4.4 Article

Male SIRT1 insufficiency leads to sperm with decreased ability to hyperactivate and fertilize

Journal

REPRODUCTION IN DOMESTIC ANIMALS
Volume 57, Issue -, Pages 72-77

Publisher

WILEY
DOI: 10.1111/rda.14172

Keywords

hyperactivated motility; infertility; SIRT1; sperm capacitation

Funding

  1. Charles University Research Fund [Q39]
  2. Ministry of Education, Youth and Sports of the Czech Republic [CZ.02.1.01/0.0/0.0/16_019/0 000787, 260 536]

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Deficiency of the SIRT1 protein plays a significant role in the acquisition of hyperactivated motility during capacitation. Sirt1(+/-) males exhibit mitochondrial injury and motility defects, leading to decreased fertilization rate. Therefore, Sirt1(+/-) males can serve as a model for studying age-related infertility.
Deficient sperm motility is a frequent cause of the age-related male sub-/infertility. Since the protein sirtuin 1 (SIRT1) develops anti-aging action and participates in sperm motility and ATP synthesis in mitochondria, we investigated its role in the acquisition of hyperactivated motility during capacitation. For this, the dynamics of sperm subpopulations were studied, using males of Sirt1(+/-) heterozygous mutant mice. After 2 hr of capacitation, we observed reduced percentage of hyperactivated spermatozoa in Sirt1(+/-) males. Interestingly, prior to capacitation, Sirt1(+/-) spermatozoa showed higher mitochondrial superoxide levels, which could render mitochondrial injury and thereby motility defects. Accordingly, the fertilization rate of Sirt1(+/-) males after mating was decreased. We elucidated that SIRT1 male insufficiency underlies posterior sperm defects to hyperactivate during capacitation and propose Sirt1(+/-) males as a model for the study of the age-related infertility.

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