The influence of estrogen on the developing male marsupial

The genes and hormones involved in gonadal differentiation are highly conserved between eutherians and marsupials, although the timing of the developmental events differs. In marsupials, the testis develops seminiferous cords two days after birth, and the ovaries are not distinguishable until around eight days after birth. Differentiation of the internal genitalia is controlled in marsupials, as in eutherians, by testicular testosterone and Müllerian inhibiting substance, but differentiation of the scrotum in males and mammary primordia in females is hormone-independent. Since the young are easily accessible in the pouch, it is possible to administer gonadal hormones during the period of sexual differentiation. In both Australian and South American marsupials, estradiol treatment of neonatal males can induce male-to-female gonadal sex reversal. The testicular transformations range from partial suppression of seminiferous tubule development to the development of a morphologically normal ovary depending on the stage that treatment starts. The sex-reversed testes have a clearly defined cortex and medulla, and there are significantly fewer germ cells. The germ cells are surrounded by follicle-like cells and are in the early stages of meiosis, as is normal for XX germ cells in ovaries. In normal males, germ cells only enter meiosis at the onset of puberty. As in eutherians, estrogen treatment of neonatal male marsupials prevents regression of the Müllerian ducts, which are hypertrophic. Neonatal estradiol exposure also causes hypertrophy of the prostate and urogenital sinus. Estradiol treatment also inhibits transabdominal testicular descent and many animals develop inguinal hernias. The ability of estradiol to cause testis-to-ovary sex reversal in marsupials provides a new way of studying the interactions between genes and hormones in testicular differentiation.