大学共同利用機関法人自然科学研究機構 基礎生物学研究所生殖細胞研究部門・特任研究員淨住 大慈Daiji KiyozumiNational Institutes of Natural Sciences, National Institute for Basic BiologyAbstractSpermatozoa acquire fertilizing ability not during their formation in the testis but as they pass through the male reproductive tract, particularly the epididymis. However, the molecular mechanisms underlying this maturation process have remained largely unknown. In this study, lumicrine signaling—a testis-to-epididymis communication pathway mediated by the secreted factor NELL2—was investigated. A novel small secreted protein, NICOL, was identified as a cofactor that forms a ligand complex with NELL2 and is essential for sperm maturation and male fertility. Using knockout mouse models and transcriptomic profiling, distinct roles of endocrine and lumicrine signaling in regulating gene expression and epithelial differentiation in the epididymis were characterized. These findings elucidate how testicular signals modulate the epididymal environment to support sperm maturation and suggest that this mechanism has evolved in association with internal fertilization in vertebrates. The present study advances the understanding of male reproductive physiology and provides a basis for developing diagnostics and non-hormonal male contraceptives.はじめに生物が種を維持するためには生殖によって個体を新生しなければならない．人類にとっても子孫繁栄はいつの時代も大きな課題であり，現代においてもヒトでは子どもを持ちたいと思いつつなかなか妊娠に至らないカップルは決して少なくはなく 10 組に 1 組とも 5 組に 1 組ともいわれている．このようなヒトの不妊の具体的な原因はわからない場合が多いものの，過去の WHO の調査では不妊の原因のうち 24％が「男性のみ」，24％が「男女とも」に帰するという結果が報告されており 1），生殖や不妊における男性側因子の重要性が示唆されている．雄性配偶子である精子は精巣で作られるが，実は精巣で作られたばかりの精子にはまだ受精能力が― 40 ―生殖路による精子成熟の分子機構解明The…molecular…mechanisms…underlying…sperm…maturationin…the…reproductive…tract
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