
(phenotypic sex). Both genetic and hormonal determinants
normally operate only at two phases of life: during fetal de-
velopment and at puberty. Genotypic sex is either homoga-
metic (XX) or heterogametic (XY). In humans and other
mammals, the homogametic (XX) pairing programs ovar-
ian development and oocyte formation (oogenesis), while
the heterogametic (XY) pairing leads to testicular devel-
opment and spermatogenesis. In both genotypes, the em-
bryonal gonads develop from the epithelium and stroma of
the urogenital ridge, a thickening of the coelomic (ventro-
medial) aspect of the mesonephros that emerges at about
the second or third week of pregnancy. Both the epithe-
lium and stroma of the urogenital ridge are derived from
the intermediate mesoderm of the embryo; however, in-
vading this structure at about week 4 are primordial germ
cells from the yolk sac, which take residence in association
with the epithelial cells of the developing gonad and repli-
cate. During the germ cell invasion, the epithelial cells of
the gonads undergo proliferation and begin entering the
stromal spaces as cord-like projections, called “primary
sex cords.” Until about week
6
, the gonads are undiffer-
entiated and uncommitted; that is, the structure has the
potential to develop into either ovaries or testes.
A list of expanded acronyms appears as Appendix VIII.
The fetal gonads develop in parallel with the Wolffian
(mesonephric) duct and the Mullerian (paramesonephric)
duct, both of which are positioned bilaterally to the gonads
within the urogenital ridge. The Wolffian duct begins form-
ing from about week 4, starting at the mesonephros and
terminating caudally at the cloaca. The Mullerian duct be-
gins forming from about week
6
and merges caudally with
the urogenital sinus. The Wolffian duct is the primordium
of the male reproductive tract, whereas the Mullerian duct
is the primordium of the female reproductive tract. Until
about week
8
, both ducts are present and undifferenti-
ated. In the absence of a Y chromosome, a gene on the X
chromosome directs the development of fetal gonads into
ovaries. This critical sex-determining gene located on the
X chromosome is known as the
DAX-1
gene. Subsequent
to the action of this gene, the Mullerian ducts develop into
a female genital tract and the Wolffian duct regresses.
In the presence of a Y-chromosome, the
SRY
gene (sex-
determining region of the Y-chromosome) antagonizes the
action of the
DAX-1
gene (the
SRY
gene was previously
known as testis-determining factor, TDF). Mutations in the
SRY
gene can result in an XY female with gonadal dys-
genesis. Testis differentiation may also require the par-
ticipation of a gene located on chromosome 17 (
SOX9
gene). The precise interaction between
SOX9
and
SRY
in
gonadal development is not yet understood; however, both
genes code for DNA-binding proteins. Mutations in the
SOX9
gene can result in sex reversal in XY individuals
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