Sperm microRNA Content Is Altered in a Mouse Model of Male Obesity, but the Same Suite of microRNAs Are Not Altered in Offspring's Sperm.
Sperm microRNA Content Is Altered in a Mouse Model of Male Obesity, but the Same Suite of microRNAs Are Not Altered in Offspring's Sperm.
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DOI：
10.1371/journal.pone.0166076
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Lane M
中科院分区：
文献类型：
--
作者：
Fullston T;Ohlsson-Teague EM;Print CG;Sandeman LY;Lane M
肥胖症的流行率在全世界都在增加，自1970年代以来，育龄男子的肥胖率增加了两倍。令人担忧的是，肥胖不仅与其他慢性疾病并存，而且越来越多的证据表明，它增加了儿童的非传染性疾病负担（例如死亡率，肥胖症，自闭症）。动物研究表明，父亲肥胖会增加后代代谢（如葡萄糖代谢缺陷、肥胖）和生殖障碍的风险。精子内的表观遗传变化是明确的机制候选者，与父亲的环境和后代表型的变化有关。具体来说，有新的证据表明，父亲精子中的microRNA含量既会对父亲的环境线索做出反应，也会改变基因表达谱和早期胚胎的后续发育。我们使用高脂饮食（HFD）诱导的肥胖小鼠模型来研究男性肥胖是否可以调节精子microRNA含量。我们还研究了父亲精子microRNA含量的这种改变是否会导致男性后代精子的类似变化。我们的研究最初由Taqman PCR阵列指导，该阵列指示HFD小鼠中28种精子携带的microRNA的差异丰度。在一个更大的建立者雄性队列中的qPCR确认表明，由于HFD喂养，这些microRNA中的13种差异丰富（11种上调; 2种下调）。尽管在通过雄性后代血统生育的孙子中也观察到代谢和生殖表型，但没有证据表明13种microRNA中的任何一种在雄性后代精子中也失调。这可能是由于在两组后代中观察到的变化，并表明其他机制可能在后代和孙子之间起作用。因此，13种精子携带的微小RNA受到父亲的HFD的调节，并且这种改变的微小RNA有效载荷在受精时转移到胚胎可能会改变受精后的胚胎分子组成，改变其生长轨迹，最终影响成年后代表型，并可能有助于父系编程。
The prevalence of obesity is increasing worldwide and has tripled in men of reproductive age since the 1970s. Concerningly, obesity is not only comorbid with other chronic diseases, but there is mounting evidence that it increases the non-communicable disease load in their children (eg mortality, obesity, autism). Animal studies have demonstrated that paternal obesity increases the risk of metabolic (eg glucose metabolism defects, obesity) and reproductive disorders in offspring. Epigenetic changes within sperm are clear mechanistic candidates that are associated with both changes to the father’s environment and offspring phenotype. Specifically there is emerging evidence that a father’s sperm microRNA content both responds to paternal environmental cues and alters the gene expression profile and subsequent development of the early embryo. We used a mouse model of high fat diet (HFD) induced obesity to investigate whether male obesity could modulate sperm microRNA content. We also investigated whether this alteration to a father’s sperm microRNA content lead to a similar change in the sperm of male offspring. Our investigations were initially guided by a Taqman PCR array, which indicated the differential abundance of 28 sperm borne microRNAs in HFD mice. qPCR confirmation in a much larger cohort of founder males demonstrated that 13 of these microRNAs were differentially abundant (11 up-regulated; 2 down-regulated) due to HFD feeding. Despite metabolic and reproductive phenotypes also being observed in grand-offspring fathered via the male offspring lineage, there was no evidence that any of the 13 microRNAs were also dysregulated in male offspring sperm. This was presumably due to the variation seen within both groups of offspring and suggests other mechanisms might act between offspring and grand-offspring. Thus 13 sperm borne microRNAs are modulated by a father’s HFD and the presumed transfer of this altered microRNA payload to the embryo at fertilisation potentially acts to alter the embryonic molecular makeup post-fertilisation, altering its growth trajectory, ultimately affecting adult offspring phenotype and may contribute to paternal programming.
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