Low dose prenatal testosterone exposure decreases the corticosterone response to stress in adult male, but not female, mice

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Gonadal steroid hormones affect the organization of the brain during sensitive periods of development, resulting in sex differences in the neuroendocrine function and behaviour of the offspring. Although alterations in developmental testosterone exposure have been hypothesized to play a role in male-biased neurodevelopmental disorders, the underlying mechanisms remain unknown. The present study investigated the hypothesis that early prenatal exposure to low concentrations of testosterone might affect the control of stress responses in later life. Pregnant CD1 mice were treated with 10 μg of testosterone propionate or sesame oil control on embryonic days 12, 14, and 16. Effects on development were assessed by measuring litter size, composition and weight, first appearance of hair, eye and ear opening, and adult body weight. Reproductive development was assessed by measuring testosterone levels in neonatal and adult males, gonad weights in both sexes and reproductive cyclicity in females. The function of the hypothalamic-pituitary-adrenal axis was determined by measuring corticosterone in hair samples from juvenile animals, as well as in plasma following restraint stress in adulthood. Prenatal testosterone treatment had no significant effects on any of the overall developmental or reproductive endpoints assessed. However, in adulthood, corticosterone responses to restraint stress were reduced in the male but not the female offspring, with no significant effect on basal corticosterone levels in either sex. Thus, a small prenatal increase in maternal testosterone may be sufficient to produce a lasting sex-specific alteration in the sensitivity of the male HPA axis to stress.