Oestrogen at the neonatal stage is critical for the reproductive ability of male mice as revealed by supplementation with 17 beta-oestradiol to aromatase gene (Cyp19) knockout mice

Aromatase P450 (CYP19) is an enzyme responsible for the conversion of andro gens to oestrogens. We generated CYP19 knockout (ArKO) mice by targeted dis ruption of Cyp19 and studied the role of oestrogens in male reproductive ab ility. Approximately 85% of ArKO males were unable to sin offspring. Howeve r, no obvious difference was found in testicular and epididymal weights, nu mbers of sperm in the epididymis or the ability of sperm to fertilize eggs in vitro between wild-type and ArKO males. An examination of mating behavio ur demonstrated that ArKO males showed an impairment in mounting behaviour against sexually mature females. The inability of more than 90% of ArKO mal es to sire offspring was reversed by repeated subcutaneous injections of 17 beta -oestradiol when initiated on the day of birth. The effects of 17 bet a -oestradiol on reproduction were concentration dependent and evident when supplementation was initiated on day 7, but not on day 15 after birth. The se findings suggest that oestrogens acting during neonatal life are require d for normal mating behaviour in adulthood.