Intergenerational effects of dietary restriction on insulin/IGF signaling and reproductive development

Abstract

The roundworm C. elegans transiently arrests larval development to survive extended starvation (1), but such early-life starvation reduces reproductive success (2, 3). Maternal dietary restriction (DR) buffers progeny from starvation, increasing reproductive success (4). It is unknown why early-life starvation decreases reproductive success and how maternal diet modifies this process. We show here that extended starvation in first-stage (L1) larvae followed by unrestricted feeding results in a variety of abnormalities in the reproductive system, including glp-1/Notch-sensitive germ-cell tumors and uterine masses that express neuronal and epidermal markers. We found that maternal DR reduces the penetrance of starvation-induced abnormalities, including tumors. Furthermore, we show that maternal DR reduces insulin/IGF signaling (IIS) in progeny, and that daf-16/FoxO and skn-1/Nrf, transcriptional effectors of IIS, are required in progeny for maternal DR to suppress abnormalities. daf-16/FoxO activity in somatic tissues is sufficient to suppress starvation-induced abnormalities, suggesting cell-nonautonomous regulation of reproductive system development. This work reveals complex inter- and intra-generational effects of nutrient availability mediated by IIS with consequences on developmental integrity and reproductive success.\n\nOne Sentence SummaryIntergenerational effects of diet on IIS