1University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Level 4, Box 289, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Hills Rd., Cambridge, CB2 OQQ, UK.
FASEB J. 2013 Oct;27(10):3959-65. doi: 10.1096/fj.13-234484. Epub 2013 Jun 21.
Early life exposure to adverse environments can lead to a variety of metabolic and cardiovascular diseases in offspring. We hypothesize that female reproductive function may also be affected, with subsequent implications for fertility. We used an established maternal low-protein model where animals are born small but undergo rapid postnatal catch-up growth by suckling a control-fed dam (recuperated offspring). Markers of oxidative stress and cellular aging in reproductive tract tissues were assessed at 3 and 6 mo of age. Recuperated offspring had lower birth weight than controls (P<0.01) but caught up during lactation. 4-Hydroxynonenal (4HNE; an indicator of oxidative stress) was increased in recuperated animals compared with controls in both ovaries and oviducts at 6 mo. At 3 and 6 mo, ovaries and oviducts of recuperated offspring had increased mitochondrial (mt)DNA copy number (P<0.01). By contrast, germ-line cells showed no difference in mtDNA copy number, suggesting they were protected from suboptimal maternal nutrition. Oviduct and somatic ovarian telomere length declined more rapidly with age in recuperated animals. This accelerated cellular aging was associated with a declined ovarian reserve in developmentally programmed animals. These findings have significant clinical implications in light of worldwide trends to delayed childbearing.
早期生活中暴露于不利环境会导致后代出现多种代谢和心血管疾病。我们假设女性生殖功能也可能受到影响，从而对生育能力产生后续影响。我们使用了一种已建立的母体低蛋白模型，其中动物出生时较小，但通过吮吸控制喂养的母鼠（恢复的后代）进行快速的产后追赶生长。在 3 个月和 6 个月大时，评估生殖道组织中的氧化应激和细胞衰老标志物。与对照组相比，恢复组的后代出生体重较低（P<0.01），但在哺乳期赶上。与对照组相比，6 个月时恢复组的卵巢和输卵管中的 4-羟基壬烯（4HNE；氧化应激的指标）增加。在 3 个月和 6 个月时，恢复组的卵巢和输卵管的线粒体（mt）DNA 拷贝数增加（P<0.01）。相比之下，生殖细胞的 mtDNA 拷贝数没有差异，表明它们免受了母体营养不足的影响。恢复组的输卵管和卵巢体细胞端粒长度随年龄的增长下降更快。这种加速的细胞衰老与发育编程动物的卵巢储备减少有关。鉴于全球生育年龄推迟的趋势，这些发现具有重要的临床意义。
