Transgenerational inheritance of prenatal obesogen exposure

• Obesogens are chemicals that inappropriately stimulate adipogenesis and fat storage.
• PPARγ activators such as TBT modulate critical steps of adipogenesis in vitro and in vivo.
• EDC-initiated phenotypes may be transmitted over generations via epigenetic alterations.
• Prenatal exposure to obesogens predisposes MSCs to become adipocytes by epigenetic imprinting.
• Effects of prenatal TBT exposure persist through at least the F3 generation.
• Changes in DNA methylation is a key mechanism for transgenerational effects of EDCs.

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.