O-111 Developing therapeutic strategies targeting ovarian fibrosis to extend female reproductive longevity

Abstract

The female reproductive system ages in otherwise relatively young individuals; fertility begins to decline in women in their mid-thirties and reproductive function ceases at menopause around age fifty. Ovarian aging is characterized by a loss of egg quantity and quality which translates into decreased fertility and endocrine function. Ovarian aging has broad societal ramifications as more women delay childbearing and experience infertility. Moreover, due to health advances, women are living well post-menopause in an altered hormone milieu which can negatively impact sexual, cardiovascular, immune, bone, and cardiac health. Thus, there is a critical need to translate fundamental mechanisms of ovarian aging into therapeutic interventions that can extend ovarian function to align with modern lifestyles and improve reproductive decision-making, quality of life, and overall healthspan for women. We discovered that the aging ovary becomes inflammatory with age and this is accompanied by fibrosis caused by excess accumulation of certain extracellular matrix (ECM) proteins which causes increased ovarian stiffness. The fibrotic ovary negatively affects follicle development, egg quality, and ovulation, and it provides a suitable niche for ovarian cancer. In this presentation, we will discuss how we are moving these findings from bench-to-bedside to develop tissue stiffness as a biomarker of ovarian aging and fibrosis as a therapeutic target to extend reproductive longevity and promote healthy aging.