Environmental Estrogens and Obesity: the Developmental Exposed DES Animal Model

obese-women image — In this 2009 study, it appears that the effects of DES on adipocytes may depend on the time of exposure and the dose, and that multiple mechanisms maybe altered resulting in the same obesity phenotype. Image Sandra Cohen-Rose.

2009 Study Abstract

Diethylstilbestrol DES, a potent synthetic estrogen, was widely prescribed to pregnant women from the 1940s through the 1970s with the mistaken belief that it could prevent threatened miscarriages. It was estimated that a range of 2 to 8 million pregnancies worldwide were exposed to DES. Today, it is well known that prenatal DES treatment resulted in a low but significant increase in neoplastic lesions, and a high incidence of benign lesions in both the male and female offspring exposed during fetal life. To study the mechanisms involved in DES toxicity, we developed experimental mouse models of perinatal (prenatal or neonatal) DES exposure over 30 years ago . Outbred CD-1 mice were treated with DES by subcutaneous injections on days 9–16 of gestation (the period of major organogenesis in the mouse) or days 1–5 of neonatal life (a period of cellular differentiation of the reproductive tract, and a critical period of immune, behavioral, and adipocyte differentiation). These perinatal DES animal models have successfully duplicated, and in some cases, predicted, many of the alterations (structural, function, cellular and molecular) observed in similarly DES- exposed humans.

Although the data summarized in this review describes only neonatal exposure to a high dose of DES, lower doses and exposure during prenatal life have also been shown to be associated with obesity later in life. Interestingly, high prenatal DES doses caused lower birth weight compared to controls, followed by a “catch-up period”, and finally resulted in obesity; low prenatal DES doses had no effect on birth weight but it still resulted in obesity later in life . Thus, it appears that the effects of DES on adipocytes may depend on the time of exposure and the dose, and that multiple mechanisms maybe altered resulting in the same obesity phenotype.

Sources

Environmental Estrogens and Obesity, NCBI PMCID: PMC2682588, Retha R. Newbold,1 Elizabeth Padilla-Banks, and Wendy N. Jefferson, Mol Cell Endocrinol. Author manuscript; available in PMC 2010 May 25.