Endocrine Abstracts

Introduction: Epigenetics is defined as heritable changes in gene expression without changes in the DNA sequence. The transgenerational epigenetic inheritance of diseases is an emerging area of research. Multiple environmental factors including toxicants are associated with the transgenerational inheritance of increased disease susceptibility. 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. The present review explores the literature on transgenerational inheritance of obesity caused by EDCs.

Methods: A systematic search of literature was conducted using the search terms epigenetics, EDCs, obesogens, pregnancy, embryonic/fetal development, transgenerational inheritance, and obesity.

Results: By inducing epigenetic changes in germ cells (egg or sperm), the environment directly influences genetic variation, inheritance, phenotypic variation, and adaptation. The changes propagate through multiple generations without any new exposure to the initiating factor. The obesity pandemic 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, tributyltin, and phthalates) during critical windows of embryonic/fetal development (e.g., Weeks 4–8) can induce transgenerational inheritance of increased obesity risk. Even if the exposure is removed, the transgenerational phenotype can persist through multiple generations. The proposed mechanisms implicated in transgenerational inheritance caused by EDCs include DNA methylation (the most studied mechanism), histone methylation, histone retention, chromatin structure alteration, and non-coding RNAs expression. With a direct exposure of the parents (considered the F0 generation) and the fetus (considered the F1 generation), the true transgenerational transmission is the F3 generation and beyond for the exposure of a pregnant female and the F2 generation and beyond for the exposure of a non-pregnant female or a male. Most reported human studies on transgenerational epigenetic inheritance are up to the F2 generation.

Conclusion: Exposure to a subset of EDCs called obesogens causes the metabolic programming of obesity and its transgenerational inheritance. Bisphenol A is one of the most widespread obesogens affecting humans. A better understanding of the mechanisms of the transgenerational inheritance is critical for the implementation of preventive strategies in the fight against obesity. Every effort should be made to minimize or avoid the exposure to obesogens, especially during the windows of sensitivity of the embryo/fetus.