Sharma Abhay
CSIR-Institute of Genomics and Integrative Biology, Council of Scientific and Industrial Research, Sukhdev Vihar, Mathura Road, New Delhi 110025, India.
Environ Epigenet. 2015 Oct 20;1(1):dvv005. doi: 10.1093/eep/dvv005. eCollection 2015.
Transgenerational epigenetic inheritance in mammals has been controversial due to inherent difficulties in its experimental demonstration. A recent report has, however, opened a new front in the ongoing debate by claiming that endocrine disrupting chemicals, contrary to previous findings, do not cause effects across generations. This claim is based on the observation that gene expression changes induced by these chemicals in the exposed and unexposed generations are mainly in the opposite direction. This analysis shows that the pattern of gene expression reported in the two generations is not expected by chance and is suggestive of transmission across generations. A meta-analysis of diverse data sets related to endocrine disruptor-induced transgenerational gene expression alterations, including the data provided in the said report, further suggests that effects of endocrine disrupting chemicals persist in unexposed generations. Based on the prior evidence of phenotypic variability and gene expression alterations in opposite direction between generations, it is argued here that calling evidence of mismatched directionality in gene expression in experiments testing potential of environmental agents in inducing epigenetic inheritance of phenotypic traits as negative is untenable. This is expected to settle the newly raised doubts over epigenetic inheritance in mammals.
由于哺乳动物中跨代表观遗传继承在实验证明方面存在固有困难，一直颇具争议。然而，最近一份报告在当前的争论中开辟了一个新的阵线，声称与之前的研究结果相反，内分泌干扰化学物质不会导致跨代效应。这一说法基于这样的观察，即这些化学物质在暴露和未暴露代中诱导的基因表达变化主要是相反的方向。该分析表明，两代中报告的基因表达模式并非偶然出现，而是暗示了跨代传递。对与内分泌干扰物诱导的跨代基因表达改变相关的各种数据集进行的荟萃分析，包括上述报告中提供的数据，进一步表明内分泌干扰化学物质的影响在未暴露代中持续存在。基于之前关于两代之间表型变异性和基因表达改变方向相反的证据，本文认为，在测试环境因素诱导表型性状表观遗传继承潜力的实验中，将基因表达方向不匹配的证据称为负面证据是站不住脚的。这有望解决最近对哺乳动物表观遗传继承新出现的疑虑。
