Endocrine modulators in the food chain and environment


Recently, considerable attention has been focused on certain environmental contaminants–“endocrine disruptors”–of industrial origin that may mimic the action of sex hormones. Natural compounds and their effects on other types of hormonal activity (eg, on adrenal or thyroid function) have for some reason not provoked similar attention.

As exemplified by tributyltin and certain bioaccumulating chlorinated compounds, available evidence indicates that “endocrine disruption” caused by xenobiotics is primarily an ecotoxicologic problem.

In mammals, certain phenylmethyl-substituted siloxanes have been found to be by far the most potent endocrine disrupters among various synthetic xenobiotics.

On the other hand, it has not been possible to scientifically substantiate either certain alarming reports of powerful synergistic effects between chlorinated pesticides or the alleged adverse effects on the male reproductive tract in rodents (induced by alkylphenols and plasticizers at extremely low exposures).

Whereas there is compelling evidence that estrogens in certain foods and herbal medicines can induce hormonal changes in women as well as overt toxicity in men, existing data are insufficient to support a causal relationship between exposure of the general human population to nonpharmaceutical industrial chemicals and adverse effects operating via the endocrine system.

Moreover, in terms of magnitude and extent, all such exposures to so-called endocrine disruptors are dwarfed by the extensive use of oral contraceptives and estrogens for treatment of menopausal and postmenopausal disorders.

Also, the exposure to hormonally active xenobiotics is virtually insignificant when compared with the intake of the phytoestrogens that are present in food and beverages, and it is even more insignificant when compared with certain herbal potions used in “alternative medicine.”

Furthermore, while there has been much concern about negligible exposures to xenobiotics with weak hormonelike activities, the potent endocrine disruptor licorice is freely given to children. Long-term exposure to this substance induces severe toxic symptoms of mineral corticoid hormone imbalance.

Although exposures to xenobiotics and many natural compounds occur by identical routes of administration and may contribute to the same toxicological end point, they are, regrettably, judged by completely different standards. As is the case with all other chemicals, rational risk assessment and risk management of man-made and natural endocrine modulators must be based on the mode of action and dose-response relationships. Such end points as the induction of reproductive developmental effects, cancer, etc, relating to actual exposures must also be taken into consideration.


…”Whereas the xenobiotic endocrine modulators usually show very little structural resemblance with the natural hormones, many phytoestrogens and, to a lesser extent, the potent synthetic estrogen diethylhexylstilbestrol and the mycotoxin zearalenone have molecular configurations that are akin to mammalian sex hormones.”…

…”A systematic survey demonstrated that the highest activity was exhibited by 2.6-cis-diphenylhexamethyl cyclotetrasiloxane and phenylheptamethyl cyclotetrasiloxane, which exhibited a potency of about 1/10th of that of diethylstilbestrol ie, orders of magnitude higher than that for other xenoestrogens. These compounds also have the capacity to accumulate in brown fat, lung, liver, spleen, and adrenal cortex in the rodent.”…

…”Structural activity considerations would predict a much lower biological activity for the xenobiotic endocrine modulators than for the natural phytoestrogens. The high potency of diethylstilbestrol is somewhat less apparent from the chemical structure, and for 2,6-cis-diphenylhexamethyl cyclotetrasiloxane, this is even less so. “…


  • Endocrine modulators in the food chain and environment, Toxicologic Pathology, NCBI PubMed PMID: 10862560, 2000 May-Jun.
  • Image credit kut.

Possible links to the development of obesity

Diethylstilboestrol—A long-term legacy, School of Biosciences, 2012


Obesity and type 2 diabetes levels have risen over the past century, the incidence being more marked in recent years. Both these conditions have adverse consequences and are significant public health issues. Even pets, laboratory animals and urban rats have increased in average body weight over the past decades. These trends in both humans and animals are not necessarily explicable by diet and exercise; prenatal exposure to environmental triggers (‘obesogens’), has been suggested as a possible factor, particularly to oestrogenic compounds such as DES, bisphenol A and phthalates.

Adipose tissue acts as an endocrine organ, releasing
hormones controlling appetite and energy metabolism and is a site for oestrogen synthesis. This mechanism, found in both animals and human beings, ensures a link between the food supply and the capacity to reproduce, since starvation and pregnancy are not a good combination. When low doses of DES were administered to mice pre- or neo-natally, the adult animals gained weight with altered expression of obesity-related genes and altered hormone levels. There was no difference in the number of fat cells but the cells already present increased in size.

