SIRT7 links H3K36ac epigenetic regulation with genome maintenance in the aging mouse testis

Guitart-Solanes, A.; Romero, M.; Fernanadez-Duran, I.; Niedenberger, B. A.; Madrid-Sandin, C.; Roig, I.; Geyer, C. B.; Vaquero, A.; Schindler, K.; Vazquez, B. N.

doi:10.1101/2025.03.31.645534

bioRxiv · 10.1101/2025.03.31.645534

SIRT7 links H3K36ac epigenetic regulation with genome maintenance in the aging mouse testis

Guitart-Solanes, A.·Romero, M.·Fernanadez-Duran, I.·Niedenberger, B. A.·Madrid-Sandin, C.·Roig, I.·Geyer, C. B.·Vaquero, A.·Schindler, K.·Vazquez, B. N.

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Abstract

ABSTRACT/SUMMARYReproductive aging is an increasing health concern affecting family planning and overall well-being. While extensively studied in females, the mechanisms driving male reproductive aging remain largely unexamined. Here we found that mammalian Sirtuin 7 (SIRT7) sustains spermatogenesis in an age-dependent manner through the control of histone 3 lysine 36 acetylation (H3K36ac). SIRT7 deficiency in mice resulted in increased levels of H3K36ac in spermatogonia and spermatocytes. In a germ cell line, SIRT7 deficiency disrupted nucleosome stability and increased vulnerability to genotoxic stress. Importantly, undifferentiated spermatogonia, which are required for continuous sperm production, decreased prematurely in Sirt7-/- mice and showed genome damage accumulation. These changes were concurrent with age-dependent defects in homologous chromosome synapsis and partial meiotic arrest. Taken together, our results indicate that SIRT7 connects H3K36ac epigenetic regulation to long-term genome stability in male germ cells, ensuring steady-state spermatogenesis during the lengthy male reproductive lifespan.

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Guitart-Solanes, A., Romero, M., Fernanadez-Duran, I., Niedenberger, B. A., Madrid-Sandin, C., Roig, I., Geyer, C. B., Vaquero, A., Schindler, K., Vazquez, B. N.. 2025-04-01. SIRT7 links H3K36ac epigenetic regulation with genome maintenance in the aging mouse testis. https://doi.org/10.1101/2025.03.31.645534

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