Maternal BMI Modulates Placental Expression of Lipid Transport, Metabolism and Innate Immune Response Genes at Term (OR35-01-19)

Abstract

ObjectivesMaternal body composition during pregnancy is an important determinant of offspring obesity risk. One hypothesized mechanism linking maternal and offspring obesity is via alterations in placental gene expression and function. Here we examined the influence of early pregnancy maternal obesity on placental gene expression at term using transcriptomic approaches. MethodsWe examined placenta collected from a longitudinal observational study of mothers and infants where maternal anthropometrics, body composition, dietary intake (3 d food records) and other variables were collected every trimester in the mothers. Placentas were collected within 30 min of delivery and archived for molecular and histologic analysis. For the current analyses, transcriptomic analysis of villous placental tissues from normal weight (NW, N = 71), and overweight/obese women (OW, N = 70, based on BMI < 10 wk of pregnancy) were performed using strand-specific mRNA-seq. Data analyses were carried out using the STAR-Seqmonk-Limma pipeline. ResultsRNA-seq analysis provided quantitative information on expression of 13,831 transcripts (> 2 counts/million in 50% of samples). Assessment via principal component analysis identified significant effects of maternal BMI (in male infants), infant sex and mode of delivery on placental gene expression. Linear regression of mRNA expression with early pregnancy maternal BMI (adjusting for mode of delivery and sex) identified significant association with 230 transcripts (P < 0.05). Likewise, regression analysis of maternal body fat identified significant associations with 271 genes, with 99 genes shared in common between BMI and body fat. These transcripts were enriched for cell morphogenesis, fatty acid biosynthetic and lipid transport related pathways. Of note, expression of ABCG1 (cholesterol transporter), MMP1, CEBPα and PRKAG2 (AMPKγ2) were negatively associated with maternal BMI (P < 0.05). mRNA expression of MHC Class II antigens DRB1 and DRB5, critical in antigen presentation and immune response was increased (> 1.8-fold) in male placenta of OW women. ConclusionsIn a large cohort of well-characterized pregnant women maternal adiposity status in early pregnancy influences term placental expression of genes involved in lipid transport, metabolism and innate immune response in a sexually dimorphic manner. Funding SourcesSupported by USDA-ARS Project 6026-51000-010-05S.