Macarena B Gonzalez, Carl A Campugan, Haley S Connaughton, Eryk Andreas, Yasmyn E Winstanley, Elisha J Williams, Camilla L Dorian, Sarah A Robertson, Cheryl Shoubridge, Rebecca L Robker
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引用次数: 0
In Brief
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.
Abstract
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.
期刊介绍：
Reproduction is the official journal of the Society of Reproduction and Fertility (SRF). It was formed in 2001 when the Society merged its two journals, the Journal of Reproduction and Fertility and Reviews of Reproduction.
Reproduction publishes original research articles and topical reviews on the subject of reproductive and developmental biology, and reproductive medicine. The journal will consider publication of high-quality meta-analyses; these should be submitted to the research papers category. The journal considers studies in humans and all animal species, and will publish clinical studies if they advance our understanding of the underlying causes and/or mechanisms of disease.
Scientific excellence and broad interest to our readership are the most important criteria during the peer review process. The journal publishes articles that make a clear advance in the field, whether of mechanistic, descriptive or technical focus. Articles that substantiate new or controversial reports are welcomed if they are noteworthy and advance the field. Topics include, but are not limited to, reproductive immunology, reproductive toxicology, stem cells, environmental effects on reproductive potential and health (eg obesity), extracellular vesicles, fertility preservation and epigenetic effects on reproductive and developmental processes.
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