FIG. 2. Determinants of normal male and female sex differentiation in the human. In the presence of the testis determining factor (TDF) gene the undifferentiated gonad in the male undergoes testis determination. Sertoli cells develop and secrete Mullerian inhibiting substance (MIS) that promotes regression of Mullerian structures. Leydig cells in the testis produce testosterone (T) which acts locally to promote Wolffian duct development. By four months in the female, the male ducts have disappeared and the Mullerian ducts have fused to form the fallopian tubes, uterus and upper two-thirds of the vagina. In the male, the Mullerian ducts have regressed and testosterone from the ipsilateral testis has stimulated the Wolffian ducts to proliferate, forming the epididymides, vasa deferens, and seminal vesicles. Testosterone carried by the fetal circulation is converted locally to dihydrotestosterone which interacts with androgen receptors to promote masculinization of the external genitalia. The genital tubercle grows to form the penis. The urethral folds fuse and are incorporated to form the urethra while the labioscrotal folds fuse to form the scrotum. Later in gestation, the testes descend into the scrotum.