Gonzalez Macarena B, McPherson Nicole O, Connaughton Haley S, Winstanley Yasmyn E, Kennedy David T, Campugan Carl A, Febbraio Mark A, Barry Michael, Rose Ryan D, Robker Rebecca L
School of Biomedicine, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
School of Biomedicine, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia; Genea Fertility SA, Adelaide, South Australia, Australia; Freemasons Centre for Male Health and Wellbeing, University of Adelaide, Adelaide, South Australia, Australia.
F S Sci. 2025 Feb;6(1):42-54. doi: 10.1016/j.xfss.2024.12.001. Epub 2024 Dec 14.
To study the efficacy of mitochondrial activator BGP-15 to preserve sperm quality and competence against cellular damage.
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.
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.
Mouse spermatozoa were treated with 10-μM BGP-15. Human spermatozoa were treated with BGP-15 at doses from 1 to 100 μM.
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.
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%.
BGP-15 protects sperm against cellular damage and has the potential to improve ART outcomes.
研究线粒体激活剂BGP - 15在保护精子质量及抵抗细胞损伤能力方面的功效。
将来自小鼠或人类的精子在体外用BGP - 15处理，然后评估精子质量指标。对年轻（8 - 12周龄）或生殖衰老（>14月龄）小鼠的精子用BGP - 15处理1小时，体外受精后评估精子质量和植入前胚胎发育情况。通过胚胎移植评估BGP - 15对后代结局的安全性。在平行研究中，将健康（非不育）男性的精子在过氧化氢中孵育以诱导氧化应激，再加入递增剂量的BGP - 15，然后评估精子质量。对接受辅助生殖技术（ART）治疗的患者的精子用优化剂量的BGP - 15孵育30分钟，评估精子质量。
用于精子质量和胚胎发育研究的C57BL/6小鼠（每组4 - 15只）。用于胚胎移植的CBAF1小鼠（每组6只）。人类精子来自当地生育诊所未诊断为不育的男性（14 - 20例）或接受ART治疗的男性（33例）。
小鼠精子用10 μM的BGP - 15处理。人类精子用1至100 μM剂量的BGP - 15处理。
精子质量指标（小鼠和人类）包括活力、线粒体膜电位（JC-1染料法）、脱氧核糖核酸（DNA）片段化（“HALO”检测法）和DNA氧化（8-氧代鸟嘌呤免疫检测法）。小鼠胚胎和后代指标包括体外受精后的按时发育、形态动力学分析、囊胚内细胞团和滋养外胚层细胞数量，以及出生至出生后21天的生长发育情况。
BGP - 15可提高老年小鼠精子的活力和线粒体膜电位，并降低DNA氧化。BGP - 15改善了2细胞和囊胚胚胎的按时发育，并增加了内细胞团卵裂球数量。用BGP - 15处理的小鼠精子产生的胚胎发育出正常后代。在经受体外氧化应激的人类精子中，BGP - 15使活力提高了45%，并防止了DNA片段化（降低45%）和氧化损伤（降低60%）。在生育诊所男性的精子中，BGP - 15使活力提高了12%，并使DNA氧化和片段化均降低了>20%。
BGP - 15可保护精子免受细胞损伤，并有可能改善ART结局。
