Chapter 9 - Female Reproductive Aging: From Consequences to Mechanisms, Markers, and Treatments

Abstract

Aging is universal and underlies chronic disease as well as tissue and cellular deterioration. The female reproductive system is the first to age in humans, with functional decline occurring decades prior to other organs. Reproductive aging is associated with a decrease in both the number and quality of eggs within the ovary, which together contribute to increased incidences of miscarriages, infertility, and birth defects. Reproductive aging also affects general health because ovarian hormones, such as estrogen, regulate downstream organ systems. The negative consequences of female reproductive aging are becoming more prevalent as women globally are delaying childbearing and more women are living well beyond menopause due to life-extending medical interventions and advances. Here we synthesize data from mouse models and humans to define age-associated changes in endocrinology, gamete quality, and the somatic ovarian environment, and we describe how genetic, lifestyle, and environmental factors accelerate such changes. There is a clinical need to generate tools to assess reproductive aging and to develop methods to improve reproductive outcomes in the setting of advanced reproductive age. The delineation of new biological mechanisms underlying reproductive aging is continuously informing therapeutic interventions, which are largely focused on targeting mitochondrial function. However, the diversity of therapeutic strategies is likely to expand as we learn more about the complex, multifactorial phenomenon of reproductive aging, which will impact every single female.