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围受孕时期及辅助生殖过程中的表观遗传影响

Epigenetic Influences During the Periconception Period and Assisted Reproduction.

作者信息

Amoako Akwasi A, Nafee Tamer M, Ola Bolarinde

机构信息

Department of Reproductive Medicine, Central Manchester, University Hospitals NHS Foundation Trust, St Mary's Hospital, Oxford Road, Manchester, UK.

Sheffield Teaching Hospitals NHS Foundation Trust, University of Sheffield, Sheffield, UK.

出版信息

Adv Exp Med Biol. 2017;1014:15-39. doi: 10.1007/978-3-319-62414-3_2.

Abstract

The periconception period starts 6 months before conception and lasts until the tenth week of gestation. In this chapter, we will focus on epigenetic modifications to DNA and gene expression within this period and during assisted reproduction. There are two critical times during the periconception window when significant epigenetic 'reprogramming' occur: one during gametogenesis and another during the pre-implantation embryonic stage. Furthermore, assisted conception treatments, laboratory protocols and culture media can affect the embryo development and birth weights in laboratory animals. There is, however, an ongoing debate as to whether epigenetic changes in humans, causing embryo mal-development, placenta dysfunction and birth defects, result from assisted reproductive technologies or are consequences of pre-existing medical and/or genetic conditions in the parents. The periconception period starts from ovarian folliculogenesis, through resumption of oogenesis, fertilisation, peri-implantation embryo development, embryogenesis until the end of organogenesis. In men, it is the period from spermatogenesis to epididymal sperm storage and fertilisation. Gametes and developing embryos are sensitive to environmental factors during this period, and epigenetic modifications can occur in response to adverse lifestyles and environmental factors. We now know that lifestyle factors such as advanced parentage age, obesity or undernutrition, smoking, excessive alcohol and caffeine intake and recreational drugs used during gamete production and embryogenesis could induce epigenetic alterations, which could impact adversely on pregnancy outcomes and health of the offspring. Furthermore, these can also result in a permanent and irreversible effect in a dose-dependent manner, which can be passed on to the future generations.

摘要

围孕期始于受孕前6个月,持续至妊娠第10周。在本章中,我们将重点关注此期间以及辅助生殖过程中DNA的表观遗传修饰和基因表达。在围孕期窗口期间有两个关键时期会发生显著的表观遗传“重编程”:一个是在配子发生过程中,另一个是在植入前胚胎阶段。此外,辅助受孕治疗、实验室方案和培养基会影响实验动物的胚胎发育和出生体重。然而,关于人类的表观遗传变化导致胚胎发育不良、胎盘功能障碍和出生缺陷,是辅助生殖技术的结果还是父母先前存在的医学和/或遗传状况的后果,目前仍在争论中。围孕期从卵巢卵泡发生开始,经过卵子发生的恢复、受精、植入前胚胎发育、胚胎发生直至器官发生结束。对男性而言,是从精子发生到附睾精子储存和受精的时期。在此期间,配子和发育中的胚胎对环境因素敏感,表观遗传修饰可能会因不良生活方式和环境因素而发生。我们现在知道,诸如父母年龄偏大、肥胖或营养不良、吸烟、过量饮酒和咖啡因摄入以及在配子产生和胚胎发生期间使用消遣性药物等生活方式因素,可能会诱导表观遗传改变,这可能会对妊娠结局和后代健康产生不利影响。此外,这些影响还可能以剂量依赖的方式导致永久性和不可逆的效应,并可遗传给后代。

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