Transgenerational Inheritance of Obesity Caused by Endocrine-Disrupting Chemicals

The transgenerational epigenetic inheritance of diseases is an emerging area of research. Multiple environmental factors including toxicants are involved. Endocrine-disrupting chemicals (EDCs) are a heterogeneous group of exogenous chemicals or chemical mixtures that interfere with the action of hormones. The obesity pandemic cannot be explained solely by alterations in food intake and/or decrease in exercise. It coincides with the exponential increase in the number of EDCs present in the air, water, and food. Some EDCs called obesogens can promote weight gain despite normal diet and exercise. At least 50 obesogens have been identified. Exposure to obesogens (e.g., bisphenol A, phthalates, and tributyltin) during critical windows of embryonic/fetal development (e.g., Weeks 4-8) can induce transgenerational inheritance of increased obesity risk. By inducing epigenetic changes in germ cells (egg or sperm), the EDCs directly influence genetic variation, inheritance, phenotypic variation, and adaptation. The changes propagate and the transgenerational phenotype can persist through multiple generations without any new exposure to the initiating factor. The proposed mechanisms implicated in transgenerational inheritance caused by EDCs include deoxyribonucleic acid (DNA) methylation (the most studied mechanism), histone methylation, histone retention, chromatin structure alteration, and non-coding ribonucleic acids (RNAs) expression. A better understanding of the mechanisms of the transgenerational inheritance is critical for the implementation of preventive strategies in the fight against obesity pandemic. Every effort should be made to minimize or avoid the exposure to obesogens, especially during the windows of sensitivity of the embryo/fetus.