Jie Dong1, Liang Wen1, Xiangyu Guo1, Xifeng Xiao1, Feng Jiang1, Bo Li1, Ni Jin1, Jingjing Wang1, Xin Wang1, Shuqiang Chen2, Xiaohong Wang3. 1. Department of Obstetrics and Gynaecology, Tangdu Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China. 2. Department of Obstetrics and Gynaecology, Tangdu Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China. Electronic address: chenshuqiang2012@163.com. 3. Department of Obstetrics and Gynaecology, Tangdu Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, China. Electronic address: wangxh-99919@163.com.
Abstract
OBJECTIVE: In the mouse model, manipulations of assisted reproductive technology (ART) can lead to enlarged placentas and influence the expression of glucose transporters (GLUTs) in placentas during mid-to late-gestation. Expression of imprinted genes which plays a vital role in placental growth and function, is also vulnerable to be affected by ART. However, it is uncertain whether those abnormal changes presented in ART mouse placentas also occur in human ART placentas. METHODS: We compared the expression of GLUT family genes (SLC2A1- SLC2A13), mTOR activity, the expression of four imprinted genes (H19, IGF2, CDKN1C and PHLDA2), and KCNQ1OT1 methylation in human placentas conceived naturally or by ART. RESULTS: Our data showed that the placental weight and birthweight were similar between NC (n = 20) and ART group (n = 20). We found that up-regulated mRNA expression of GLUTs and elevated GLUT1 protein level occurred in human ART placentas with unchanged mTOR activity. And we found that mRNA and protein expression of PHLDA2 were significantly increased in ART placentas compared with placentas from natural pregnancies. Additionally, we revealed that ART placentas had increased expression of KCNQ1OT1 which negatively controls PHLDA2 expression. CONCLUSION: This study reveals that the increased expression of GLUTs occurs in human ART placentas with normal mTOR activity. The down-regulated expression of imprinted gene PHLDA2 may account for the up-regulation of GLUTs. Those adaptive changes in ART placentas may explain why most of ART offspring have normal birth weight at born.
OBJECTIVE: In the mouse model, manipulations of assisted reproductive technology (ART) can lead to enlarged placentas and influence the expression of glucose transporters (GLUTs) in placentas during mid-to late-gestation. Expression of imprinted genes which plays a vital role in placental growth and function, is also vulnerable to be affected by ART. However, it is uncertain whether those abnormal changes presented in ART mouse placentas also occur in human ART placentas. METHODS: We compared the expression of GLUT family genes (SLC2A1- SLC2A13), mTOR activity, the expression of four imprinted genes (H19, IGF2, CDKN1C and PHLDA2), and KCNQ1OT1 methylation in human placentas conceived naturally or by ART. RESULTS: Our data showed that the placental weight and birthweight were similar between NC (n = 20) and ART group (n = 20). We found that up-regulated mRNA expression of GLUTs and elevated GLUT1 protein level occurred in human ART placentas with unchanged mTOR activity. And we found that mRNA and protein expression of PHLDA2 were significantly increased in ART placentas compared with placentas from natural pregnancies. Additionally, we revealed that ART placentas had increased expression of KCNQ1OT1 which negatively controls PHLDA2 expression. CONCLUSION: This study reveals that the increased expression of GLUTs occurs in human ART placentas with normal mTOR activity. The down-regulated expression of imprinted gene PHLDA2 may account for the up-regulation of GLUTs. Those adaptive changes in ART placentas may explain why most of ART offspring have normal birth weight at born.
Authors: Lilian M Martinelli; Antonio Carucci; Victor J H Payano; Kristin L Connor; Enrrico Bloise Journal: Reprod Sci Date: 2022-02-08 Impact factor: 3.060