Huegel, S. | bioRxiv Science

bioRxiv2023

Karyopherin α2 is a maternal effect gene required for early embryonic development and female fertility in mice

The nuclear transport of proteins plays an important role in mediating the transition from egg to embryo and distinct karyopherins have been implicated in this process. Here, we studied the impact of KPNA2 deficiency on preimplantation embryo development in mice. Loss of KPNA2 results in complete arrest at the 2cell stage and embryos exhibit the inability to activate their embryonic genome as well as a severely disturbed nuclear translocation of Nucleoplasmin 2. Our findings define KPNA2 as a new maternal effect gene.

developmental biology↗

bioRxiv2020

Importin α7 deficiency causes infertility in male mice by disrupting spermatogenesis

Spermatogenesis is driven by an ordered series of events, which rely on trafficking of specific proteins between nucleus and cytoplasm. The importin family of proteins mediates movement of specific cargo proteins when bound to importin {beta}. Importin genes have distinct expression patterns in mouse testis, implying they may have unique roles during mammalian spermatogenesis. Here we use a loss-of-function approach to specifically determine the role of importin 7 in spermatogenesis and male fertility. We show that ablation of importin 7 in male mice leads to infertility and has multiple cumulative effects on both germ cells and Sertoli cells. Importin 7-deficient mice exhibit an impaired Sertoli cell function, including loss of Sertoli cells and a compromised nuclear transport of the androgen receptor. Furthermore, our data demonstrate devastating defects in spermiogenesis that are accompanied by disturbed histone-protamine-exchange, absence of the transcriptional regulator Brwd1 and altered expression of Rfx2 target genes, resulting in incomplete sperm maturation and massive loss of sperms. Our work uncovers the essential role of importin 7 in spermatogenesis and hence in male fertility.

developmental biology↗