The effects of a single developmentally entrained pulse of testosterone in female neonatal mice on reproductive and metabolic functions in adult life

Early postnatal exposures to sex steroids have been well recognized to modulate predisposition to diseases of adulthood. There is a complex interplay between timing, duration and dose of endocrine exposures through environmental or dietary sources that may alter the sensitivity of target tissues to the exogenous stimuli. In this study, we determined the metabolic and reproductive programming effects of a single developmentally entrained pulse of testosterone (T) given to female mice in early postnatal period. CD-1 female mice pups were injected with either 5-g of T enanthate (TE) or vehicle (control[CON]group) within24hours after birthandfollowed to adult age.Atotal of66%of T-treated miceexhibited irregular cycling, anovulatory phenotype,andsignificantly higher ovarian weightsthan vehicle-treated mice. Longitudinal nuclear magnetic resonance measurements revealed that TE group hadgreaterbodyweight,whole-bodylean,andfatmassthantheCONgroup.Adiposetissue cellularity analysis in TE group revealed a trend toward higher size and number than their littermate CONs. The brown adipose tissue of TE mice exhibited white fat infiltration with down-regulation of several markers, including uncoupling protein 1 (UCP-1), cell death-inducingDNAfragmentation factor,--subunitlike effector A, bone morphogenetic protein 7 as well as brown adipose tissue differentiation-related transcription regulators. T-injected mice were also more insulin resistant than CON mice. These reproductive and metabolic reprogramming effects were not observed in animals exposed to TE at 3 and 6 weeks of age. Collectively, these data suggest that sustained reproductive and metabolic alterations may result in female mice from a transient exposure to T during a narrow postnatal developmental window.