Testicular origin of epigenetic inheritance independent of sperm mitochondrial DNA and epididymal exposure

• 成果类型: Article
• 署名作者: Wang, Zhuqing; Yamauchi, Yasuhiro; Chen, Sheng; Zheng, Huili; Ward, Monika A.; Yan, Wei
• 署名单位: Washington State University; University of California System; University of California Los Angeles; University of Hawaii System; University of California System; University of California Los Angeles; David Geffen School of Medicine at UCLA; University of California Los Angeles Medical Center
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2611096123
• 发表日期: 2026-06-16
• 页码: e2611096123
• 关键词: epigenetic inheritance; sperm epigenome; mitochondrial DNA; small RNA; rnas

摘要

Paternal epigenetic inheritance remains mechanistically unresolved. Recent studies propose that environmental exposures induce mitochondrial DNA (mtDNA)-dependent transcription in sperm during epididymal transit, altering small RNA content and offspring phenotypes. Here, we show that mature murine sperm are effectively devoid of mtDNA, precluding mtDNA-dependent transcription, and that sperm-borne mitochondrial RNAs originate during spermatogenesis. Testicular sperm transmitted diet-induced metabolic traits as efficiently as, and in most cohorts more efficiently than, epididymal sperm. These findings establish testicular inheritance independent of sperm mtDNA transcription and epididymal exposure.