Effect of paternal resveratrol intake on mitochondria and telomere length in mouse embryos and offspring

Apr 5, 2026The Journal of reproduction and development

Father’s resveratrol intake linked to changes in energy units and chromosome tips in mouse embryos and offspring

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Abstract

Paternal resveratrol intake may modulate embryonic development and offspring characteristics.

In offspring of aged fathers, mitochondrial DNA copy number and telomere length in heart tissue were altered in a sex-dependent manner.
Sperm from older males showed telomere length elongation with continuous resveratrol administration.
Resveratrol treatment significantly increased mitochondrial DNA copy number and reduced lipid content in blastocysts from young female oocytes.
The preincubation of sperm from young untreated males in fluid from resveratrol-treated males reduced lipid content in blastocysts but did not affect mitochondrial DNA copy number or telomere length.
Resveratrol intake is associated with changes in metabolic pathways, including lipid metabolism, as revealed by RNA-sequencing.

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Advanced paternal age affects embryonic development and offspring phenotypes. We previously demonstrated that resveratrol prevents age-associated declines in the mitochondrial DNA copy number (mt-cn) and telomere length (TL) in embryos. The present study was performed to investigate the effects of paternal resveratrol intake on the mt-cn and TL in pups and embryos produced either via in vitro fertilization (IVF) or IVF using sperm preincubated in epididymal fluid (EF). C57BL/6N male mice were administered drinking water containing either the vehicle (ethanol, 1/2500) or 0.1 mM resveratrol. When these males were mated with young ICR females, paternal resveratrol treatment did not affect the mt-cn or TL in offspring derived from young fathers (16-25 weeks of age). In contrast, in offspring of aged fathers (41-51 weeks of age), the mt-cn and TL in heart tissue were altered in a sex-dependent manner. Moreover, continuous resveratrol administration to males until an advanced paternal age resulted in sperm TL elongation. However, resveratrol treatment did not affect the TL in embryos but significantly increased the mt-cn and reduced the lipid content in blastocysts produced via IVF using oocytes from young females (4 weeks of age). RNA- sequencing revealed that resveratrol treatment affected metabolic pathways, including lipid metabolism. The preincubation of sperm from young untreated males (11 weeks of age) in EF derived from resveratrol-treated males did not affect the mt-cn or TL in blastocysts but reduced the lipid content. In conclusion, paternal resveratrol intake modulates embryonic and offspring phenotypes, potentially through alterations in sperm TL, sperm epigenetic modifications, and bioactive components in EF. Resveratrol intake may exert long-term effects on offspring.

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Effect of paternal resveratrol intake on mitochondria and telomere length in mouse embryos and offspring

Abstract

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