Elsevier

Reproductive Toxicology

Volume 23, Issue 3, April–May 2007, Pages 290-296
Reproductive Toxicology

Review
Developmental exposure to endocrine disruptors and the obesity epidemic

https://doi.org/10.1016/j.reprotox.2006.12.010Get rights and content

Abstract

Xenobiotic and dietary compounds with hormone-like activity can disrupt endocrine signaling pathways that play important roles during perinatal differentiation and result in alterations that are not apparent until later in life. Evidence implicates developmental exposure to environmental hormone-mimics with a growing list of health problems. Obesity is currently receiving needed attention since it has potential to overwhelm health systems worldwide with associated illnesses such as diabetes and cardiovascular disease. Here, we review the literature that proposes an association of exposure to environmental endocrine disrupting chemicals with the development of obesity. We describe an animal model of developmental exposure to diethylstilbestrol (DES), a potent perinatal endocrine disruptor with estrogenic activity, to study mechanisms involved in programming an organism for obesity. This experimental animal model provides an example of the growing scientific field termed “the developmental origins of adult disease” and suggests new targets of abnormal programming by endocrine disrupting chemicals.

Introduction

Over the last decade, mounting evidence from wildlife, epidemiological, laboratory animal, and in vitro studies has shown that numerous environmental and dietary chemicals can interfere with an organism's complex endocrine signaling mechanisms and result in adverse consequences [1], [2], [3], [4], [5], [6], [7]. Initial concern focused on exposure to chemicals with estrogenic activity and their contributions to reproductive tract disease and dysfunction; however, it has become increasingly evident that estrogenicity is not the only important endocrine mode of action, and that the reproductive tract is not the only organ system affected. Interest has broadened to include chemicals that mimic or interfere with the normal actions of all endocrine hormones including estrogens, androgens, progestins, thyroid, hypothalamic and pituitary hormones; these chemicals are now collectively referred to as “endocrine disruptors”. Organ systems known to be involved include reproductive tract tissues, but have been expanded to include other tissues such as those of the respiratory, cardiovascular, and neuroendocrine systems. Most recently, conference proceedings and reports have focused on the involvement of environmental chemicals in the growing obesity problem [8], [9], [10]. A newly published study points out the effects of environmental chemicals and their disruption of normal development and homeostatic controls over adipogenesis and energy balance [11]. While the full extent of the health consequences of endocrine disrupting chemicals is unknown, we are only beginning to understand how chemicals act as endocrine disruptors, and to fully appreciate the complexities and interactions of endocrine signaling mechanisms.

Section snippets

The developmental basis of adult disease

Adult exposure to endocrine disrupting chemicals is certainly an important factor, however focus on the fetus and/or neonate is of primary concern since developing organisms are extremely sensitive to perturbation by chemicals with hormone-like activity. Adverse effects may be most pronounced in the developing organism and occur at concentrations of the chemical that are far below levels that would be considered harmful in the adult. The exquisite sensitivity of the developing fetus and neonate

The obesity epidemic

Obesity, defined as excessive body fat (>25% men; >30% women), is fast becoming a significant human health crisis that is receiving worldwide attention [18]. The prevalence of obesity has risen dramatically in wealthy developed countries over the last two to three decades but it is also on the rise in poor nations. The World Health Organization (WHO) has declared excessive weight as one of the top 10 health risks in the world, and has estimated that the number of overweight people in the world

The developmental exposed DES animal model to study obesity

For over 30 years, research in our laboratory has focused on the effects of estrogenic compounds on development and differentiation. Our working premise has been that the developing organism is extremely sensitive to perturbation by chemicals with estrogenic or endocrine disrupting activity, and that exposure to these chemicals during critical stages of differentiation may have permanent long lasting consequences, some of which may not be expressed or detected until later in life.

Summary and conclusions

Taken together, our data supports the idea that brief exposure early in life to environmental endocrine disrupting chemicals, especially those with estrogenic activity like DES, increases body weight as the mice age. Our data also suggest that these chemicals may contribute to overweight and obesity and other obesity-associated diseases such as type 2 diabetes and cardiovascular disease. Whether our results can be extrapolated to humans as well as the reproductive abnormalities from the DES

Acknowledgments

The authors would like to thank Page Myers for expert technical assistance in obtaining glucose measurements for this study. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.

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