Importin α7 deficiency causes infertility in male mice by disrupting spermatogenesis

Item Type:

Preprint

Title:

Creators Name:

Liu, N. and Qadri, F. and Busch, H. and Huegel, S. and Sihn, G. and Chuykin, I. and Hartmann, E. and Bader, M. and Rother, F.

Abstract:

Spermatogenesis is driven by an ordered series of events, which rely on trafficking of specific proteins between nucleus and cytoplasm. The importin α family of proteins mediates movement of specific cargo proteins when bound to importin β. Importin α 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 α7 in spermatogenesis and male fertility. We show that ablation of importin α7 in male mice leads to infertility and has multiple cumulative effects on both germ cells and Sertoli cells. Importin α7-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 α7 in spermatogenesis and hence in male fertility.

Keywords:

Importin, Karyopherin, Spermatogenesis, Male Fertility, Testis, Animals, Mice

Source:

bioRxiv

Publisher:

Cold Spring Harbor Laboratory Press

Article Number:

2020.11.09.374652

Date:

9 November 2020

Official Publication:

https://doi.org/10.1101/2020.11.09.374652

Related to:

URL	URL Type
https://edoc.mdc-berlin.de/20903/	Final version

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