Transgenerational Developmental Programming of Ovarian Reserve
Transgenerational Developmental Programming of Ovarian Reserve
复制标题
DOI：
10.1038/srep16175
复制
发表时间：
2015-11-03
影响因子：
4.6
通讯作者：
Ozanne, S. E.
中科院分区：
文献类型：
--
作者：
Aiken, C. E.;Tarry-Adkins, J. L.;Ozanne, S. E.
暴露于不利的早期生活环境会导致长期的健康问题，其中许多问题会在后代身上重演。女性生殖道对早期生命的影响特别敏感，在孕体的发育过程中起着关键作用。我们研究了次优的祖母饮食对孙女生殖潜力的影响，在没有任何进一步的饮食操作的女儿在大鼠低蛋白饮食模型。暴露于低蛋白的祖母-母亲饮食导致卵巢储备减少和孙女腹内脂肪量增加，伴随着卵巢中氧化应激和mtDNA拷贝数不稳定性的加速积累。卵巢端粒长度在暴露的孙女中下降得更快，表明生殖道加速老化。因此，我们证明，次优的祖母在怀孕期间的饮食加速了后代的生殖老化。这些发现对于理解生育率随年龄下降的个体比率以及当前全球推迟生育趋势的临床影响具有重要意义。
Exposure to an adverse early-life environment leads to long-term health problems, many of which are recapitulated in subsequent generations. The female reproductive tract is particularly sensitive to early-life influences, and plays a pivotal role in programming the conceptus. We examine the influence of suboptimal grandmaternal diet on reproductive potential of granddaughters in the absence of any further dietary manipulations in the daughters in a rat low-protein diet model. Exposure to low-protein grand-maternal diet leads to decreased ovarian reserve and increased intra-abdominal fat mass in granddaughters, accompanied by accelerated accumulation of oxidative stress and mtDNA copy number instability in the ovaries. Ovarian telomere length declines more rapidly in the exposed granddaughters, indicating accelerated ageing in the reproductive tract. Thus, we demonstrate that suboptimal grandmaternal diet during pregnancy accelerates reproductive ageing across subsequent generations. These findings have important implications for understanding both individual rates of decline in fertility with age, and the clinical impact of current global trends towards delayed childbearing.