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Publication : ARRDC5 deficiency impairs spermatogenesis by affecting SUN5 and NDC1.

First Author  Liu R Year  2023
Journal  Development Volume  150
Issue  24 PubMed ID  37997706
Mgi Jnum  J:343794 Mgi Id  MGI:7570248
Doi  10.1242/dev.201959 Citation  Liu R, et al. (2023) ARRDC5 deficiency impairs spermatogenesis by affecting SUN5 and NDC1. Development 150(24):dev201959
abstractText  Sperm with normal morphology and motility are essential for successful fertilization, and the strong attachment of the sperm head-tail coupling apparatus to the nuclear envelope during spermatogenesis is required to ensure the integrity of sperm for capacitation and fertilization. Here, we report that Arrdc5 is associated with spermatogenesis. The Arrdc5 knockout mouse model showed male infertility characterized by a high bent-head rate and reduced motility in sperm, which led to capacitation defects and subsequent fertilization failure. Through mass spectrometry, we found that ARRDC5 affects spermatogenesis by affecting NDC1 and SUN5. We further found that ARRDC5 might affect the vesicle-trafficking protein SEC22A-mediated transport and localization of NDC1, SUN5 and other head-tail coupling apparatus-related proteins that are responsible for initiating the attachment of the sperm head and tail. We finally performed intracytoplasmic sperm injection as a way to explore therapeutic strategies. Our findings demonstrate the essential role and the underlying molecular mechanism of ARRDC5 in anchoring the sperm head to the tail during spermatogenesis.
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