Effects of assisted reproductive technology on the level of DNA methylation in human placenta

Abstract

Objective To explore whether assisted reproductive technology (ART) affects the infant body weight, the placental weight, ratio of infant/placental weight, the mean DNA methylation level and the expression level of DNA methyltransferase (DNMT) family and ten-eleven translocation (TET) family. Methods The infant weight, placental weight, ratio of infant/placental weight were compared between 35 singleton full-term neonates derived from ART-born (ART group) and 36 singleton full-term neonates derived from naturally-born (negative control group, NC group). To avoid the effects of age factors, 20 placentas were selected from each group to detect the mean DNA methylation level by ELISA and the expressions of DNMT family (DNMT1, DNMT3A, DNMT3B) and TET family (TET1, TET2, TET3) by RT-qPCR. Results The infant weight [(3 650.50±393.84) g] and placental weight [(633.05±98.58) g] were significantly increased in ART group compared with NC group [(3 339.50±377.01) g, (563.00±85.60) g]. The mean DNA methylation level of placenta in ART group (1.22%±0.45%) was significantly lower than that in NC group (2.08%±0.98%). The mRNA expression levels of DNMT3B, TET1, TET2, TET3 were up-regulated in ART group (4.61±1.06, 4.66±1.06, 4.99±1.09, 4.92±1.13) compared with control group (1.23±0.55, 1.27±0.56, 1.47±0.50, 1.41±0.61) (P<0.05), though there were no significant differences in the mRNA expression lever of DNMT1 and DNMT3A. Conclusion ART can lead to the overgrowth of placenta in the late stage of human pregnancy and a low level of DNA methylation in the placenta, which may due to the up-regulated expression level of DNMT3B, TET1, TET2, TET3. Key words: Assisted reproductive technology (ART); Placenta; Methylation; DNA methyltransferase (DNMT); Ten-eleven translocation (TET)