**1.3 The role of androgens in male reproductive tract development**

Male reproductive tract development is a dynamic process requiring the interaction of many factors and hormones. One of the major factors essential for the development of the male internal and external male reproductive tract are the androgens, testosterone and dihydrotestosterone (DHT) (Phillips & Tanphaichitr, 2008). Androgens are produced by the testes during fetal and neonatal development and are essential for the maintenance of the Wolffian duct that differentiates into the epididymis, vas deferens and the seminal vesicles. The masculinization of these reproductive structures is mediated by testosterone. The masculinization of the external genitalia and prostate is largely mediated by DHT which is a more potent metabolite of testosterone and is produced by the action of the enzyme 5αreductase. The central role of androgens in driving these developmental processes illustrates why chemicals that can interfere with the synthesis or action of androgens can have deleterious consequences for the developing male genital tract. Administration of the antiandrogen, flutamide (an androgen receptor antagonist), during male reproductive tract development resulted in abnormalities in the formation of the external genitalia hypospadias and cryptorchidism; internally, agenesis of the epididymis, vas deferens and prostate (Mylchreest et al., 2000). Within the testis, degeneration of the seminiferous epithelium and Leydig cell hyperplasia were common (although this may be a consequence of the cryptorchidism rather than an anti-androgenic effect). The male pups also displayed retained thoracic nipples and a reduced anogenital distance (feminised) which are both indicative of reduced androgen action in fetal life (Mylchreest et al., 2000). In summary, both testosterone- and DHT-mediated male reproductive tract development is impaired by flutamide when administered over the period of reproductive tract differentiation.
