体外培养增加了通过辅助生殖技术产生的小鼠胚胎胎盘组织中印迹基因随机表观遗传错误的频率。

In vitro culture increases the frequency of stochastic epigenetic errors at imprinted genes in placental tissues from mouse concepti produced through assisted reproductive technologies.

作者信息

de Waal Eric, Mak Winifred, Calhoun Sondra, Stein Paula, Ord Teri, Krapp Christopher, Coutifaris Christos, Schultz Richard M, Bartolomei Marisa S

机构信息

Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

出版信息

Biol Reprod. 2014 Feb 6;90(2):22. doi: 10.1095/biolreprod.113.114785. Print 2014 Feb.

Abstract

Assisted reproductive technologies (ART) have enabled millions of couples with compromised fertility to conceive children. Nevertheless, there is a growing concern regarding the safety of these procedures due to an increased incidence of imprinting disorders, premature birth, and low birth weight in ART-conceived offspring. An integral aspect of ART is the oxygen concentration used during in vitro development of mammalian embryos, which is typically either atmospheric (~20%) or reduced (5%). Both oxygen tension levels have been widely used, but 5% oxygen improves preimplantation development in several mammalian species, including that of humans. To determine whether a high oxygen tension increases the frequency of epigenetic abnormalities in mouse embryos subjected to ART, we measured DNA methylation and expression of several imprinted genes in both embryonic and placental tissues from concepti generated by in vitro fertilization (IVF) and exposed to 5% or 20% oxygen during culture. We found that placentae from IVF embryos exhibit an increased frequency of abnormal methylation and expression profiles of several imprinted genes, compared to embryonic tissues. Moreover, IVF-derived placentae exhibit a variety of epigenetic profiles at the assayed imprinted genes, suggesting that these epigenetic defects arise by a stochastic process. Although culturing embryos in both of the oxygen concentrations resulted in a significant increase of epigenetic defects in placental tissues compared to naturally conceived controls, we did not detect significant differences between embryos cultured in 5% and those cultured in 20% oxygen. Thus, further optimization of ART should be considered to minimize the occurrence of epigenetic errors in the placenta.

摘要

辅助生殖技术(ART)已使数百万生育能力受损的夫妇能够生育子女。然而,由于ART受孕后代中印记障碍、早产和低出生体重的发生率增加,人们对这些程序的安全性日益担忧。ART的一个重要方面是哺乳动物胚胎体外发育过程中使用的氧气浓度,通常为大气氧浓度(约20%)或低氧浓度(5%)。两种氧张力水平都已被广泛使用,但5%的氧气可改善包括人类在内的几种哺乳动物的植入前发育。为了确定高氧张力是否会增加接受ART的小鼠胚胎中表观遗传异常的频率,我们测量了体外受精(IVF)产生的胚胎在培养过程中暴露于5%或20%氧气的胚胎和胎盘组织中几个印记基因的DNA甲基化和表达情况。我们发现,与胚胎组织相比,IVF胚胎的胎盘表现出几种印记基因异常甲基化和表达谱的频率增加。此外,IVF来源的胎盘在检测的印记基因上表现出多种表观遗传谱,这表明这些表观遗传缺陷是由随机过程产生的。尽管与自然受孕的对照组相比,在两种氧浓度下培养胚胎都会导致胎盘组织中表观遗传缺陷显著增加,但我们未检测到在5%氧气中培养的胚胎与在20%氧气中培养的胚胎之间存在显著差异。因此,应考虑进一步优化ART,以尽量减少胎盘中表观遗传错误的发生。

相似文献

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索