Although it is not known at present whether DES acts as an obesogen in man, raised urinary concentrations of other environmental chemicals, such as phthalates, have been linked with the increased body weight and insulin resistance which lead to ‘metabolic syndrome’.



Obesogenic endocrine disruptors and obesity

Myths and truths, Archives of Toxicology, 2017


Obesogenic endocrine disruptors, also known as obesogens, are chemicals potentially involved in weight gain by altering lipid homeostasis and promoting adipogenesis and lipid accumulation. They included compounds to which human population is exposed over daily life such as pesticides/herbicides, industrial and household products, plastics, detergents and personal care products.

The window of life during which the exposure happens could lead to different effects. A critical window is during utero and/or neonatal period in which the obesogens could cause subtle changes in gene expression and tissue organization or blunt other levels of biological organization leading to increased susceptibility to diseases in the adulthood.

“…the exposure to diethylstilbestrol (DES) during neonatal period resulted in increased body weight.
Interestingly, this efect was specifc for females and did not appear until 4–6 months. In male mice, the exposure to DES was accompanied by an increased number of adipocytes in the gonadal fat pad of mice.” …

… “…the prenatal exposure to DES resulted in childhood obesity at age of 7 and increased risk of adult obesity.”

Some of the reasons for this increased sensitivity include the lack of the protective mechanisms that are available in adult such as DNA repair mechanisms, a competent immune system, detoxifying enzymes, liver metabolism and the blood/brain barrier still not fully functional in the fetus or newborn.

The mechanisms of action of obesogens lay on their ability to increase the number and/or the size of the adipocytes and to alter appetite, satiety and food preferences.

The ability of obesogens to increase fat deposition results in an increased capacity for their own retention due to their lipophilic properties; thus prolonging the exposure and increasing the detrimental metabolic consequences.


  • Obesogenic endocrine disruptors and obesity: myths and truths, Archives of Toxicology, NCBI PubMed PMID: 28975368, 2017 Nov.
  • Image credit Siora Photography.

Etiology of obesity : Environmental Estrogen DES

DES exposure effects in mouse models replicate human findings

Abstract from “EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals”, 2015

Obesity requires eating more food and/or consuming less energy. To date, most of the obesity studies in animals are based in the observation that EDC exposures induce weight increases and changes in adiposity, as well as affecting hormones and adipokines involved in the regulation of food intake and energy expenditure. There are fewer studies related to how EDCs disrupt energy balance. Therefore, more studies are necessary to gain mechanistic insights into the role that EDCs play in the etiology of obesity.

Studies of rodents that were prenatally, neonatally, or perinatally exposed to EDCs support the obesogen hypothesis. For example, DES exposure effects in mouse models replicate human findings. DES is an estrogenic chemical that binds with high affinity to the ERs, ERα and ERβ, which play an important role in adiposity regulation as well as central and peripheral energy balance. Developmental exposure to DES in mice induced adipogenesis and caused mice to become obese or overweight.

Other chemicals classified as environmental estrogens, particularly BPA, produced similar effects. Perinatal exposure to low doses of BPA caused increased body weight; adiposity; alterations in blood levels of insulin, leptin, and adiponectin; as well as a decrease in glucose tolerance and insulin sensitivity in an age-dependent manner.



Environmental Estrogens, Obesity, and Metabolism

Perinatal exposure to DES and latent development of high body weight and obesity

Abstract from “Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement”, 2009

White adipose tissue metabolism is under the control of the sympathetic nervous system and is modulated by hormones including sex steroids. The impact of environmental estrogens on adipose tissue may be through direct modulation of lipogenesis, lipolysis, and adipogenesis, or indirect by affecting food consumption and leptin secretion targeting the central nervous system or lipid homeostasis in liver.

The estrogenic pharmaceutical chemical DES illuminates the relationship between perinatal exposures and latent development of high body weight and obesity. Moreover, there is a complex relationship between the concentration of estrogen to which pregnant animals are exposed and the weight of the offspring in adulthood. Specifically, according to a recent experiment by Newbold et al., mice neonatally exposed to DES experience increased body weight in adulthood associated with excess abdominal body fat. Interestingly, the dose of DES determines the chronic manifestation of the observed alterations, with high doses leading to initially decreased body weight and a peripubertal “catch-up” and low doses causing an increase in weight detectable only in adulthood. Moreover, the timing is important because gestational administration in rodents results in the offspring’s low birth weight, an unchanged metabolic characteristic throughout life. Along with an increase in body fat stores, the adipokines leptin and adiponectin, IL-6 (an inflammatory marker), and triglycerides were all elevated in DES-exposed mice.

