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

Proceedings of the National Academy of Sciences 2026 Open access

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Authors: Zhuqing Wang, Yasuhiro Yamauchi, Sheng Chen, Huili Zheng, Monika A. Ward, Wei Yan
DOI: 10.1073/pnas.2611096123
Cited by: 1
References: 15

Abstract

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.

Fields of Study & Subjects

Mitochondrial Function and Pathology Sperm and Testicular Function Epigenetics and DNA Methylation

Publication details

Journal / source
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Volume
123
Issue
24
Pages
e2611096123–e2611096123
Publication date
10 June 2026
Language
EN