Placental FKBP51 mediates a link between second trimester maternal anxiety and birthweight in female infants

Katie L Togher,Gerard Clarke,Ali S Khashan,Gerard W O’Keeffe,Louise C Kenny

doi:10.1038/s41598-018-33357-3

Abstract

Prenatal distress is associated with adverse outcomes in affected offspring. Alterations in placental glucocorticoid signalling and subsequent foetal overexposure to glucocorticoids have been implicated as an underlying mechanism. Infant sex is emerging as an important factor in disease susceptibility. This study aimed to examine the effects of maternal distress across pregnancy on birth outcomes and placental glucocorticoid genes in a sex-dependent manner. Participants completed psychological distress questionnaires throughout pregnancy. Placental HSD11B2, NR3C1 and FKBP51 were analysed by real time PCR and cortisol was measured in new-born hair. Second trimester stress was negatively correlated with birthweight in males and positively correlated with placental NR3C1 mRNA in females. Second trimester anxiety was negatively correlated with birthweight and placental FKBP51 mRNA in females. In mediation analysis, placental FKBP51 mRNA expression was found to mediate the link between prenatal anxiety and birthweight. New-born cortisol was negatively correlated with second trimester anxiety and positively correlated with female placental FKBP51 mRNA levels. Again, FKBP51 mRNA was found to mediate the link between anxiety and new-born cortisol. These results highlight a role for FKBP51 in the placental response to prenatal distress in females. The precise role that placental FKBP51 has in foetal and infant development has not been extensively studied and warrants further investigations.

Highlights

There is a large body of evidence showing that the in utero experience is a critical determinant of future health[1,2,3]
These include an increased risk of adverse obstetric outcomes including caesarean delivery, preterm birth (PTB), low birth weight (LBW) and babies who are small for gestational age (SGA)[4,5,11,12,13,14]
We found that the glucocorticoid receptor NR3C1 is upregulated by third trimester distress[4]

Summary

Introduction

There is a large body of evidence showing that the in utero experience is a critical determinant of future health[1,2,3]. These data have shown that approximately one in seven women experience clinically significant levels of prenatal maternal psychological distress during pregnancy This is important as numerous epidemiological studies have reported that exposure to prenatal maternal psychological distress is a risk factor for a range of adverse short and long-term outcomes in affected offspring. Increased methylation of placental FKBP51 has been reported following early third trimester stress[33], we previously observed no change in FKBP51 expression following distress in the third trimester[4], indicating the need to examine other trimesters These data suggest that prenatal maternal psychological distress may alter molecular mechanisms that regulate foetal exposure to maternal cortisol. We undertook causal mediation analysis to determine whether any changes in the placental expression of these genes were associated with birth outcomes using gender-sensitive methodology

Objectives

Methods

Results

Conclusion