Endocrinology of the Fetal Testis

Abstract

The human fetus, already at a very early stage in its development, is hormonally active, with the testis and adrenal gland being major contributors. Following sex determination at around weeks 5–6, the somatic cells of the testis begin to differentiate into hormone-producing Sertoli and Leydig cells. The latter cells share similar origins to the steroidogenic cells of the adrenal cortex and fetal zones which at this stage of human development are located close to the testis. This changes following testis descent to the inguinal region caused by Leydig cell production of androgens and INSL3. In the first half of pregnancy, fetal hormones act more as paracrine systems diffusing locally within the fetus and amniotic fluid; consequently understanding fetal steroidogenesis at this stage requires knowledge of both testis and adrenal metabolism. Much of fetal testis develop-ment is governed and orchestrated by feedforward and feedback processes, combining with irreversible effects, such as the involution of the Mullerian ducts, the development of the Wolffian system, and testis descent. These pro-cesses and the timing of hormone and receptor expression are what lead to the high precision that results in the extremely low frequency of nongenetic disorders of sex development. This is now being challenged by in utero low-level exposure to a range of anthropogenic chemicals which appear capable of disrupting normal development.