Introduction: Maternal distress, including poorer life satisfaction, increased anxiety and depression (A&D) symptoms, are worse in Severely Obese (SO) than lean pregnancy and may alter placental genes regulating foetal glucocorticoid exposure and placental growth. We hypothesised that the associations between increased maternal distress with changes in placental mRNA levels leading to a reduced placental barrier to maternal glucocorticoids, and altered placental IGF2, are more pronounced in SO pregnancy. We also considered any sex-specific effects.
Methods: Placental mRNA levels of genes regulating glucocorticoids including 11β-HSDs, NR3C1, NR3C2, ABC transporters, mTOR and IGF2 family were measured in term placental samples from 43 lean (BMI ≤25 kg/m2) and 50 SO (BMI ≧40 kg/m2) women, in whom A&D symptoms were prospectively evaluated during pregnancy.
Results: The mRNA levels of genes with a similar role in regulating foetal glucocorticoid exposure were strongly inter-correlated (all 0.2≤ ≤0.7, P≤0.05). Increased A&D symptoms associated with increased NR3C2 and IGF2 in both lean and SO group (all ≤0.3, P≤0.05). Increased maternal distress was associated with higher ABCB1 and ABCG2 mRNA levels in SO but lower ABCB1 and higher 11β-HSD1 mRNA levels in lean (all P≤0.05) suggesting a protective adaptive response in SO placentas. Increased maternal distress associated with reduced mRNA levels of ABCB1, ABCG2, 11β-HSD2, NR3C1and IGF2 in female placentas (all ≤0.29, P≤0.05), but not in males.
Conclusion: The observed sex differences in placental responses suggest greater vulnerability of female foetuses to maternal mood with potentially greater fetal glucocorticoid exposure and excess IGF2. Further studies are needed to test whether this translates to potentially greater negative outcomes of maternal distress in females in early childhood.
Disclosure: We are grateful to the generous funding from Tommys the Baby Charity and Principal Development Scholarship, Charles Darwin Scholarship and Global Research Scholarship, University of Edinburgh, Scotland.