During the prenatal period maternal stress exposure can have detrimental ‘programming’ effects on the brain and behaviour of the offspring. We have used a social stress model (repeated exposure to an unfamiliar lactating rat during the last week of pregnancy) to investigate the adverse consequences of stress exposure during pregnancy on the offspring’s brain and behaviour and the possible underlying mechanisms. We have found prenatally stressed (PNS) offspring generally display increased neuroendocrine responses to stress (both physical and psychological), increased anxiety-related behaviour , disrupted glucose-insulin and lipid homoeostasis  and cognitive deficits. Critically, many of these adverse consequences of prenatal stress exposure are sex-specific. For example, PNS males, but not females exhibit increased anxiety-like behaviour; whereas both males and females display enhanced hypothalamo-pituitary-adrenal (HPA) axis responses to stress . Given neurosteroids are anxiolytic and suppress stress responses, we investigated whether deficits in neurosteroid production may explain some of the adverse phenotypes in PNS rats. 5α-reductase (a key enzyme in neurosteroid generation) mRNA levels were significantly lower in the brainstem of both male and female PNS rats compared with controls. Moreover, peripheral administration of the 5α-reduced metabolites of testosterone (androstandiol) or progesterone (allopregnanolone) normalised stress responses in male and female PNS offspring, respectively, and androstandiol reduced anxiety-like behaviour PNS males. Targeted up-regulation of 5α-reductase (and 3α-hydroxysteroid dehydrogenase) mRNA expression in the brainstem also normalised stress-induced HPA responses in PNS rats. Hence, down-regulation of neurosteroid production in the brain may explain enhanced stress responses and anxious behaviour in PNS offspring.
These programming effects may be considered adaptive, enabling the offspring to better cope with unfavourable conditions e.g. enhanced behavioural and neuroendocrine responses to stress may reflect greater vigilance to environmental threats. However, this programming comes at a cost, particularly when there is a mismatch between the predicted and the actual postnatal environment.