Mitochondrial activator BGP-15 protects sperm quality against oxidative damage and improves embryo developmental competence
Date
2025
Authors
Gonzalez, M.B.
McPherson, N.O.
Connaughton, H.S.
Winstanley, Y.E.
Kennedy, D.T.
Campugan, C.A.
Febbraio, M.A.
Barry M C E, M.
Rose, R.D.
Robker, R.L.
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Journal article
Citation
F&S Science, 2025; 6(1):42-54
Statement of Responsibility
Macarena B. Gonzalez, Nicole O. McPherson, Haley S. Connaughton, Yasmyn E. Winstanley, David T. Kennedy, Carl A. Campugan, Mark A. Febbraio, Michael Barry, Ryan D. Rose, Rebecca L. Robker
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Abstract
Objective: To study the efficacy of mitochondrial activator BGP-15 to preserve sperm quality and competence against cellular damage. Design: Spermatozoa from mice or humans were treated in vitro with BGP-15, and sperm quality markers were assessed. Spermatozoa from young (8–12 weeks old) or reproductively old (>14 months old) mice were treated with BGP-15 for 1 hour and assessed for sperm quality and preimplantation embryo development after in vitro fertilization. The safety of BGP-15 on offspring outcomes was assessed through embryo transfers. In parallel studies, spermatozoa from healthy (not infertile) men were incubated in hydrogen peroxide, to induce oxidative stress, plus increasing doses of BGP-15, and sperm quality was evaluated. Spermatozoa from patients undergoing assisted reproductive technology (ART) treatment were incubated in the optimized dose of BGP-15 for 30 minutes, and sperm quality was assessed. Subjects: C57BL/6 mice (N = 4–15 per group) for sperm quality and embryo development. CBAF1 mice (n = 6 per group) produced embryos for transfer. Human spermatozoa were from men with no infertility diagnosis (n = 14-20) or men undergoing ART (n = 33) at a local fertility clinic. Exposure: Mouse spermatozoa were treated with 10-μM BGP-15. Human spermatozoa were treated with BGP-15 at doses from 1 to 100 μM. Main Outcome Measures Sperm quality measures (mouse and human) included motility, mitochondrial membrane potential (JC-1 dye), deoxyribonucleic acid (DNA) fragmentation (“HALO” assay), and DNA oxidation (8-oxoguanine immunodetection). Mouse embryo and offspring measures included on-time development after in vitro fertilization, morphokinetic analysis, and blastocyst inner cell mass and trophectoderm cell number, and growth and development from birth to 21 days postnatally. Results: BGP-15 increased sperm motility and mitochondrial membrane potential and decreased DNA oxidation in old mice. BGP-15 improved on-time development of 2-cell and blastocyst embryos and increased the inner cell mass blastomere number. Embryos from BGP-15-treated mouse spermatozoa produced normal offspring. In human spermatozoa subjected to in vitro oxidative stress, BGP-15 increased motility by 45% and prevented DNA fragmentation (by 45%) and oxidative damage (by 60%). In spermatozoa from men attending a fertility clinic, BGP-15 increased motility by 12% and reduced both DNA oxidation and fragmentation by >20%. Conclusion: BGP-15 protects sperm against cellular damage and has the potential to improve ART outcomes.
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© 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.