Background: Maternal obesity during pregnancy is associated with adverse effects on fetal growth and development. As the placenta is a key organ regulating fetal growth, we hypothesized that maternal obesity is associated with altered placental expression and DNA methylation of genes regulating fetal growth and glucocorticoid metabolism and aimed to investigate this in first trimester (F; <12 weeks gestation) and term (T;>37 weeks gestation) placental tissues.
Methods: Thirty-six F samples were obtained from women (body mass index (BMI) 18.745.0 kg/m2) undergoing termination of pregnancy at a mean of 9 weeks gestation (± 3.5 days; viable intrauterine pregnancy confirmed by ultrasound). Forty T samples matched for age, gestation, gender and birthweight were collected from lean (BMI<25 kg/m2) and obese (BMI>30 kg/m2) women undergoing elective caesarean section. Ethical approval and written informed consent were obtained. mRNA levels of six candidate control genes, insulin-like growth factor 2 (IGF2), glucocorticoid receptor (GR) and 11 beta-hydroxysteroid dehydrogenase type 2 (11BHSD2) were measured by real time PCR. DNA methylation of these genes was measured by pyrosequencing.
Results: TATA Box Binding Protein (TBP) was identified as a suitable control gene as expression was not related to maternal BMI (r2=0.004, P=0.92) or offspring gender (r2=0.04, P=0.23). In F, maternal BMI was positively correlated with expression of 11BHSD2 (r2=0.21, P<0.01), GR (r2=0.21, P<0.05) and IGF2 (r2=0.12, P<0.05), but no significant correlation was found between BMI and DNA methylation for any of the genes studied. No significant differences in gene expression or methylation were observed between lean and obese in T placenta. Conclusions Maternal obesity is associated with changes in expression, but not methylation, of key genes in fetal growth and glucocorticoid pathways in first trimester but not term placental tissue. These studies indicate there may be a window in placental development during the first trimester that is sensitive to maternal obesity status.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.