Dynamic integrated analysis of DNA methylation and gene expression profiles in in vivo and in vitro fertilized mouse post-implantation extraembryonic and placental tissues
Dynamic integrated analysis of DNA methylation and gene expression profiles in in vivo and in vitro fertilized mouse post-implantation extraembryonic and placental tissues
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体内和体外受精小鼠植入后胚胎外和胎盘组织 DNA 甲基化和基因表达谱的动态集成分析
DOI：
10.1093/molehr/gaw028
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发表时间：
2016
影响因子：
4
通讯作者：
An Lei
中科院分区：
文献类型：
--
作者：
Tan Kun;Zhang Zhenni;Miao Kai;Yu Yong;Sui Linlin;Tian Jianhui;An Lei
体外受精（IVF）是最有效和最成功的辅助生殖技术之一。它被广泛用于治疗人类不育症，也用于动物繁殖和繁殖。虽然IVF通常被认为是一种安全和成功的技术，但存在若干IVF相关的安全性问题，例如妊娠丢失、早产、出生体重较低和出生缺陷，以及年龄相关疾病（例如心脏病、糖尿病或高血压）的风险较高（Bergh et al. 1999; Racowsky，2002; Schieve等人，2002; Klemetti等人，2006; Ceelen等人，2008; Reefhuis等人，2009年; Wen等人，2012;汉森等人，二〇一三年;许多胎儿研究表明，IVF过程可能会破坏一系列生物学过程，包括遗传信息处理（Giritharan et al.，2007; Fernando-Gonzalez等人，2009; Driver等人，2012）、表观遗传修饰（Deshmukh等人，2011;奥利弗等人，2012）、氨基酸和能量代谢（Nie等人，2013年; Ren等人，2015）和细胞骨架组织（Tan等人，2015年）。此外，胎盘研究可能有助于更全面地了解IVF诱导的胚胎或后代并发症的潜在机制，因为已知胎盘在胎儿发育中起重要作用。胎盘提供母胎界面，并且对于气体、营养物和废物的交换至关重要，以支持发育中的胎儿。它也是妊娠相关激素和生长因子的重要来源，并参与胎儿免疫耐受（Rossant和Cross，2001）。胎盘形成缺陷和随后的胎盘功能不全可导致母体和胎儿不良妊娠结果，并且还可与产后疾病风险相关（Barker et al.，1990年; Seckl和Holmes，2007年）。最近的研究表明，IVF可以改变胎盘发育，影响结构、大小和经胎盘营养转运能力（Delle Piane et al.，2010; Bloise等人，2012; Haavaldsen等人，2012年; Tan等人，2016年）。此外，高通量基因表达和蛋白质组学分析研究可用于理解IVF相关并发症中涉及的胎盘机制（Fauque等人，2010 a; Sui等人，2014年）。在人类和小鼠中，在植入后胚胎发育期间，胚胎和胚外组织经历从头DNA甲基化，从而建立整体DNA甲基化模式，并影响基因表达谱（Reik et al.，2001），并且最近的几项研究已经将修饰的DNA甲基化与胎盘形成期间特定基因的表达改变相关联（Nelissen et al.，2013; de Waal等人，2014; Sakian等人，2015年）的报告。此外，de Waal等人评估了胎盘形态和选定印迹基因印迹控制区的甲基化模式，以及E18中的总体DNA甲基化水平。5通过IVF产生的小鼠孕体（de Waal等人，
In vitro fertilization (IVF) is one of the most effective and successful assisted reproductive technologies. It is widely used to treat human infertility, and is also used for animal breeding and propagation. While IVF is generally considered a safe and successful technology, there are several IVF-associated safety concerns, such as pregnancy loss, preterm birth, lower birthweight and birth defects, and higher risk of age-related disorders, such as heart disease, diabetes, or hypertension (Bergh et al., 1999; Racowsky, 2002; Schieve et al., 2002; Klemetti et al., 2006; Ceelen et al., 2008; Reefhuis et al., 2009; Wen et al., 2012; Hansen et al., 2013; Servick, 2014).A number of fetal studies have indicated that the IVF process may disrupt a series of biological processes, including genetic information processing (Giritharan et al., 2007; Fernandez-Gonzalez et al., 2009; Driver et al., 2012), epigenetic modifications (Deshmukh et al., 2011; Oliver et al., 2012), amino acid and energy metabolism (Nie et al., 2013; Ren et al., 2015), and cytoskeleton organization (Tan et al., 2015). In addition, placental studies may be informative for a more comprehensive understanding of the underlying mechanisms in IVF-induced embryonic or offspring complications, as the placenta is known to play an important role in fetal development. The placenta provides the maternal-fetal interface and is essential for the exchange of gases, nutrients and waste products to support the developing fetus. It is also an important source of pregnancy-associated hormones and growth factors, and is involved in fetal immune tolerance (Rossant and Cross, 2001). Defective placentation and subsequent placental insufficiency can lead to maternal and fetal adverse pregnancy outcomes, and may also be associated with post-natal disease risks (Barker et al., 1990; Seckl and Holmes, 2007). Recent studies have indicated that IVF can alter placental development, affecting structure, size and transplacental nutrient transport ability (Delle Piane et al., 2010; Bloise et al., 2012; Haavaldsen et al., 2012; Tan et al., 2016). In addition, highthroughput gene expression and proteomic profiling studies can be useful for understanding the placental mechanisms implicated in IVF-associated complications (Fauque et al., 2010a; Sui et al., 2014). In human and mouse during post-implantation embryonic development, embryonic and extraembryonic tissues undergo de novo DNA methylation, thereby establishing a global DNA methylation pattern, and influencing gene expression profiles (Reik et al., 2001), and several recent investigations have associated modified DNA methylation with altered expression of specific genes during placentation (Nelissen et al., 2013; de Waal et al., 2014; Sakian et al., 2015). In addition, de Waal et al. assessed placental morphology and methylation patterns of imprinting control regions of select imprinted genes, as well as global DNA methylation levels in E18. 5 mouse concepti generated by IVF (de Waal et al.,