Excess neonatal testosterone causes male-specific social and fear memory deficits in wild-type mice

Abstract

AbstractNeurodevelopmental disorders (ND) disproportionately affect males compared to females, and Autism Spectrum Disorder (ASD) in particular exhibits a 4:1 male bias. The biological mechanisms of this female protection or male susceptibility have not been identified. There is some evidence to suggest that fetal/neonatal gonadal hormones, which play pivotal roles in many aspects of development, may contribute. Here, we investigate the role of testosterone administration during a critical period of development, and its effects on social approach and fear learning in C57BL/6J wildtype mice. Male, but not female mice treated with testosterone on the day of birth (PN0) exhibited deficits in both social behavior and contextual fear conditioning, whereas mice treated with the same dose of testosterone on postnatal day 18 (PN18) did not display such impairments. Testosterone administration did not induce anxiogenic effects or lead to changes in weight compared to the testosterone-treated group. These impairments are relevant to ND and may help identify novel treatment targets.HighlightsMale mice treated with testosterone at birth displayed reduced social approach behavior as juveniles and demonstrated impairments in contextual fear conditioning as adults, compared to mice treated with vehicle oil.Testosterone treatment on postnatal day 18 did not affect social approach or fear memory.This single dose of testosterone on PN0 did not induce anxiety-like behavior in testosterone-treated mice compared to vehicle-treated control mice.Neonatal testosterone administration did not result in a weight change compared to veh-treated mice.