Endocrine Abstracts

Obesity in pregnancy is associated with an increased risk of complications for mother and child. Epigenetic modifications have been proposed as an important underlying mechanism. As the placenta plays a key role in fetal nutrition and metabolism we hypothesized there would be placental DNA methylation differences between lean and obese placenta. DNA methylation array (Human Methylation 450K) was performed on placentas from n=31 obese (BMI>40 kg/m²) and n=29 lean (BMI<25 kg/m²) women. MiR-411 and FABP1, with false discovery rate (FDR) adjusted P<0.05, were selected for validation of DNA methylation differences by Pyrosequencing and measurement of mRNA levels by RT-qPCR. The mean (SD) percentage DNA methylation at miR-411 and FABP1 was significantly higher in obese placenta vs lean (68.9 (13.4)% vs 58.9 (15.8)%, P=0.01 and 89.7(2.76)% vs 85.8(7.16)%, P=0.01, respectively). MiR-411 DNA methylation was significantly higher in placenta from non-smoking obese vs non-smoking lean (70.42(9.6)% vs 58.63(17.4)%, P=0.02) women. MiR-411 DNA methylation percentage was highest in placentas from male babies born to obese mothers. There were no correlations between methylation levels and mRNA levels of miR-411 in either obese or lean placentas (miR-411 obese r=0.21, P=0.32; lean r=−0.32, P=0.14). MiR-411 mRNA levels were significantly higher in current smokers vs non-smokers and ex-smokers (3.61(3.2) vs 1.3(1.2) vs 1.13(0.7), P≤0.05). Infant BMI was positively correlated with mRNA levels of miR-411 in the lean but not obese group (lean r=0.636, P=0.003; obese r=0.021, P=0.931). In conclusion, DNA methylation and gene expression differ between lean and obese placenta, but are also influenced by maternal environment, fetal sex and infant BMI. The explanation for the lack of association of DNA methylation changes and gene expression changes is not known but may be due to the small magnitude of the DNA methylation changes. Further studies are needed to understand the functional outcomes of these DNA methylation changes.