Transgenerational Developmental Programming of Ovarian Reserve

Exposure to an adverse early-life environment leads to long-term health problems, many of which are recapitulated in subsequent generations. The female reproductive tract is particularly sensitive to early-life influences, and plays a pivotal role in programming the conceptus. We examine the influence of suboptimal grandmaternal diet on reproductive potential of granddaughters in the absence of any further dietary manipulations in the daughters in a rat low-protein diet model. Exposure to low-protein grand-maternal diet leads to decreased ovarian reserve and increased intra-abdominal fat mass in granddaughters, accompanied by accelerated accumulation of oxidative stress and mtDNA copy number instability in the ovaries. Ovarian telomere length declines more rapidly in the exposed granddaughters, indicating accelerated ageing in the reproductive tract. Thus, we demonstrate that suboptimal grandmaternal diet during pregnancy accelerates reproductive ageing across subsequent generations. These findings have important implications for understanding both individual rates of decline in fertility with age, and the clinical impact of current global trends towards delayed childbearing.