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

Abstract

Vitamin B12 is an essential cofactor involved in the function of two enzymes: cytosolic methionine synthase and mitochondrial methylmalonic-CoA mutase. In our previous studies, caffeine (1,3,7-trimethylxanthine), the most popular bioactivator, was shown to reduce yolk protein (vitellogenin) and fertility in a Caenorhabditis elegans model. Based on the previous finding that methionine supplementation increases vitellogenesis in C. elegans, we investigated the role of vitamin B12 in methionine-mediated vitellogenesis during oogenesis in caffeine-ingested animals (CIA). Vitamin B12 supplementation improved vitellogenesis and reduced oxidative stress by decreasing mitochondrial function in CIA. Furthermore, the decreased number of developing oocytes and high levels of reactive oxygen species in oocytes from CIA were recovered with vitamin B12 supplementation through a reduction in mitochondrial stress, which increased vitellogenesis. Taken together, vitamin B12 supplementation can reverse the negative effects of caffeine intake by enhancing methionine-mediated vitellogenesis and oocyte development by reducing mitochondrial stress.

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

“…We previously showed that the decrease in reproduction and vitellogenesis caused by caffeine intake was improved by vitamin B12 supplementation, which acts as a co-factor in the Met/SAM cycle in C. elegans [ 34 ]. Considering the important role of methionine in cellular metabolism, we investigated its role in reproduction in caffeine-ingested animals (CIAs).…”

“…We found that caffeine intake significantly reduced methionine levels and vitellogenesis and, thus, increased germ cell apoptosis. Recently, it has been reported that maternal caffeine intake causes mitochondrial stress in the germ line of C. elegans [ 34 ], but the mechanism by which caffeine intake induced mitochondrial stress in the germline remains unclear. Interestingly, some studies have demonstrated an interrelationship between methionine metabolism and mitochondrial function with direct relevance [ 36 , 37 , 38 ].…”