Project Grant R01HD120348

This project grant, awarded by the National Institute of Child Health and Human Development (NICHD) under the Child Health and Human Development Extramural Research program (CFDA 93.865), supports basic and translational research investigating the relationship between ovarian mechanical properties and follicle development. Washington University in St. Louis will conduct a comprehensive four-year study (July 1, 2026 through March 31, 2031) with $461,435 in federal funding to elucidate how age-associated increases in ovarian tissue stiffness contribute to reproductive aging and impaired fertility. The research will establish molecular mechanisms linking mechanical microenvironment changes to follicle inflammation and declining oocyte quality through three integrated research aims examining microenvironment stiffness effects on inflammation, mechanical signal integration in follicle function, and in vivo impacts on oocyte quality and fertility outcomes.

The project addresses a significant gap in understanding reproductive aging by testing the hypothesis that follicles detect and respond to increased ovarian stiffness through inflammatory pathways that create a positive feedback loop impairing reproductive health. Deliverables include comprehensive mechanistic data on stiffness-derived changes in ovarian function with potential long-term applications in developing novel therapeutic strategies targeting mechanotransduction pathways to reverse or delay ovarian aging. This fundamental research directly supports NICHD's mission to advance understanding of human development and reproductive health across the lifespan.