The reproductive phenotype of the male aromatase knockout mouse

The process of spermatogenesis involves a coordinated series of developmental events to form a mature spermatozoon capable of fertilisation from an immature spermatogonium. These maturation steps occur within the seminiferous tubules of the testis, in close communication with the supportive Sertoli cells and surrounding interstitium, and then in the epididymal ducts. This process has been well characterised with respect to androgens and gonadotrophins. Oestrogens were also recognised to be synthesised in many of these reproductive structures. Although abnormal levels of oestrogens at various stages of development were shown to result in abnormalities in spermatogenesis, suggesting the test is was a possible oestrogenic site of action, the exact role of oestrogen remained unclear. A specific and direct role for oestrogen was not unreasonable given that both oestrogen receptors, predominantly ER~, and aromatase were localised in the testis. Through gene targeting technology, models have been designed to elucidate oestrogen action, with the significance of this 'female' hormone in the process of male fertility now beginning to be realised. The model described in these studies is the aromatase knockout (ArKO) mouse. The ArKO mouse lacks a functional aromatase cytochrome P450 enzyme, thus is unable to catalyse the conversion of C 19 steroids (androgens) to CI 8 steroids (oestrogens).