Maternal dietary imbalances and toxicant exposures increase offspring obesity risk through persistent epigenetic changes.
Deficiencies in one-carbon donors or excess caloric intake can lead to lasting changes in genes that regulate fat storage and energy balance.
Prenatal exposure to harmful substances like endocrine disruptors and heavy metals can worsen obesity risk by modifying DNA and associated regulatory mechanisms.
A combination of poor nutrition and toxic exposures, especially in low- and middle-income countries, may create a 'dual burden' that heightens epigenetic changes.
Certain nutrients, such as methyl donors and antioxidants, might help counteract harmful epigenetic alterations caused by toxic exposures.
Simplified
BACKGROUND: The developmental origins of health and disease () 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.
Key numbers
3.80 billion adults
Projected obesity prevalence
Estimated number of adults projected to be overweight or obese by 2050.
60 million
60 million individuals
Estimated number of people in Pakistan exposed to arsenic in drinking water.
25%
25%
Proportion of food crops estimated to be contaminated with mycotoxins globally.
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