Step 3: Gonadal Differentiation

The important event in gonadal differentiation is the commitment of the gonadal ridge to become either an ovary or a testis.

a. In males, the gonadal ridge develops into testes as a result of a product from a gene located on the Y chromosome. This product has been termed the "testis determining factor" or "sex determining region of the Y chromosome" (SRY).

b. In females, the absence of SRY, due to the absence of a Y chromosome, permits the expression of other genes which will trigger the gonadal ridge to develop into ovaries.

Step 4: Differentiation of the Internal Ducts and External Genitalia

The next step in sex differentiation depends upon the formation of two important hormones: the secretion of Mullerian (female) Inhibiting Substance (MIS) and the secretion of androgens.

If testes are developing normally, then Sertoli cells of the developing testes produce MIS which inhibits the growth of the female Mullerian ducts (the uterus and fallopian tubes) which are present in all fetuses early in development. Additionally, the Leydig cells of the testes start secreting androgens. Androgens are hormones that produce growth effects on the male Wolffian ducts (the epididymis, vas deferens, seminal vesicles) which are also present in all fetuses early in development.

Unlike the testes, the ovaries do not produce androgens. As a result, the Wolffian ducts fail to grow and consequently disappear in fetuses with ovarian development. In addition, the ovaries do not produce MIS at the appropriate time, and as a consequence, the Mullerian (female) ducts can develop.

In other words, two products of the developing testes are needed for normal male development. First, MIS must be secreted to inhibit female duct growth and androgens must be secreted to enhance male duct growth. In contrast, a female fetus with no developing testes will produce neither MIS nor androgens, and hence female ducts will develop and male ducts will disappear.

External Genitalia

In the female, absence of androgens permits the external genitalia to remain feminine: the genital tubercle becomes the clitoris, the genital swellings become the labia majora and the genital folds become the labia minora.

In the male, fetal androgens from the testes masculinize the external genitalia. The genital tubercle grows to become the penis and the genital swellings fuse to form the scrotum. The following diagrams illustrate each of these processes.