An in vitro study using a culture system of 3T3-L1 preadipocytes showed that 4-nonylphenol and BPA stimulated lipid accumulation, accelerating their differentiation to mature adipocytes in a time- and concentration-dependent way. The underlying mechanism appeared to involve up-regulation of gene expression involved in lipid metabolism and adipocyte differentiation. In the second part of the experiment, fat accumulation was observed in human hepatocellular carcinoma cell lines exposed to those endocrine disruptors. These findings are consistent with previous in vitro studies using mouse fibroblast cell lines in which a link between environmental chemicals including nonylphenol, BPA, and genistein in the development of body weight imbalance was suggested.


  • Full study (free access) : Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement, Endocrine Society endocrine reviews, PMC2726844, 2009 Jun.

Pharmacologic sex hormones in pregnancy in relation to offspring obesity

2014 Study objective : to assess the association between in utero exposure to either diethylstilbestrol (DES) or an oral contraceptive in pregnancy and offspring obesity

What is already known about this subject

  • In animal models, in utero exposure to exogenous estrogenic agents is associated with offspring adiposity.
  • In in vitro and animal models, diethylstilbestrol exposure has led to an increase in stem cell differentiation into preadipocytes and adipocytes.

What this study adds

  • An evaluation of the association between in utero exposure to pharmacologic estrogens and subsequent obesity in humans.
  • A novel approach to studying the potential for developmental origins of obesity as conferred through in utero exposure to estrogenic agents.


Using data from the Collaborative Perinatal Project (1959-1974), a multicenter prospective study of pregnant women and their offspring, we examined overweight or obesity among 34,419 children with height and weight data at age 7 years. Generalized linear models to estimate the adjusted odds ratio (aOR) for overweight or obesity (≥85th percentile) or obesity (≥95th percentile) in the offspring according to exposure during different months of pregnancy were used.

Oral contraceptive use during pregnancy was positively associated with offspring overweight or obesity and obesity. The magnitude of association was strongest in the first 2 months of pregnancy for obesity (aOR 2.0, 95% CI: 1.1, 3.7). DES use was also associated with offspring overweight or obesity and obesity, with the association being strongest for exposure beginning between months 3 and 5 (e.g., for exposure beginning in months 3-4, the aOR for obesity was 2.8, 95% CI: 1.3, 6.3).

Pharmacologic sex hormone use in pregnancy may be associated with childhood obesity. Whether contemporary, lower dose oral contraceptive formulations are similarly associated with increased risk of childhood obesity is unclear.


  • Full study (free access) : Pharmacologic sex hormones in pregnancy in relation to offspring obesity, Obesity (Silver Spring), PMID: 20688618, 2014 Nov.
  • Featured image i yunmai.

Impact of environmental endocrine disrupting chemicals on the development of obesity

Developmental effects of diethylstilbestrol DES on obesity

2010 Review Abstracts

Environmental chemicals with hormone-like activity can disrupt programming of endocrine signaling pathways during development and result in adverse effects, some of which may not be apparent until much later in life. Recent reports link exposure to environmental endocrine disrupting chemicals during development with adverse health consequences, including obesity and diabetes. These particular diseases are quickly becoming significant public health problems and are fast reaching epidemic proportions worldwide. This review summarizes data from experimental animals and humans which support an association of endocrine disrupting chemicals, such as diethylstilbestrol, bisphenol A, phytoestrogens, phthalates, and organotins, with the development of obesity. Potential mechanisms are summarized and future research needs are discussed.

Also, the developing fetus and neonate have increased metabolic rates as compared to adults which in some cases may make them more vulnerable to chemical toxicity. It is now well established in the fields of nutrition and endocrine disruption that exposure to environmental chemicals during development can interfere with complex differentiating endocrine signaling pathways and cause adverse consequences later in life; the well known reproductive tract toxicity of diethylstilbestrol (DES) is one of the best examples of adverse consequences of endocrine disrupting chemicals. The concept of the “developmental origins of adult disease”, as the term implies, suggests that there is a time lag between exposure and manifestation of disease. In other words, the effects of exposure during development may not be readily apparent until much later in life.

