Endocrine disrupting chemicals (EDCs) are defined as exogenous chemicals, or mixtures of chemicals, that can interfere with any aspect of hormone action. The field of endocrine disruption is historically rooted in wildlife biology and reproductive endocrinology where EDCs are demonstrated contributors to infertility, premature puberty, endometriosis, and other disorders. Recently, EDCs have been implicated in metabolic syndrome and obesity. Adipose tissue is a true endocrine organ and, therefore, an organ that is highly susceptible to disturbance by EDCs. A subset of EDCs, called "obesogens," promote adiposity by altering programming of fat cell development, increasing energy storage in fat tissue, and interfering with neuroendocrine control of appetite and satiety. Obesity adds more than $200 billion to US healthcare costs and the number of obese individuals continues to increase. Hence, there is an urgent, unmet need to understand the mechanisms underlying how exposures to certain EDCs may predispose our population to be obese. In this review, we discuss the history of obesogen discovery from its origins in reproductive biology to its latest role in the transgenerational inheritance of obesity in mice. We discuss the development of adipose tissue in an embryo, maintenance of adipocyte number in adults, how EDC disruption programs stem cells to preferentially make more adipocytes, the mechanisms by which chemicals can permanently alter the germline epigenome, and whether there are barriers to EDCs in the gametes.

Obesity and metabolic syndrome diseases have exploded into an epidemic of global proportions. The generally accepted cause of obesity is overconsumption of calorie-dense food and diminished physical activity (the calories in-calories out model). However, emerging evidence demonstrates that environmental factors can predispose exposed individuals to gain weight, irrespective of diet and exercise. The environmental obesogen model proposes that chemical exposure during critical stages in development can influence subsequent adipogenesis, lipid balance and obesity. Obesogens are chemicals that inappropriately stimulate adipogenesis and fat storage. Numerous obesogens have been identified in recent years and some of these have been shown to act through the peroxisome proliferator activated receptor gamma, the master regulator of adipogenesis. Others act through as yet unidentified pathways. Notably, some of these obesogens elicit transgenerational effects on a variety of health endpoints, including obesity in offspring after exposure of pregnant F0 females. Thus, prenatal exposure to xenobiotic compounds can have lasting, potentially permanent effects on the offspring of exposed animals. Transgenerational effects of chemical exposure raise the stakes in the debate about whether and how endocrine disrupting chemicals should be regulated.