ReviewDevelopmental exposure to endocrine disruptors and the obesity epidemic
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.
References (32)
- et al.
The impact of obesity on psychological well-being
Best Pract Res Clin Endocrinol Metab
(2005) - et al.
Effects of maternal xenoestrogen exposure on development of the reproductive tract and mammary gland in female CD-1 mouse offspring
Reprod Toxicol
(2004) The association of body fat distribution with hypertension, hypertensive heart disease, coronary heart disease, diabetes and cardiovascular risk factors in men and women aged 18–79 years
J Chronic Dis
(1987)- et al.
Chemically-induced alterations in sexual and functional development: the wildlife/human connection
(1992) - et al.
Developmental effects of endocrine-disrupting chemicals in wildlife and humans [see comments]
Environ Health Perspect
(1993) - et al.
Our stolen future
(1996) Estrogens in the environment
(1985)Estrogens in the environment II
(1995)Diethylstilbestrol (DES) and environmental estrogens influence the developing female reproductive system
(1999)- 2005 Update endocrine disruptors: effects on male and female reproductive systems. Boca Raton: CRC...
Developmental exposure to estrogenic compounds and obesity
Birth Defects Res A Clin Mol Teratol
Developmental origins and environmental influences—introduction. NIEHS symposium
Birth Defects Res A Clin Mol Teratol
Endocrine disruptors and the obesity epidemic
Toxicol Sci
Environmental obesogens: organotins and endocrine disruption via nuclear receptor signalling
Endocrinology
The fragile fetus
Fetal origins of adult disease: strength of effects and biological basis
Int J Epidemiol
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