DES, a potent synthetic estrogen, was widely prescribed to pregnant women from the 1940s through the 1970s in 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 exposure resulted in a low but significant increase in neoplastic lesions and a high incidence of benign lesions in both the male and female offspring. The DES paradigm was a clear example that prenatal exposure could lead to adult-onset disease. To study the mechanisms involved in DES toxicity, we developed experimental mouse models of perinatal (prenatal or neonatal) DES exposure in which outbred mice were treated with DES 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, functional, cellular, and molecular) observed in similarly DES-exposed humans. Further, these models have also shown multigenerational transmission of disease patterns implicating epigenetic mechanisms in the transmission of these effects.

Although our initial focus was on reproductive tract abnormalities and subfertility/infertility, we subsequently examined the relationship of perinatal DES treatment with the development of obesity later in life. We wanted to determine if DES was an “obesogen” as well as a reproductive toxicant and, if so, what were its molecular targets and the mechanisms through which it might act. For our obesity experiments, mice were treated with DES on days 1-5 of neonatal life using a low dose of 0.001 mg/day (1 µg/kg/day); this dose did not affect body weight during treatment but was associated with a significant increase in body weight in the adult animal by 4 to 6 months of age; male mice treated as neonates did not have an increase in body weight.

Unlike the low dose of DES (0.001 mg/day = 1 µg/kg/day), a higher dose (1000 µg/kg/day =1 mg/kg/day) caused a significant decrease in body weight during treatment but it was followed by a “catch-up” period around puberty and then finally resulted in an increase in body weight of the DES-treated mice compared to controls after ~2 months of age. This “catch-up” in weight between treated and control animals is reminiscent of the thrifty phenotype which is a well known phenomenon in the field of nutrition and was described in human infants who received poor nutrition during fetal life but later had “catch-up” growth that finally resulted in overweight and obesity later in life. Further studies indicated that the increase in body weight in DES-exposed mice was associated with an increase in the percent of body fat as determined by mouse densitometry.

Increased body weight in both low and high DES-treated mice compared to controls was observed throughout adulthood; however, by 18 months of age, statistical differences in body weight between DES-treated mice and controls were difficult to show because individual animal variability within groups increased as they aged due to the altered health status of the DES animals. We concluded that since various doses of DES resulted in obesity whether or not pups were underweight during treatment, multiple pathways might be involved in the programming for obesity related to environmental estrogens.
Since densitometry images of DES-treated mice suggested excessive abdominal fat, specific fat pads were weighed to see if particular fat pads were affected by DES treatment or whether there was a generalized change throughout the mouse, since it is well known that increased abdominal fat is associated with cardiovascular disease and diabetes in humans. Weights of inguinal, parametrial, gonadal, and retroperitoneal fat pads were all increased in DES treated mice as compared to controls at 6-8 months of age, suggesting a potential impact on cardiovascular disease following developmental exposure to DES. Brown fat weights were not significantly different in these animals.

Examination of DES-treated mice (1000 µg/kg/day =1 mg/kg/day) and controls at 2 months of age, prior to the treated mice becoming overweight and obese, showed elevated serum levels of leptin, adiponectin, IL-6, and triglycerides, suggesting that these endpoints may be important early markers of subsequent adult disease. Elevated levels of leptin are not surprising considering the increase number and size of the adipocytes in the DES-treated mice, but the increase in adiponectin was not expected since low levels usually correlate with obesity and diabetes in humans. This may indicate insensitivity to these hormones and/or a loss of the negative feedback mechanisms that regulate adipogenesis. Nevertheless, additional studies are needed to determine the mechanisms involved. At 6 months of age, insulin and all of the serum markers except triglycerides were found to be significantly elevated as compared to controls.

Glucose levels were also measured in DES (1000 µg/kg/day =1 mg/kg/day) and control mice at 2 months of age prior to the development of obesity and excessive weight gain. Interestingly, 25% of the DES-treated mice had significantly higher glucose levels than controls; these mice also showed a slower clearance rate of glucose from the blood since higher levels were seen throughout the experiment. Additional glucose measurements in older mice may help determine if a higher percentage of mice are affected with age and if higher and sustained levels of glucose can be demonstrated. To date, our data suggest that overweight and obesity observed in perinatal DES-treated mice will be associated with the development of diabetes, similar to the association of obesity with diabetes in humans. Further studies from our laboratory support a role for altered glucose metabolism as we have shown a high prevalence of islet cell hyperplasia in mice exposed to DES or other environmental estrogens including BPA and genistein.

Since the imbalance of activity levels and food intake are known contributors to obesity, ambulatory activity was measured in DES (1000 µg/kg/day =1 mg/kg/day) and control mice at 2 months of age before a difference in body weight could be detected. Overall, no statistical difference could be shown in activity between groups, although the DES group showed slightly less movement as compared to controls. This slight difference was not sufficient to explain the enhanced weight gain in DES mice as they aged.

