男性不妊の謎を解く(Unraveling the Mysteries of Male Infertility)

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2025-03-05 ラトガース大学

ルトガース大学の研究者は、男性不妊症の原因解明に向けて、精子形成に関与する新たな遺伝子や分子メカニズムを特定した。不妊の多くは原因不明とされているが、本研究により遺伝的要因が重要な役割を果たすことが示唆された。この発見は、より正確な診断法の開発や、新たな不妊治療法の確立につながる可能性がある。今後の研究により、個別化医療の実現が期待されている。

<関連情報>

トランスポゾンの抑制と雄性生殖細胞系列の減数分裂に細胞間ブリッジが必須である Intercellular bridges are essential for transposon repression and meiosis in the male germline

Julia Sorkin,Kevin Tilton,Matthew A. Lawlor,Shreya N. Sarathy,Shun Liang,Angelina Albanese,Mashiat Rabbani,Saher S. Hammoud,Christopher E. Ellison,Florencia Pratto & Devanshi Jain
Nature Communications  Published:10 February 2025
DOI:https://doi.org/10.1038/s41467-025-56742-9

男性不妊の謎を解く(Unraveling the Mysteries of Male Infertility)

Abstract

Germ cell connectivity via intercellular bridges is a widely conserved feature across metazoans. However, its functional significance is poorly understood. Intercellular bridges are essential for fertility in male mice as genetic ablation of a critical bridge component, TEX14, causes spermatogenic failure, but the underlying reasons are unknown. Here we utilized a Tex14 hypomorph with reduced intercellular bridges along with Tex14-null mice that completely lack bridges to examine the roles of germ cell connectivity during spermatogenesis. We report that in males deficient for TEX14 and intercellular bridges, germ cells fail to complete meiotic DNA replication, synapsis and meiotic double-strand break repair. They also derepress retrotransposons and accumulate retrotransposon-encoded proteins during meiosis. Single-cell RNA-sequencing confirms sharing of transcripts between wild-type spermatids and demonstrates its partial attenuation in Tex14 hypomorphs, indicating that intercellular bridges enable cytoplasmic exchange between connected germ cells in testes. Our findings suggest that regulation of meiosis is non-cell-intrinsic and inform a model in which intercellular bridges influence critical meiotic events and protect germline genome integrity during spermatogenesis.

医療・健康
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