Publication Date
1-17-2023
DOI
10.1172/JCI166279
PMID
36647833
PMCID
PMC9843045
PubMedCentral® Posted Date
1-17-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Pregnancy, Female, Humans, Animals, Mice, Active Transport, Cell Nucleus, Karyopherins, Mothers, Embryonic Development, Oocytes, Pregnancy Proteins, Ribosomal Proteins
Abstract
The genetic basis of preimplantation embryo arrest is slowly being unraveled. Recent discoveries point to maternally expressed proteins required for cellular functions before the embryonic genome is activated. In this issue of the JCI, Wang, Miyamoto, et al. suggest a critical role for karyopherin-mediated protein cargo transport between oocyte cytoplasm and nucleus. Defective maternal oocyte-expressed human karyopherin subunit α7 (KPNA7) and mouse KPNA2 fail to bind a critical substrate, ribosomal L1 domain-containing protein 1 (RSL1D1), affecting its transport to the nucleus. As shown in embryos of Kpna2-null females, the consequences are disrupted zygotic genome activation and arrest of development. These findings have important implications for diagnosis and treatment of female infertility.