Food consumption was also assessed; DES-treated mice consumed more than controls over the course of the experiment (~3 grams more), but the amounts were not statistically different between the groups. Taking into account both the marginal decrease in activity and the increase in food intake in DES-treated mice as compared to controls, it is unlikely that these two parameters can solely explain the development of obesity in DES-treated mice.

A recent study indicated a role for developmental genes in the origins of obesity and body fat distribution in mice and humans. We examined whether exposure to environmental chemicals which exerted hormonal activity would alter expression of genes involved in programming adipocytes during development. Several genes were found to be implicated in altered adipocyte differentiation and function (Hoxa5, Gpc4, and Tbx15) as well as fat cell distribution (Thbd, Nr2f1, and Sfrp2). We investigated changes in gene expression by microarray analysis in uterine samples from DES-treated mice (1000 µg/kg/day =1 mg/kg/day) compared to controls at 19 days of age. Genes involved in adipocyte differentiation were not different in the uterus following neonatal DES exposure. However, genes involved in fat distribution were altered; Thbd and Nr2f1 were significantly down-regulated and Sfrp2 was significantly up-regulated in DES-treated uteri compared to controls. These findings support the idea that environmental estrogens may play a role in regulating the expression of obesity-related genes in development. The identification of genes and molecular mechanisms that may be associated with EDCs and obesity is an exciting area of new research.

Although only neonatal exposure to DES has been discussed thus far in this review, exposure during prenatal life has 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”, finally resulting 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 may be altered and result in the same obesity phenotype. Other investigators have also reported analogous findings with DES and other estrogenic chemicals.


  • Full study (free access) : Impact of environmental endocrine disrupting chemicals on the development of obesity, Hormones, PMID: 20688618, 2010 Jul-Sep.
  • Featured image PMC1931509/figure/F6.

Perinatal exposure to DES linked to obesity increase in a sex-dependent manner

The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice

2012 Study Abstract

Epidemiology studies indicate that exposure to endocrine disruptors during developmental “window” contributes to adipogenesis and the development of obesity.

Implication of endocrine disruptor such as diethylstilbestrol (DES) on adipose tissue development has been poorly investigated.

Here we evaluated the effects of DES on adipocyte differentiation in vitro and in vivo, and explored potential mechanism involved in its action.

DES induced 3T3-L1 preadipocyte differentiation in a dose-dependent manner, and activated the expression of estrogen receptor (ER) and peroxisome proliferator-acivated receptor (PPAR) γ as well as its target genes required for adipogenesis in vitro. ER mediated the enhancement of DES-induced PPARγ activity. Moreover, DES perturbed key regulators of adipogenesis and lipogenic pathway in vivo.

In utero exposure to low dose of DES significantly increased body weight, liver weight and fat mass in female offspring at postnatal day (PND) 60. In addition, serum triglyceride and glucose levels were also significantly elevated.

These results suggest that perinatal exposure to DES may be expected to increase the incidence of obesity in a sex-dependent manner and can act as a potential chemical stressor for obesity and obesity-related disorders.


  • The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice, Toxicology and applied pharmacology, PMID: 22710028, 2012.
  • Featured image trbimg.

Endocrine disruptors and obesity: obesogens

Developmental effects of diethylstilbestrol and other EDCs on obesity


Incidence and prevalence of owerweight and obesity have greatly increased over the past three decades in almost all countries around the world.

This phenomenon is not easily explained by lifestyle changes in populations with very different initial habits. This has led to consider the influence of other factors, the so-called endocrine disruptors, and more specifically obesogens.

This study reviewed the available evidence about polluting chemical substances which may potentially be obesogens in humans: DES, genistein, bisphenol A, organotins (TBT, TPT), and phthalates. The first three groups of substances mainly act upon estrogen receptors, while organotins and phthalates activate PPARγ.

It was concluded that evidence exists of the obesogenic effect of these chemical substances in tissues and experimental animals, but few data are available in humans.



Developmental effects of diethylstilbestrol and other EDCs on obesity

Developmental exposure to endocrine-disrupting chemicals programs for reproductive tract alterations and obesity later in life


Many chemicals in the environment, especially those with estrogenic activity, are able to disrupt the programming of endocrine signaling pathways established during development; these chemicals are referred to as endocrine-disrupting chemicals. Altered programming can result in numerous adverse consequences in estrogen-target tissues, some of which may not be apparent until later in life. For example, a wide variety of structural, functional, and cellular effects have been identified in reproductive tract tissues. In addition to well-documented reproductive changes, obesity and diabetes have joined the list of adverse effects that have been associated with developmental exposure to environmental estrogens and other endocrine-disrupting chemicals.

