In support of the placental programming hypothesis: Placental endocrine insufficiency programs atypical behaviour in mothers and their offspring

Abstract

Prenatal adversity, which is estimated to impact more than half of all pregnancies in the UK, compromises fetal growth increasing the chances of stillbirth, prematurity and infant mortality. Beyond these immediate and highly visible problems, infants that survive carry the invisible burden of increased risk of some of the most common and pervasive diseases that impact human populations. In utero exposure to depression and anxiety is one adversity that has been linked to these poorer outcomes suggesting that maternal mood disorders drive the outcomes. However, recent studies in animal models suggest that both the maternal mood disorders and detrimental outcomes for children could be the result of the same underlying placental pathology. In these studies, genetically wild-type rodent mothers exposed to placental endocrine insufficiency engaged in less pup-focused behaviours and less self-care. Genetically wild-type rodent offspring raised in this abnormal environment exhibited increased anxiety-like behaviours with male offspring additionally exhibiting deficits in cognition, atypical social behaviour with some evidence of depressive-like symptoms. This work establishes the experimental paradigm that placental endocrine insufficiency alone is sufficient to drive atypical behaviour in both mothers and their offspring. While there is some data to suggest this phenomenon is relevant to human pregnancy, considerably more work is required.

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