State Key Laboratory of Reproductive Medicine and Offspring Health, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Nanjing, 211166, China.
Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Adv Sci (Weinh). 2024 Aug;11(30):e2309184. doi: 10.1002/advs.202309184. Epub 2024 Jun 13.
It has been widely reported that obesity adversely impacts reproductive performance of females. However, the effects of maternal obesity on fetal germ cells remain poorly understood. In the present study, by employing a high-fat diet (HFD)-based mouse model, it is discovered that maternal obesity disrupts the chromosomal synapsis and homologous recombination during fetal oogenesis. Moreover, transcriptomic profiling reveales the potential molecular network controlling this process. Of note, the global hypermethylation of genomic DNA in fetal oocytes from obese mouse is detected. Importantly, time-restricted feeding (TRF) of obese mice not only ameliorate the meiotic defects, but also partly restore the epigenetic remodeling in fetal oocytes. In sum, the evidence are provided showing the deficit fetal oogenesis in obese mother, implicating a mechanism underlying the intergenerational effects of environmental insults. TRF may represent a potentially effective approach for mitigating fertility issues in obese patients.
已有大量报道表明肥胖会对女性的生殖功能产生不良影响。然而，母体肥胖对胎儿生殖细胞的影响仍知之甚少。在本研究中，通过采用高脂肪饮食（HFD）诱导的小鼠模型，研究人员发现母体肥胖会破坏胎儿卵母细胞发生过程中的染色体联会和同源重组。此外，转录组分析揭示了控制这一过程的潜在分子网络。值得注意的是，还检测到肥胖小鼠的胎儿卵母细胞中基因组 DNA 的整体超甲基化。重要的是，对肥胖小鼠进行限时喂养（TRF）不仅可以改善减数分裂缺陷，还可以部分恢复胎儿卵母细胞中的表观遗传重塑。总之，本研究提供了肥胖母亲胎儿卵母细胞发生缺陷的证据，提示了环境因素对代际影响的机制。限时喂养可能是一种减轻肥胖患者生育问题的潜在有效方法。
