Grant: Project Grant

Abnormally elevated insulin is associated with many detrimental health effects. For instance, obesity is often accompanied by a rise in insulin levels, and has negative impacts on fertility and female reproductive health. Notably, interventions that reduce insulin signaling are protective against infertility in mouse models of obesity. The highly conserved signaling pathway that responds to insulin plays a crucial role in coordinating metabolism, reproduction, and lifespan in organisms ranging from worms to humans. Worms with genetic mutations that reduce signaling via this insulin signaling pathway show improvements in the quality of their egg cells, a delay in the age-related decline in reproductive capacity, and a dramatic extension of lifespan. Our proposed work builds on these previous findings to investigate the hypothesis that preventing insulin excess could slow the age-related decline in female reproductive health and egg cell quality. Using our mouse model of genetically reduced insulin under high-fat diet conditions that cause obesity and worsen reproductive health, we will determine how suppressing insulin levels affects egg cell quality and reproductive success during aging. Since high insulin levels can be normalized in humans via lifestyle changes, we anticipate that our work could inform effective strategies to manage female reproductive health by limiting excess insulin.