The masculinization programming window

Abstract

Sexual differentiation is a tightly regulated series of events which transform the indifferent gonads and genitalia into sex-specific structures. This is driven by hormones produced by the fetal testes, primarily testosterone (T). However, masculinization of each structure does not occur synchronously and, until recently, it was presumed that androgens also control this masculinization over a broad period of fetal life, coincident with the period of fetal T production. However, a common fetal masculinization programming window (MPW) has been identified in male and female rodent models in which androgens must act to masculinize all components of the reproductive tract and allow their later complete development. Impaired androgen action only within this MPW can induce cryptorchidism and hypospadias. This MPW is likely to occur between 8-14 weeks' gestation in humans. Studies in transgenic mice have begun to investigate some of the underlying mechanisms involved. Anogenital distance is predictive of the incidence of disorders, such as azoospermia, hypospadias and cryptorchidism, and could provide a noninvasive, lifelong indicator of androgen action within this MPW, useful in clinical assessment of patients with disorders of sexual development. In addition, several diagnostic characteristics of the external genitalia are also useful in investigating this MPW.