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

Abstract

New findings: What is the topic of this review? More than half of all pregnancies in the UK are exposed to adversity linked to increased problems in pregnancy for mothers and adverse outcomes for their children, but we do not know the mechanism(s) underpinning these relationships. What advances does it highlight? Studies in mice prove that placental endocrine insufficiency driven by genetic manipulation of imprinted genes in the offspring can concurrently drive fetal growth restriction, alterations in maternal caregiving and aberrant behaviour in wild-type offspring exposed to an adverse environment. This suggests that placental endocrine insufficiency might contribute to the co-morbidity of low birth weight, maternal depression and neurodevelopmental disorders observed in human populations.

Abstract: Prenatal adversity, which is estimated to impact more than half of all pregnancies in the UK, compromises fetal growth and increases 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 the 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 and atypical social behaviour, with some evidence of depressive-like symptoms. This work establishes experimentally that placental endocrine insufficiency alone is sufficient to drive atypical behaviour in both mothers and their offspring. Although there are some data to suggest that this phenomenon is relevant to human pregnancy, considerably more work is required.

Keywords: fetal growth restriction; maternal depression; neurodevelopment; placental endocrine insufficiency.