Melamine regulatory assessment for endocrine disruption.

Melamine has several domestic and industrial uses as a flame retardant or in the manufacture of melamine-formaldehyde resins. Based on available scientific literature data, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) included this substance in the list of "chemicals that may present endocrine disruptor (ED) properties", and the substance was prioritized to assess whether it should be classified as an ED in European Union (EU) regulations for hazard identification. This review reports the assessment of melamine based on relevant studies from the registration dossier under REACH, and peer-reviewed literature.

How to Differentiate General Toxicity-Related Endocrine Effects from Endocrine Disruption: Systematic Review of Carbon Disulfide Data.

This review provides an overview of the assessment of the endocrine disrupting (ED) properties of carbon disulfide (CS), following the methodology used at the European level to identify endocrine disruptors. Relevant in vitro, in vivo studies and human data are analyzed. The assessment presented here focuses on one endocrine activity, i.

Regulatory and academic studies to derive reference values for human health: The case of bisphenol S.

The close structural analogy of bisphenol (BP) S with BPA, a recognized endocrine-disrupting chemical and a substance of very high concern in the European Union, highlights the need to assess the extent of similarities between the two compounds and carefully scrutinize BPS potential toxicity for human health. This analysis aimed to investigate human health toxicity data regarding BPS, to find a point of departure for the derivation of human guidance values. A systematic and transparent methodology was applied to determine whether European or international reference values have been established for BPS.

Adipose-Tissue-Derived Mesenchymal Stem Cells Mediate PD-L1 Overexpression in the White Adipose Tissue of Obese Individuals, Resulting in T Cell Dysfunction.

The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT.

Impact of Estrogen Withdrawal and Replacement in Female Mice along the Intestinal Tract. Comparison of E2 Replacement with the Effect of a Mixture of Low Dose Pollutants.

Postmenopausal women represent a vulnerable population towards endocrine disruptors due to hormonal deficit. We previously demonstrated that chronic exposure of ovariectomized C57Bl6/J mice fed a high-fat, high-sucrose diet to a low-dose mixture of chemicals with one dioxin, one polychlorobiphenyl, one phthalate, and bisphenol A triggered metabolic alterations in the liver but the intestine was not explored. Yet, the gastrointestinal tract is the main route by which pollutants enter the body.

Endocrine disrupting chemicals and metabolic disorders in the liver: What if we also looked at the female side?

Endocrine disrupting chemicals (EDCs) are linked to the worldwide epidemic incidence of metabolic disorders and fatty liver diseases, which affects quality of life and represents a high economic cost to society. Energy homeostasis exhibits strong sexual dimorphic traits, and metabolic organs respond to EDCs depending on sex, such as the liver, which orchestrates both drug elimination and glucose and lipid metabolism. In addition, fatty liver diseases show a strong sexual bias, which in part could also originate from sex differences observed in gut microbiota.

Adipose Tissue and Endocrine-Disrupting Chemicals: Does Sex Matter?

Obesity and metabolic-related diseases, among which diabetes, are prominent public health challenges of the 21st century. It is now well acknowledged that pollutants are a part of the equation, especially endocrine-disrupting chemicals (EDCs) that interfere with the hormonal aspect. The aim of the review is to focus on adipose tissue, a central regulator of energy balance and metabolic homeostasis, and to highlight the significant differences in the endocrine and metabolic aspects of adipose tissue between males and females which likely underlie the differences of the response to exposure to EDCs between the sexes.

Exposure to pollutants altered glucocorticoid signaling and clock gene expression in female mice. Evidence of tissue- and sex-specificity.

Environmental pollutants suspected of disrupting the endocrine system are considered etiologic factors in the epidemic of metabolic disorders. As regulation of energy metabolism relies on the integrated action of a large number of hormones, we hypothesized that certain chemicals could trigger changes in glucocorticoid signaling. To this end, we exposed C57Bl6/J female and male mice between 5 and 20 weeks of age to a mixture of 2,3,7,8- tetrachlorodibenzo-p-dioxin (20 pg/kg body weight/day [bw/d]), polychlorobiphenyl 153 (200 ng/kg bw/d), di-[2-ethylhexyl]-phthalate (500 μg/kg bw/d) and bisphenol A (40 μg/kg bw/d).

Estrogen withdrawal and replacement differentially target liver and adipose tissues in female mice fed a high-fat high-sucrose diet: impact of a chronic exposure to a low-dose pollutant mixture.

