ARRDC5 deficiency impairs spermatogenesis by affecting SUN5 and NDC1.

Development

Institute of Pediatrics, Children's Hospital of Fudan University, the Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China.

Published: December 2023

AI Article Synopsis

  • Sperm with proper shape and movement are crucial for fertilization, and the connection between the sperm head and tail is vital for their function.
  • The study found that a protein called ARRDC5 is important for sperm development, as mice lacking this protein had issues like bent sperm heads and reduced movement, leading to infertility.
  • Through mass spectrometry, researchers discovered that ARRDC5 interacts with proteins NDC1 and SUN5, which are involved in the sperm's attachment mechanisms, indicating that ARRDC5's role is vital for successful sperm function and potential therapeutic applications.

Article Abstract

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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Source
http://dx.doi.org/10.1242/dev.201959DOI Listing

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