Assisted reproduction causes placental maldevelopment and dysfunction linked to reduced fetal weight in mice.

Shuqiang Chen,Fang-Zhen Sun,Xiuying Huang,Na Tang,Baoyi Zhu,Bo Li,Xiaohong Wang

doi:10.1038/srep10596

Abstract

Compelling evidence indicates that stress in utero, as manifested by low birth weight (LBW), increases the risk of metabolic syndrome in adulthood. Singletons conceived by assisted reproductive technology (ART) display a significant increase in LBW risk and ART offspring have a different metabolic profile starting at birth. Here, used mouse as a model, we found that ART resulted in reduced fetal weight and placental overgrowth at embryonic day 18.5 (E18.5). The ART placentae exhibited histomorphological alterations with defects in placental layer segregation and glycogen cells migration at E18.5. Further, ART treatments resulted in downregulation of a majority of placental nutrient transporters and reduction in placental efficiency. Moreover, the ART placentae were associated with increased methylation levels at imprinting control regions of H19, KvDMR1 and disrupted expression of a majority of imprinted genes important for placental development and function at E18.5. Our results from the mouse model show the first piece of evidence that ART treatment could affect fetal growth by disrupting placental development and function, suggests that perturbation of genomic imprinting resulted from embryo manipulation may contribute to these problems.

Highlights

Larger placentae and higher placental weight/birth weight ratios were found in assisted reproductive technology (ART) pregnancies[15]
To determine the impact of ART procedures on fetal and placental development, mouse blastocyts were generated under three different experimental conditions: 1) In the IVC group, eggs were fertilized in vivo, collected at the one-cell stage and cultured in vitro in KSOM+ AA to the blastocyst stage
We show that ART is a significant factor responsible for abnormal placentation and function accompanied by genomic imprinting perturbation in the placenta at mid-to-late gestation in the mouse

Summary

Introduction

Larger placentae and higher placental weight/birth weight ratios were found in ART pregnancies[15] These placental abnormalities may contribute to abnormal fetal growth and are an important cause of LBW. With respect to loss-of-imprinting, both maternally and paternally expressed imprinted genes in placentae derived from in vitro manipulated mouse embryos were modified at embryonic day 10.5 (E10.5)[22]. It is still not known whether perturbation in genomic imprinting induced by ART affects placentation and placental function during mid-to-late-gestation. We provide evidence that suboptimal ART conditions can disrupt mammalian epigenetic reprogramming and result in perturbation of placental development and function, which may in turn contribute to reduced fetal weight in mice

Methods

Results

Conclusion