Experimental studies to analyze prenatal programming of obesity later in life by environmental endocrine disruptors

Introduction: Endocrine disrupting compounds (EDCs) present in food and drinks are a potential factor implicated in the worldwide pandemic of obesity. Following the Developmental Origins of Health and Disease (DOHaD) principle, exposure to EDCs during the sensitive perinatal period can program the fetus/neonate towards increased susceptibility to develop obesity later in life. This altered programming may occur via DNA methylation, an epigenetic mechanism, in target tissues involved in energy homeostasis and appetite regulation, or via altered cell differentiation. In the EU-FP7 project OBELIX, in vivo and in vitro experimental studies are designed to provide observational and mechanistic evidence to support epidemiological associations between exposure to major EDCs and development of obesity later in life. Methods: In in vivo studies in mice, dams are exposed via the diet to emerging EDCs during the perinatal period. Offspring are then assessed for obesity related parameters. Materials, e.g. DNA from fat tissue, will be examined for epigenetic changes, through analysis of DNA methylation by CpG island microarray analysis, HPLC and methylation sensitive PCR. Furthermore, in in vitro studies, epigenetic and differentiation mechanisms will be studied by differentiating embryonic stem cells into adipocytes. Results: In the ongoing first in vivo study, the model EDC bisphenol A (BPA), induced a sustained dose-dependent increase of body weight in male offspring, but not in female F1. Conclusion: In our model, BPA acts as a programming factor resulting in overweight in developmentally exposed male mice. The underlying mechanism needs further analysis.