Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 25

The Gonads: Development & Function of the Reproductive System 395

both male and female primordial genital ducts (Figure 25–4).
In a normal female fetus, the müllerian duct system then devel-
ops into uterine tubes (oviducts) and a uterus. In the normal
male fetus, the wolffian duct system on each side develops into
the epididymis and vas deferens. The external genitalia are sim-
ilarly bipotential until the eighth week (Figure 25–5). Thereaf-
ter, the urogenital slit disappears and male genitalia form, or,
alternatively, it remains open and female genitalia form.
When the embryo has functional testes, male internal and
external genitalia develop. The Leydig cells of the fetal testis
secrete testosterone, and the Sertoli cells secrete
müllerian
inhibiting substance
(
MIS;
also called müllerian regression
factor, or MRF). MIS is a 536-amino-acid homodimer that is a
member of the transforming growth factor
β
(TGF-
β
) super-
family of growth factors, which includes inhibins and activins.

In their effects on the internal as opposed to the external geni-

talia, MIS and testosterone act unilaterally. MIS causes regres-

sion of the müllerian ducts by apoptosis on the side on which it

is secreted, and testosterone fosters the development of the vas

deferens and related structures from the wolffian ducts. The

testosterone metabolite dihydrotestosterone induces the forma-

tion of male external genitalia and male secondary sex charac-

teristics (Figure 25–6).

MIS continues to be secreted by the Sertoli cells, and it

reaches mean values of 48 ng/mL in plasma in 1- to 2-year-old

boys. Thereafter, it declines to low levels by the time of

puberty and persists at low but detectable levels throughout

life. In girls, MIS is produced by granulosa cells in small folli-

cles in the ovaries, but plasma levels are very low or undetect-

able until puberty. Thereafter, plasma MIS is about the same

FIGURE 25–5
Differentiation of male and female external genitalia from indifferent primordial structures in the embryo.

INDIFFERENT STAGE

MALE FEMALE

Glans penis

Clitoris

Urethral

meatus

Urethral meatus

Labia

minora

Vaginal

orifice

Labia

majora

Scrotum

Raphe

Anus

Phallus

Genital swelling Urethral slit

Tail

Glans

Genital tubercle

Urogenital slit

Urethral fold

Labioscrotal

swelling

Anus

SEVENTH TO EIGHTH WEEK

TWELFTH WEEK