Elevated intracellular pH of zygotes during mouse aging causes mitochondrial dysfunction associated with poor embryo development

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.