Robinson Research Institute, School of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia.
Reproduction. 2024 Aug 2;168(3). doi: 10.1530/REP-24-0105. Print 2024 Sep 1.
Aging in men is associated with diminished sperm quality and a higher incidence of altered fetal development and miscarriage in resultant pregnancies. This study in mice identifies a therapeutic compound that, when administered to aged males, improves sperm quality, subsequent embryo development and post-natal offspring health.
Aging in men is associated with diminished sperm quality and a higher incidence of altered fetal development and miscarriage in resultant pregnancies. We used a mouse model of advanced paternal age to characterize embryonic development in older male mice and tested whether pre-conception treatment with the mitochondrial activator BGP-15 improves reproductive outcomes in old males. Like older men, reproductively old male mice had higher levels of sperm DNA damage and delayed pre-implantation development, associated with a reduced fetal weight and placental weight. Analysis of neonatal outcomes of in vivo-conceived offspring found that pups sired by old males were smaller, had delayed locomotor development, and increased mortality. BGP-15 treatment for 5 days prior to conception reduced sperm DNA oxidation levels and improved on-time embryo development after IVF and pup survival. BGP-15 treatment for 3 weeks prior to conception improved on-time pre-implantation embryo development and fetal viability and increased fetal size in pregnancies sired by old males. These results validate that ageing negatively affects male fertility and offspring physiology and indicates that pre-conception treatment with BGP-15 has the potential to improve sperm quality as well as early embryo development and post-natal health.
男性衰老与精子质量下降以及由此产生的妊娠中胎儿发育改变和流产的发生率增加有关。本研究在小鼠中确定了一种治疗性化合物，当给予老年雄性时，可改善精子质量、随后的胚胎发育和产后后代健康。
男性衰老与精子质量下降以及由此产生的妊娠中胎儿发育改变和流产的发生率增加有关。我们使用了一种先进的雄性小鼠模型来描述老年雄性小鼠中的胚胎发育情况，并测试了在老年雄性中进行孕前治疗是否可以改善生殖结果。与老年男性一样，生殖衰老的雄性小鼠的精子 DNA 损伤水平更高，并且胚胎着床前发育延迟，伴随着胎儿体重和胎盘重量降低。对体内受孕后代的新生儿结局进行分析发现，老年雄性的后代体型较小，运动发育延迟，死亡率增加。在受孕前 5 天进行 BGP-15 治疗可降低精子 DNA 氧化水平，并改善 IVF 后胚胎的适时发育和幼崽的存活率。在受孕前 3 周进行 BGP-15 治疗可改善适时的胚胎着床前发育和胎儿活力，并增加由老年雄性的后代中的胎儿大小。这些结果验证了衰老会对男性生育能力和后代生理产生负面影响，并表明孕前治疗 BGP-15 有潜力改善精子质量以及早期胚胎发育和产后健康。
