Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China.
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, 226001, China; Department of Obstetrics and Gynecology, The Second Hospital of Shanxi Medical University, 7, Taiyuan, 030001, China.
Mol Cell Endocrinol. 2023 Aug 20;574:111991. doi: 10.1016/j.mce.2023.111991. Epub 2023 Jun 17.
The mortality of preimplantation embryos is positively correlated with maternal age. However, the underlying mechanism for the poor quality of embryos remains unclear. Here, we found that aging caused elevated intracellular pH (pHi) in zygotes, which could trigger aberrant mitochondrial membrane potential, increased reactive oxygen species (ROS) levels, and poor embryo development. Moreover, single-cell transcriptome sequencing of mouse zygotes identified 120 genes that were significantly differentially expressed (DE) between young and older zygotes. These include genes such as Slc14a1, Fxyd5, CD74, and Bst, which are related to cell division, ion transporter, and cell differentiation. Further analysis indicated that these DE genes were enriched in apoptosis, the NF-kappa B signaling pathway, and the chemokine signaling pathway, which might be the key regulatory pathway affecting the quality of zygotes and subsequent embryo development. Taken together, our study helps elucidate the poor quality and development of older preimplantation embryos.
胚胎着床前胚胎的死亡率与母体年龄呈正相关。然而，胚胎质量差的潜在机制仍不清楚。在这里，我们发现衰老导致受精卵内 pH 值（pHi）升高，这可能引发异常的线粒体膜电位、增加活性氧（ROS）水平，并导致胚胎发育不良。此外，对小鼠受精卵的单细胞转录组测序鉴定出 120 个在年轻和年老受精卵之间差异表达（DE）的基因。这些基因包括 Slc14a1、Fxyd5、CD74 和 Bst 等，与细胞分裂、离子转运和细胞分化有关。进一步的分析表明，这些 DE 基因富集在细胞凋亡、NF-κB 信号通路和趋化因子信号通路中，这可能是影响受精卵质量和随后胚胎发育的关键调控通路。总之，我们的研究有助于阐明老年胚胎着床前胚胎质量差和发育不良的原因。
