ArticleReproductive sciences (Thousand Oaks, Calif.)2020
Declining BRCA-Mediated DNA Repair in Sperm Aging and its Prevention by Sphingosine-1-Phosphate.
Article in Reproductive sciences (Thousand Oaks, Calif.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- Perspective in the Mechanisms for Repairing Sperm DNA Damage.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Male aging in germ cells: What are we inheriting?Genetics and molecular biology · 2025Article
- Assessment of inbreeding coefficients and inbreeding depression on complex traits from genomic and pedigree data in Nelore cattle.BMC genomics · 2024Article
- The role of declining ataxia-telangiectasia-mutated (ATM) function in oocyte aging.Cell death discovery · 2024Article
- Research progress on the prevention and treatment of chemotherapy-induced ovarian damage.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Investigating the impact of paternal aging on murine sperm miRNA profiles and their potential link to autism spectrum disorder.Scientific reports · 2023Article
- Epimedium protects against dyszoospermia in mice with Pex3 knockout by exerting antioxidant effects and regulating the expression level of P16.Cell death & disease · 2022Article
- Sperm Lipid Markers of Male Fertility in Mammals.International journal of molecular sciences · 2021Review
- Unraveling the mechanisms of chemotherapy-induced damage to human primordial follicle reserve: road to developing therapeutics for fertility preservation and reversing ovarian aging.Molecular human reproduction · 2020Article
- DNA damage control then and now: a matter of life or death.Journal of assisted reproduction and genetics · 2020Article
- BRCA-related ATM-mediated DNA double-strand break repair and ovarian aging.Human reproduction update · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Recent data suggest that paternal age can have major impact on reproductive outcomes, and with increased age, there is increased likelihood of chromosomal abnormalities in the sperm. Here, we studied DNA damage and repair as a function of male aging and assessed whether sphingosine-1-phosphate (S1P), a ceramide-induced death inhibitor, can prevent sperm aging by enhancing DNA double-strand breaks (DSB) repair. We observed a significant increase in DNA damage with age and this increase was associated with a decline in the expression of key DNA DSB repair genes in mouse sperm. The haploinsufficiency of BRCA1 male mice sperm showed significantly increased DNA damage and apoptosis, along with decreased chromatin integrity when compared to similar age wild type (WT) mice. Furthermore, haploinsufficiency of BRCA1 male mice had lower sperm count and smaller litter size when crossed with WT females. The resulting embryos had a higher probability of growth arrest and reduced implantation. S1P treatment decreased genotoxic-stress-induced DNA damage in sperm and enhanced the expressions of key DNA repair genes such as BRCA1. Co-treatment with an ATM inhibitor reversed the effects of S1P, implying that the impact of S1P on DNA repair is via the ATM-mediated pathway. Our findings indicate a key role for DNA damage repair mechanism in the maintenance of sperm integrity and suggest that S1P can improve DNA repair in sperm. Further translational studies are warranted to determine the clinical significance of these findings and whether S1P can delay male reproductive aging. There is mounting evidence that sperm quality declines with age, similar to that of the oocyte. However, the reasons behind this decline are poorly understood and there is no medical intervention to improve sperm quality. Our study suggests a strong role for DNA damage repair in maintenance of sperm quality, and for the first time, a potential pharmaceutical approach to prevent sperm aging.
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