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首页> 外文期刊>Environmental Epigenetics >Folic acid supplementation reduces multigenerational sperm miRNA perturbation induced by in utero environmental contaminant exposure
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Folic acid supplementation reduces multigenerational sperm miRNA perturbation induced by in utero environmental contaminant exposure

机译：叶酸补充剂减少子宫内环境污染物暴露引起的多代精子miRNA扰动

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Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here, we report that folic acid (FA) supplementation mitigates sperm miRNA profiles transgenerationally following in utero paternal exposure to POPs in a rat model. Pregnant founder dams were exposed to an environmentally relevant POPs mixture (or corn oil) ± FA supplementation and subsequent F1–F4 male descendants were not exposed to POPs and were fed the FA control diet. Sperm miRNA profiles of intergenerational (F1, F2) and transgenerational (F3, F4) lineages were investigated using miRNA deep sequencing. Across the F1–F4 generations, sperm miRNA profiles were less perturbed with POPs+FA compared to sperm from descendants of dams treated with POPs alone. POPs exposure consistently led to alteration of three sperm miRNAs across two generations, and similarly one sperm miRNA due to POPs+FA; which was in common with one POPs intergenerationally altered sperm miRNA. The sperm miRNAs that were affected by POPs alone are known to target genes involved in mammary gland and embryonic organ development in F1, sex differentiation and reproductive system development in F2 and cognition and brain development in F3. When the POPs treatment was combined with FA supplementation, however, these same miRNA-targeted gene pathways were perturbed to a lesser extend and only in F1 sperm. These findings suggest that FA partially mitigates the effect of POPs on paternally derived miRNA in a intergenerational manner.
机译：持久性有机污染物（POPs）可以诱导父系种系的表观遗传变化。在这里，我们报告说，叶酸（FA）补充可减轻子宫内父本暴露于POP中的大鼠模型中的精子miRNA谱系。怀孕的始祖大坝暴露于与环境有关的持久性有机污染物混合物（或玉米油）±FA补充剂，随后的F1-F4雄性后代不暴露于POPs，并接受FA对照饮食。使用miRNA深度测序研究了世代（F1，F2）和跨世代（F3，F4）世代的精子miRNA谱。在整个F1-F4代中，与仅用POPs处理的水坝后代的精子相比，POPs + FA对精子miRNA的干扰较小。持久性有机污染物的暴露持续导致两代中三个精子miRNA的改变，同样地，由于持久性有机污染物+脂肪酸，一个精子miRNA发生了变化。这与一种POPs世代改变的精子miRNA相同。已知仅受POPs影响的精子miRNA靶向F1的乳腺和胚胎器官发育，F2的性别分化和生殖系统发育以及F3的认知和脑发育相关基因。然而，当POPs处理与FA补充剂结合使用时，这些相同的miRNA靶向基因途径受到的干扰较小，仅在F1精子中。这些发现表明，FA以世代相传的方式部分缓解了POPs对父源miRNA的影响。

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