Oveisi Anahita, Vahdati Akbar, Shahhoseini Maryam, Favaedi Raha, Maroufizadeh Saman, Movaghar Bahar
Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran.
Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
Cell J. 2021 Apr;23(1):99-108. doi: 10.22074/cellj.2021.6953. Epub 2021 Mar 1.
Genomic imprinting is an epigenetic phenomenon that plays a critical role in normal development of embryo. Using exogenous hormones during assisted reproductive technology (ART) can change an organism hormonal profile and subsequently affect epigenetic events. Ovarian stimulation changes gene expression and epigenetic pattern of imprinted genes in the organs of mouse fetus.
For this experimental study, expression of three imprinted genes (Insulin-like growth factor 2) and (Cyclin-dependent kinase inhibitor 1C), which have important roles in development of placenta and embryo, and the epigenetic profile of their regulatory region in some tissues of 19-days-old female fetuses, from female mice subjected to ovarian stimulation, were evaluated by quantitative reverse-transcription PCR (qRT-PCR) and Chromatin immunoprecipitation (ChIP) methods.
gene was significantly lower in heart (P<0.05), liver (P<0.05), lung (P<0.01), placenta (P<0.01) and ovary (P<0.01). It was significantly higher in kidney of ovarian stimulation group compared to control fetuses (P<0.05). expression was significantly higher in brain (P<0.05) and kidney (P<0.05), while it was significantly lower in lung of experimental group fetuses in comparison with control fetuses (P<0.05). expression was significantly higher in lung (P<0.05). It was significantly decreased in placenta of experimental group fetuses rather than the control fetuses (P<0.05). Histone modification data and DNA methylation data were in accordance to the gene expression profiles.
Results showed altered gene expressions in line with changes in epigenetic pattern of their promoters in the ovarian stimulation group, compared to normal cycle.
基因组印记是一种表观遗传现象,在胚胎的正常发育中起关键作用。在辅助生殖技术(ART)过程中使用外源激素会改变机体的激素水平,进而影响表观遗传事件。卵巢刺激会改变小鼠胎儿器官中印迹基因的基因表达和表观遗传模式。
在本实验研究中,通过定量逆转录PCR(qRT-PCR)和染色质免疫沉淀(ChIP)方法,评估了在接受卵巢刺激的雌性小鼠所产19日龄雌性胎儿的某些组织中,对胎盘和胚胎发育具有重要作用的三个印记基因(胰岛素样生长因子2)和(细胞周期蛋白依赖性激酶抑制剂1C)的表达及其调控区域的表观遗传特征。
基因在心脏(P<0.05)、肝脏(P<0.05)、肺(P<0.01)、胎盘(P<0.01)和卵巢(P<0.01)中显著降低。与对照胎儿相比,卵巢刺激组胎儿的肾脏中该基因显著升高(P<0.05)。基因表达在大脑(P<0.05)和肾脏(P<0.05)中显著升高,而与对照胎儿相比,实验组胎儿的肺中该基因显著降低(P<0.05)。基因表达在肺中显著升高(P<0.05)。与对照胎儿相比,实验组胎儿的胎盘中该基因显著降低(P<0.05)。组蛋白修饰数据和DNA甲基化数据与基因表达谱一致。
结果表明,与正常周期相比,卵巢刺激组中基因表达的改变与其启动子表观遗传模式的变化一致。