Methionine increases yolk production to offset the negative effect of caloric restriction on reproduction without affecting longevity in C. elegans

Abstract

Caloric restriction (CR) or Dietary restriction (DR) is known to improve health and in many cases increases lifespan. However, its negative effect on reproduction has not been fully studied. Practicing CR/DR without adequate knowledge on its side effect may risk complications such as infertility, birth defect, or malnutrition. In this study, by using several CR strategies in C. elegans, we examine key functions of reproduction including embryonic development and larvae growth. We find that CR significantly decreases the survival of embryos and slows the growth of the offspring. We further determine that defect in oocyte but not sperm is responsible for the compromised reproduction under CR. Interestingly, adding methionine to the medium reverses the reproduction defects, but does not affect the long lifespan resulted from CR. The beneficial effect of methionine on reproduction requires the yolk protein vitellogenin. CR down-regulates vitellogenin expression, which can be reversed by supplementing methionine in the food. Lacking the yolk protein transport due to rme-2 mutation blocks methionine's beneficial effects. Our study has revealed a novel, methionine-mediated genetic pathway linking nutrient sensing to reproduction and suggested methionine as a potential food supplement to mitigate the side effect of CR.

Maternal Caffeine Intake Disrupts Eggshell Integrity and Retards Larval Development by Reducing Yolk Production in a Caenorhabditis elegans Model

“…However, we propose that vitellogenin can partially contribute to the survival of embryos and other factors can compensate for the requirement of vitellogenin during embryogenesis. This is supported by the findings that 23% of live embryos were retained even with complete loss of vitellogenin in oocytes in rme-2 mutants [35]; and that vitellogenin production was remarkably decreased under dietary restriction in C. elegans, causing increased embryonic lethality that was suppressed by methionine supplement [39]. In addition, larval growth retardation in the F1 generation of caffeine-ingested mothers in the present study reveals that vitellogenin is indeed an intergenerational protein.…”

Methionine Supplementation Alleviates the Germ Cell Apoptosis Increased by Maternal Caffeine Intake in a C. elegans Model

“…We previously found a reduction in vitellogenesis in CIAs [ 24 ]. Vitellogenesis in C. elegans at the adult stage is regulated by methionine supplementation [ 35 ]. Considering these findings, we propose that the reduction in vitellogenesis in CIAs is due to alterations in the methionine cycle.…”

Vitamin B12 Supplementation Improves Oocyte Development by Modulating Mitochondria and Yolk Protein in a Caffeine-Ingested Caenorhabditis elegans Model

“…We have previously shown that caffeine intake significantly reduces vitellogenesis [9]. Recently, methionine has been suggested to play a key function during vitellogenesis in dietary restriction [20]. Therefore, we investigated whether methionine metabolism and vitellogenesis were regulated by caffeine intake in C. elegans.…”

“…In addition, methionine improves egg production in chickens [18] and milk production in dairy cows [19], suggesting that it plays an important role in nutrient metabolism in animal reproduction. Interestingly, methionine supplementation increases vitellogenesis to mitigate the negative effects of calorie restriction in C. elegans [20]. In methionine metabolism, vitamin B12 (cobalamin) serves as a methyl group carrier in the methyltetrahydrofolate-homocysteine methyltransferase enzyme, also known as methionine synthase, and as a cofactor for mitochondrial methylmalonyl-CoA mutase (Figure 1A) [21,22].…”