Woods Laura, Perez-Garcia Vicente, Kieckbusch Jens, Wang Xiaoqiu, DeMayo Francesco, Colucci Francesco, Hemberger Myriam
Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
Nat Commun. 2017 Sep 5;8(1):352. doi: 10.1038/s41467-017-00308-x.
Mammalian reproductive performance declines rapidly with advanced maternal age. This effect is largely attributed to the exponential increase in chromosome segregation errors in the oocyte with age. Yet many pregnancy complications and birth defects that become more frequent in older mothers, in both humans and mice, occur in the absence of karyotypic abnormalities. Here, we report that abnormal embryonic development in aged female mice is associated with severe placentation defects, which result from major deficits in the decidualisation response of the uterine stroma. This problem is rooted in a blunted hormonal responsiveness of the ageing uterus. Importantly, a young uterine environment can restore normal placental as well as embryonic development. Our data highlight the pivotal, albeit under-appreciated, impact of maternal age on uterine adaptability to pregnancy as major contributor to the decline in reproductive success in older females.Advanced maternal age has been associated with lower reproductive success and higher risk of pregnancy complications. Here the authors show that maternal ageing-related embryonic abnormalities in mouse are caused by decidualisation and placentation defects that can be rescued by transferring the embryo from an old to a young uterus.
哺乳动物的生殖能力会随着母体年龄的增长而迅速下降。这种影响很大程度上归因于随着年龄增长，卵母细胞中染色体分离错误呈指数级增加。然而，在人类和小鼠中，许多在老年母亲中更常见的妊娠并发症和出生缺陷，在没有核型异常的情况下也会出现。在这里，我们报告老年雌性小鼠的异常胚胎发育与严重的胎盘形成缺陷有关，这是由子宫基质蜕膜化反应的主要缺陷导致的。这个问题源于衰老子宫的激素反应迟钝。重要的是，年轻的子宫环境可以恢复正常的胎盘以及胚胎发育。我们的数据强调了母体年龄对子宫适应妊娠的关键影响，尽管这一影响未得到充分重视，它是老年雌性生殖成功率下降的主要原因。高龄产妇与较低的生殖成功率和较高的妊娠并发症风险相关。在这里，作者表明，小鼠中与母体衰老相关的胚胎异常是由蜕膜化和胎盘形成缺陷引起的，将胚胎从老龄子宫转移到年轻子宫可以挽救这些缺陷。
