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

Jordan, J. M.; Hibshman, J. D.; Kaplan, R. E. W.; Webster, A. K.; Leinroth, A.; Guzman, R.; Maxwell, C. S.; Bowman, E. A.; Hubbard, E. J. A.; Baugh, L. R.

doi:10.1101/342956

bioRxiv · 10.1101/342956

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

Jordan, J. M.·Hibshman, J. D.·Kaplan, R. E. W.·Webster, A. K.·Leinroth, A.·Guzman, R.·Maxwell, C. S.·Bowman, E. A.·Hubbard, E. J. A.·Baugh, L. R.

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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

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Jordan, J. M., Hibshman, J. D., Kaplan, R. E. W., Webster, A. K., Leinroth, A., Guzman, R., Maxwell, C. S., Bowman, E. A., Hubbard, E. J. A., Baugh, L. R.. 2018-06-08. Intergenerational effects of dietary restriction on insulin/IGF signaling and reproductive development. https://doi.org/10.1101/342956

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