Epigenetic inheritance of paternally expressed imprinted genes in the testes of ICSI mice.
Epigenetic inheritance of paternally expressed imprinted genes in the testes of ICSI mice.
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ICSI 小鼠睾丸中父系表达的印记基因的表观遗传。
DOI：
10.2174/13816128113199990520
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发表时间：
2014-03
影响因子：
3.1
通讯作者：
Liu, Xiao-Zhen
中科院分区：
文献类型：
--
作者：
Jin, Fan;Fu, Rongguo;Wang, Li-Ya;Wang, Ning;Zhang, Fan;Le, Fang;Li, Lei;Li, Le-Jun;Liu, Xiao-Zhen
通过卵胞浆内单精子注射（ICSI）或其他辅助生殖技术（ART）出生的男性的生殖健康状况更差已在许多研究中报道。然而，由于遗传和环境因素的干扰，很难确定ICSI方法是否会影响男性生殖健康。因此，本研究建立了ART小鼠模型。除精液质量、血清睾酮和睾丸组织学检查外，还检测了6个父系印迹基因在成年F1和F2代小鼠睾丸中的表达和甲基化水平。ICSI组Kcnq1ot1、Mest、Peg3、Plagl1和Snrpn的表达均低于自然受孕组（NC），但未发现表型异常。体外受精（IVF）小鼠Kcnq1ot1、Peg3和Snrpn的表达低于控制性超排卵（COH）小鼠，但高于ICSI小鼠。NC组与ICSI组之间、IVF组与ICSI组之间的差异也主要表现在F2代。在甲基化分析中，无论对照组之间是否存在显著差异，甲基化水平的变化趋势几乎与其对应的基因表达相反。这些结果表明，ICSI小鼠睾丸中存在父系表达基因的差异表达，这种差异表达可能是由甲基化修饰介导的。ICSI和机械刺激均可引起表观遗传学改变的代际传递。体外培养和机械刺激是导致睾丸中父系印迹基因表达下调的主要因素。
Worse reproductive health in the men born through intracytoplasmic sperm injection (ICSI) or other assisted reproductive techniques (ART) has been reported in many studies. However, owing to the interference of genetic and environmental factors, it is difficult to identify whether ICSI method would affect male reproductive health. Therefore, ART mouse models were established in this study. Besides semen quality, serum testosterone and histological analysis of testes, 6 paternally expressed imprinted genes were chosen to detect their expressions and methylation levels in testes of adult F1 and F2 mice. Although the phenotypic abnormalities weren't found, Kcnq1ot1, Mest, Peg3, Plagl1 and Snrpn in ICSI group showed lower expressions than those in naturally conceived (NC) group. The expressions of Kcnq1ot1, Peg3 and Snrpn in in vitro fertilization (IVF) conceived mice was lower than those in controlled ovarian hyperstimulation (COH) conceived mice, but higher than those in ICSI mice. Most differences between NC and ICSI group and between IVF and ICSI group were also represented in F2 generations. During the methylation analysis, no matter there was significant difference between compared groups, the changing trends of methylation level were almost opposite to their corresponding gene expressions. These results indicated that the differential expressions of paternally expressed genes occurred in testes of ICSI mice, which may be mediated by methylation modification. Both ICSI procedure and mechanical stimulation can induce intergenerational transmission of the epigenetic changes. In vitro culture and mechanical stimulation were the main factors inducing the down regulation of paternally expressed imprinted genes in testes.