The Effects of a Hyperandrogenic Prenatal Environment on Early and Later Life Social and Non-Social Behaviour
Gonadal sex hormones, such as testosterone (T) and estradiol (E2), are instrumental for sexual differentiation. During development, these hormones give rise to sexually dimorphic features and behaviour. Subsequently, hormones have activational effects on sexually dimorphic behaviors throughout adulthood. Most behavioral research has focused on activational effects, leaving the developmental effects less understood. In particular, the developmental effects of T on social behaviors, such as social approach and social recognition (SR), as well as non-SR memory (object recognition (OR), are little understood. In this study, we sought to elucidate how exposure to heightened levels of prenatal T interacts with later-life activational effects to enhance or impair social and non-social cognition. We treated pregnant CD1 mice with 10µg of testosterone propionate (TP) or the oil injection vehicle, on embryonic days 12, 14 and 16. Prior to puberty (PD 34-42), mice were tested in (A) SA: measuring innate preference for sociability; (B) SR: measuring the ability for an individual to discern a novel conspecific from previously encountered mouse; and (C) OR: measuring item declarative/recognition memory. Mice were then gonadectomised (GDX) or sham operated and given hormone replacement (12.5µg E for females or T for males). Mice were re-tested in SA, SR, and OR as adults. Overall, all mice showed an innate preference for the social stimulus (measured by SA). Pre-puberty we found that increased T exposure in-utero had an enhancing effect on males in OR and in both males and females in SR. In adulthood, we found that males, but not females, who received T replacement during adulthood and were exposed to heightened levels of prenatal TP performed worse in the OR test than T-replaced males who were not prenatally TP exposed. Prenatal control T replacement males outperformed prenatal control female E replacement in OR. SR, by contrast, was impaired in males. In GDX males that did not receive T replacement, prenatal TP exposure worsened performance compared to males that did not receive prenatal T. Overall, we found that exposure to a heightened levels of TP in-utero interacts with sex hormone manipulations in adulthood to produce sexually differentiated effects on OR and SR.