Maternal obesity aggravates the abnormality of porcine placenta by increasing N-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 N6-methyladenosine (mA) 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 ≥21 mm) were divided into four groups by piglet weight, with group1 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 mA modification in the placental RNA, and finally MeRIP-QPCR technology was employed to check the specific mA modification in the key genes.

RESULTS

Compared with the comparative groups, the expression levels of PPARγ, 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 mA levels were found in LBW placentas. Lower protein level of FTO (the key demethylase of mA) was observed in LBW placentas, whereas no difference was found among the four groups in the expression levels of METTL3, the main methyltransferase of mA. By using MeRIP-QPCR technology, the mA modification in PPARγ, 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 mA 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 mA demethylase FTO.