Maternal obesity aggravates the abnormality of porcine placenta by increasing N6-methyladenosine

Background The growing prevalence of overweight or obese pregnancies shows an increasing risk for aberrant fetal growth and postnatal complications. Maternal obesity is associated with low birth weight (LBW) of piglets. However, the development of LBW from maternal obesity is not well understood. Objective This study attempts to investigate the novel RNA modification N-6-methyladenosine (m(6)A) in the placenta tissues by using sows with high backfat thickness as a model for obese pregnancy. Subjects/methods Forty four placentas from eight sows (backfat thickness z21 mm) were divided into four groups by piglet weight, with group 1 being LBW group (<1.0 kg), group2 (1.0-1.4 kg), group3 (1.4-1.6 kg), and group4 (>1.6 kg) as the comparative groups of normal birth weight. QPCR was used to measure the mRNA levels of the genes and western blot was used to test the content of proteins. At the same time, LC-MS/MS method was built to test the content of m(6)A modification in the placental RNA, and finally MeRIP-QPCR technology was employed to check the specific m(6)A modification in the key genes. Results Compared with the comparative groups, the expression levels of PPAR gamma, VEGFA, ABHD5, and GPR120 in both mRNA and protein decreased noticeably in the LBW group. It was also observed that the density of the H&E stained vessels became attenuated in LBW group. Importantly, for the first time, the increased m(6)A levels were found in LBW placentas. Lower protein level of FTO (the key demethylase of m(6)A) was observed in LBW placentas, whereas no difference was found among the four groups in the expression levels of METTL3, the main methyltransferase of m(6)A. By using MeRIP-QPCR technology, the m(6)A modification in PPAR gamma, VEGFA, ABHD5, and GPR120, as well as FTO, was considerably enhanced in the placentas from LBW group. Conclusion We infer that in maternity obesity, the higher m(6)A modification displayed in the genes related to placental development, lipid metabolism and angiogenesis may result in the down regulation of these genes, which could be associated with m(6)A demethylase FTO.