Macrophage ubiquitin-specific protease 2 contributes to motility, hyperactivation, capacitation, and in vitro fertilization activity of mouse sperm

Mayuko Hashimoto, Shunsuke Kimura, Chihiro Kanno, Yojiro Yanagawa, Takafumi Watanabe, Jun Okabe, Eiki Takahashi, Masashi Nagano, Hiroshi Kitamura

研究成果: Article査読

抄録

Macrophages are innate immune cells that contribute to classical immune functions and tissue homeostasis. Ubiquitin-specific protease 2 (USP2) controls cytokine production in macrophages, but its organ-specific roles are still unknown. In this study, we generated myeloid-selective Usp2 knockout (msUsp2KO) mice and specifically explored the roles of testicular macrophage-derived USP2 in reproduction. The msUsp2KO mice exhibited normal macrophage characteristics in various tissues. In the testis, macrophage Usp2 deficiency negligibly affected testicular macrophage subpopulations, spermatogenesis, and testicular organogenesis. However, frozen–thawed sperm derived from msUsp2KO mice exhibited reduced motility, capacitation, and hyperactivation. In addition, macrophage Usp2 ablation led to a decrease in the sperm population exhibiting high intracellular pH, calcium influx, and mitochondrial membrane potential. Interrupted pronuclei formation in eggs was observed when using frozen–thawed sperm from msUsp2KO mice for in vitro fertilization. Administration of granulocyte macrophage-colony stimulating factor (GM-CSF), whose expression was decreased in testicular macrophages derived from msUsp2KO mice, restored mitochondrial membrane potential and total sperm motility. Our observations demonstrate a distinct role of the deubiquitinating enzyme in organ-specific macrophages that directly affect sperm function.

本文言語English
ページ(範囲)2929-2948
ページ数20
ジャーナルCellular and Molecular Life Sciences
78
6
DOI
出版ステータスPublished - 2021 3

ASJC Scopus subject areas

  • 分子医療
  • 分子生物学
  • 薬理学
  • 細胞および分子神経科学
  • 細胞生物学

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