Maternal Nutrition, Toxicants, and Epigenetic Programming of Obesity Across Generations

Abstract

Background: The developmental origins of health and disease (DOHaD) framework highlights the importance of the intrauterine environment in shaping lifelong health outcomes. Maternal nutrition, toxic exposures, and epigenetic reprogramming are key factors influencing offspring susceptibility to obesity and cardiometabolic disorders. However, prior reviews have typically addressed nutrition and toxicants separately, limiting insights into their combined effects on the fetal epigenome. This review integrates current evidence on how maternal nutrition and toxicant exposures converge through epigenetic mechanisms to influence obesity risk, while outlining translational opportunities for mitigating intergenerational metabolic disease. Methods: A narrative review was conducted of studies published from 2000 to 2025, sourced from PubMed, Scopus, and Web of Science, supplemented by manual screening. Search terms included maternal nutrition, environmental toxicants, epigenetic mechanisms, and offspring obesity outcomes. Studies on animal models, human cohorts, and intervention trials were included, focusing on links between maternal exposures, epigenetic changes, and metabolic disease. Results: Maternal dietary imbalances, such as deficiencies in one-carbon donors or excess caloric intake, cause persistent epigenetic changes on genes regulating adipogenesis and energy homeostasis, increasing offspring obesity risk. Prenatal exposure to environmental toxicants, including endocrine disruptors and heavy metals, amplifies these vulnerabilities by altering DNA methylation, histone modifications, and noncoding RNA networks. Combined nutritional deficits and toxicant exposures, particularly in low- and middle-income countries (LMICs), create a “dual burden” that intensifies epigenetic instability. Nutrients like methyl donors and antioxidants may mitigate toxicant-induced epimutations, offering potential for precision maternal nutrition interventions. Conclusion: Maternal nutrition and toxicant exposures interact through epigenetic mechanisms to program obesity and related diseases. Addressing these factors through precision nutrition, stricter environmental regulations, and early-life epigenetic biomarkers offers promising prevention strategies. Large, diverse, multi-generational cohorts and multi-omics approaches are needed to strengthen causal inference and inform equitable policies to break the intergenerational cycle of metabolic disease. Plain Language Summary: This study explores how a mother’s diet and exposure to environmental pollutants during pregnancy can shape her child’s future risk of obesity and related diseases such as diabetes and heart disease. It explains that what happens in the womb can “program” a baby’s metabolism for life through changes in gene activity known as epigenetic modifications which are chemical tags that switch genes on or off without changing DNA. Poor maternal nutrition, whether from eating too much fat and sugar or lacking key vitamins like folate and B 12 can alter these epigenetic marks, increasing the child’s tendency to gain weight. At the same time, exposure to environmental toxicants like plastics (which contains BPA), heavy metals, or pesticides can make these effects worse. When both poor nutrition and toxic exposure occur together, especially in low-income settings, the risk becomes even greater. The review also highlights that healthy diets rich in folate, antioxidants, and omega-3 fats may help protect against these harmful effects. New technologies that study genes, metabolites, and gut bacteria together (multi-omics) are helping scientists identify early biomarkers of risk. Ultimately, the study calls for integrated maternal health policies that combine good nutrition with stronger environmental protections to prevent obesity from being passed down across generations. Keywords: toxic exposures, epigenetics, histone modifications, endocrine disruptors, fetal programming, maternal precision nutrition