One Carbon Metabolism and Mammalian Pregnancy Outcomes

Abstract

One‐carbon metabolism is involved in varieties of physiological processes in mammals, including nucleic acid synthesis, amino acid homeostasis, epigenetic regulation, redox balance and neurodevelopment. The current evidence linking levels of one‐carbon nutrients during pregnancy to the development of oocytes, embryos, and placentas, as well as maternal and offspring health, is reviewed. The sources of mammalian one‐carbon units, the pathways active in mammalian one‐carbon metabolism, the maternal and fetal needs for one‐carbon units and their functions during pregnancy are described. The demand for one‐carbon metabolism is highest during pregnancy compared to the entire lifetime of a mammal. The primary types of one‐carbon metabolism in mammals are the folate cycle, methionine cycle and transsulfuration pathway, which varies at different pregnancy stages (e.g., methylation programming of embryo, neural development of fetus, fetal growth and placenta development). Therefore, an overall consideration of one‐carbon metabolism requirements for different pregnancy stages, is called for, specifically, the balance of all nutrients involved, not just one single nutrient in one‐carbon metabolism. Moreover, the establishment of an ideal one‐carbon metabolism requirement model is suggested according to the requirements for different pregnancy stages to support optimal pregnancy outcomes and maternal and offspring health.

Early Life Nutrition and Mental Health: The Role of DNA Methylation

“…We should then aim to have a healthy diet and healthy lifestyle for good mental health outcomes. Since the demand for one-carbon-associated micronutrient intake is high during pregnancy, the development of a one-carbon metabolism requirement model is needed for pregnant women to support optimal maternal and offspring health outcomes [ 117 ].…”

Epigenetic Modifier Supplementation Improves Mitochondrial Respiration and Growth Rates and Alters DNA Methylation of Bovine Embryonic Fibroblast Cells Cultured in Divergent Energy Supply

“…DNA methylation is affected by the presence or absence of metabolites and cofactors necessary for the proper function of the one-carbon metabolism cycle. Data in multiple species has shown that mutation to or deletion of enzymes in the one-carbon metabolism cycle alters embryonic and fetal development ( Narisawa et al, 2012 ; Cai et al, 2021 ). Furthermore, reduction in epigenetic modifiers to ewes altered the DNA methylation in their lambs at day 90 of gestation, where 88% of differentially methylated loci were hypomethylated or unmethylated ( Sinclair et al, 2007 ).…”

“…Throughout pregnancy, the whole and transitory energy requirements of macro-and micro-nutrients increase (Cai et al, 2021); however, during early gestation, the requirements of micronutrients, specific fatty acids, and amino acids and the interaction of these nutrients to meet the requirements for embryonic growth and differentiation are greater than the needs for whole-animal energy requirements (Koletzko et al, 2013;Marangoni et al, 2016;Cetin et al, 2019). Embryos undergo immense epigenetic remodeling during early development, and thus identifying specific micronutrient requirements vs. global energy requirements is needed.…”

Uterine Insulin Sensitivity Defects Induced Embryo Implantation Loss Associated with Mitochondrial Dysfunction‐Triggered Oxidative Stress

“…In addition, pregnancy involves physiological changes and metabolic adaptations week by week. Amino acid requirement sharply increases during the peri-implantation period [36][37][38]. Accordingly, amino acids accumulate in the endometrium in response to progesterone [39].…”