Macarena B. Gonzalez Ph.D. , Nicole O. McPherson Ph.D. , Haley S. Connaughton B.Sc. , Yasmyn E. Winstanley Ph.D. , David T. Kennedy Ph.D. , Carl A. Campugan Ph.D. , Mark A. Febbraio Ph.D. , Michael Barry M.C.E. , Ryan D. Rose Ph.D. , Rebecca L. Robker Ph.D.
{"title":"线粒体激活剂bp -15保护精子质量免受氧化损伤，提高胚胎发育能力。","authors":"Macarena B. Gonzalez Ph.D. , Nicole O. McPherson Ph.D. , Haley S. Connaughton B.Sc. , Yasmyn E. Winstanley Ph.D. , David T. Kennedy Ph.D. , Carl A. Campugan Ph.D. , Mark A. Febbraio Ph.D. , Michael Barry M.C.E. , Ryan D. Rose Ph.D. , Rebecca L. Robker Ph.D.","doi":"10.1016/j.xfss.2024.12.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>To study the efficacy of mitochondrial activator BGP-15 to preserve sperm quality and competence against cellular damage.</div></div><div><h3>Design</h3><div>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.</div></div><div><h3>Subjects</h3><div>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.</div></div><div><h3>Exposure</h3><div>Mouse spermatozoa were treated with 10-μM BGP-15. Human spermatozoa were treated with BGP-15 at doses from 1 to 100 μM.</div></div><div><h3>Main Outcome Measures</h3><div>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.</div></div><div><h3>Results</h3><div>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%.</div></div><div><h3>Conclusion</h3><div>BGP-15 protects sperm against cellular damage and has the potential to improve ART outcomes.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"6 1","pages":"Pages 42-54"},"PeriodicalIF":1.9000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mitochondrial activator BGP-15 protects sperm quality against oxidative damage and improves embryo developmental competence\",\"authors\":\"Macarena B. Gonzalez Ph.D. , Nicole O. McPherson Ph.D. , Haley S. Connaughton B.Sc. , Yasmyn E. Winstanley Ph.D. , David T. Kennedy Ph.D. , Carl A. Campugan Ph.D. , Mark A. Febbraio Ph.D. , Michael Barry M.C.E. , Ryan D. Rose Ph.D. , Rebecca L. Robker Ph.D.\",\"doi\":\"10.1016/j.xfss.2024.12.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>To study the efficacy of mitochondrial activator BGP-15 to preserve sperm quality and competence against cellular damage.</div></div><div><h3>Design</h3><div>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.</div></div><div><h3>Subjects</h3><div>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.</div></div><div><h3>Exposure</h3><div>Mouse spermatozoa were treated with 10-μM BGP-15. Human spermatozoa were treated with BGP-15 at doses from 1 to 100 μM.</div></div><div><h3>Main Outcome Measures</h3><div>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.</div></div><div><h3>Results</h3><div>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%.</div></div><div><h3>Conclusion</h3><div>BGP-15 protects sperm against cellular damage and has the potential to improve ART outcomes.</div></div>\",\"PeriodicalId\":73012,\"journal\":{\"name\":\"F&S science\",\"volume\":\"6 1\",\"pages\":\"Pages 42-54\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"F&S science\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666335X24000818\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"F&S science","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666335X24000818","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/14 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Mitochondrial activator BGP-15 protects sperm quality against oxidative damage and improves embryo developmental competence
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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