Obesity is a significant public health problem reaching epidemic proportions worldwide. Experimental animal studies document an association of developmental exposure to environmental estrogens and obesity. For example, a murine model of perinatal exposure to diethylstilbestrol has proven useful in studying mechanisms involved in abnormal programming of differentiating estrogen-target tissues, including reproductive tract tissues and adipocytes. Other environmental estrogens, including the environmental contaminant bisphenol A, have also been linked to reproductive problems and obesity later in life. Epidemiology studies support similar findings in humans, as do studies of cells in culture.

Together, these findings suggest new targets for abnormal programming by estrogenic chemicals and provide evidence supporting the scientific concept termed the developmental origins of adult disease. Furthermore, the association of environmental estrogens with obesity and diabetes expands the focus on these diseases from intervention or treatment to include prevention or avoidance of chemical modifiers, especially during critical windows of development.

Developmental effects of diethylstilbestrol and other EDCs on obesity

Obesity and overweight have dramatically increased in prevalence in wealthy industrialized countries over the past 2 to 3 decades and also in poorer underdeveloped nations, where it often coexists with undernutrition. Obesity has now reached epidemic proportions in the United States, although a recent study found that its increase has stopped its upward spiral in the past few years; however, there is no indication of any decreases in prevalence. Common causes of obesity have usually been attributed to high-calorie, high-fat diets and a lack of exercise combined with a genetic predisposition for the disease. However, the current alarming rise in obesity cannot be solely explained by only these factors; an environmental component must be involved. It has been suggested that exposure to EDCs during critical stages of adipogenesis is contributing to the obesity epidemic. The term obesogens has been coined for environmental chemicals that stimulate fat accumulation, referring to the idea that they inappropriately regulate lipid metabolism and adipogenesis to promote obesity.

Experimental animal studies support the idea of involvement of EDCs in obesity; developmental exposure to numerous chemicals — including diethylstilbestrol, other estrogens, and other chemicals, such as tributyl tin — has been associated with obesity or overweight and adipogenesis. Recently, there has been much interest in the chemical bisphenol A (BPA) because of its high production volume and its potential for widespread environmental contamination. Numerous studies have now shown an association of BPA exposure with increased body weight and adiposity. The later study suggests that an increase in body weight is sex specific, but that timing and dose may contribute to the complexity of these findings because other investigators report effects in both males and females. Interestingly, a recent article describes similar increases, as previously reported, in the body weights of pups obtained from moms fed BPA in their diets during pregnancy; the doses were low and were considered “ecologically relevant” at 1 μg BPA/kg diet (1 ppb). However, unlike previous reports, the differences in body weight at weaning disappear as the mice age. This is probably due to the palatability of the diet, which was substituted at weaning because both control and BPA mice did not continue to gain weight on the new diets.

In vitro studies with BPA provide additional evidence of a role for this chemical in the development of obesity and further suggest specific targets; BPA causes 3T3-L1 cells (mouse fibroblast cells that can differentiate into adipocytes) to increase differentiation and, in combination with insulin, accelerates adipocyte formation. Other in vitro studies have shown that low doses of BPA, similar to diethylstilbestrol, impair calcium signaling in pancreatic α cells, disrupt β cell function, and cause insulin resistance (48, 49). Low environmentally relevant doses of BPA have also been reported to inhibit adiponectin and stimulate the release of inflammatory adipokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), from human adipose tissue, which suggests that BPA is involved in obesity and the related metabolic syndrome. Furthermore, other studies have linked BPA exposure to disruption of pancreatic β cell function and blood glucose homeostasis in mice, which suggests changes indicative of the metabolic syndrome.

Epidemiologic studies also support an association of BPA with obesity. BPA was detected at higher concentrations in both nonobese and obese women with polycystic ovarian syndrome than in nonobese healthy women, which suggests the possible involvement of BPA in polycystic ovarian syndrome and/or obesity.


  • Full study (free access) : Developmental exposure to endocrine-disrupting chemicals programs for reproductive tract alterations and obesity later in life, The American journal of clinical nutrition, PMC3364077, 2011 Dec.
  • Featured image Sandra Cohen-Rose and Colin Rose..