Postmenopausal women may be at particular risk when exposed to chemicals especially endocrine disruptors because of hormonal deficit. To get more insight, ovariectomized C57Bl6/J mice fed a high-fat high-sucrose diet were chronically exposed from 5 to 20 weeks of age to a low-dose mixture of chemicals with one dioxin, one polychlorobiphenyl, one phthalate and bisphenol A. Part of the mice received as well E2 implants to explore the potential estrogenic dependency of the metabolic alterations.

Chronic exposure to a pollutant mixture at low doses led to tissue-specific metabolic alterations in male mice fed standard and high-fat high-sucrose diet.

Excessive consumption of industrialized food and beverages is a major etiologic factor in the epidemics of obesity and associated metabolic diseases because these products are rich in fat and sugar. In addition, they contain food contact materials and environmental pollutants identified as metabolism disrupting chemicals. To evaluate the metabolic impact of these dietary threats (individually or combined), we used a male mouse model of chronic exposure to a mixture of low-dose archetypal food-contaminating chemicals that was added in standard or high-fat, high-sucrose (HFHS) diet.

Effects of bisphenol A on metabolism and evidences of a mode of action mediated through endocrine disruption.

Based on rodent studies after prenatal and/or perinatal or adult exposure, there is now evidence that BPA may increase metabolic disturbances eventually leading to type-2 diabetes development via an ED MoA. In particular, BPA has been shown to alter insulin synthesis and/or release by pancreatic β-cells, and insulin signaling within insulin-sensitive organs (i.e.

Regulatory identification of BPA as an endocrine disruptor: Context and methodology.

BPA is one of the most investigated substances for its endocrine disruptor (ED) properties and it is at the same time in the center of many ED-related controversies. The analysis on how BPA fits to the regulatory identification as an ED is a challenge in terms of methodology. It is also a great opportunity to test the regulatory framework with a uniquely data-rich substance and learn valuable lessons for future cases.

Evidence for estrogeno-mimetic effects of a mixture of low-dose pollutants in a model of ovariectomized mice.

We recently hypothesized that a mixture of low-dosed dioxin, polychlorobiphenyl, phthalate and bisphenol may induce estrogeno-mimetic activities in a model of lifelong-exposed female mice. Herein, we evaluated the impact of this mixture in estrogen deficiency conditions. Based on the protective effects of estrogens against metabolic disorders, we reasoned that exposure to pollutants should attenuate the deleterious metabolic effects induced by ovariectomy.

Endocrine disrupting chemicals in mixture and obesity, diabetes and related metabolic disorders.

Obesity and associated metabolic disorders represent a major societal challenge in health and quality of life with large psychological consequences in addition to physical disabilities. They are also one of the leading causes of morbidity and mortality. Although, different etiologic factors including excessive food intake and reduced physical activity have been well identified, they cannot explain the kinetics of epidemic evolution of obesity and diabetes with prevalence rates reaching pandemic proportions.

Low-dose pollutant mixture triggers metabolic disturbances in female mice leading to common and specific features as compared to a high-fat diet.

Environmental pollutants are potential etiologic factors of obesity and diabetes that reach epidemic proportions worldwide. However, it is important to determine if pollutants could exert metabolic defects without directly inducing obesity. The metabolic disturbances triggered in nonobese mice lifelong exposed to a mixture of low-dose pollutants (2,3,7,8-tetrachlorodibenzo-p-dioxine, polychlorinated biphenyl 153, diethylhexyl-phthalate, and bisphenol A) were compared with changes provoked by a high-fat high-sucrose (HFHS) diet not containing the pollutant mixture.

[Impact of in utero exposure to pollutants on metabolic health in adults].

Obesity is a major public health problem because it is a risk factor for metabolic disorders including type 2 diabetes and cardiovascular disorders. Notably, pollutants endowed with endocrine disrupting activities have been charged to contribute to the etiology of obesity and type 2 diabetes, especially if exposure occurs during the early life shown to be a highly vulnerable window of time. An overview on endocrine disrupters in relation with the obesogen and metabolic disruption hypothesis is presented.

Metabolic outcome of female mice exposed to a mixture of low-dose pollutants in a diet-induced obesity model.

Pollutants are suspected to contribute to the etiology of obesity and related metabolic disorders. Apart from occupational exposure which concerns a subset of chemicals, humans are mostly exposed to a large variety of chemicals, all life-long and at low doses. Food ingestion is a major route of exposure and it is suggested that pollutants have a worsened impact when combined with a high-fat diet.

Low-dose food contaminants trigger sex-specific, hepatic metabolic changes in the progeny of obese mice.

Environmental contaminants are suspected to be involved in the epidemic incidence of metabolic disorders, food ingestion being a primarily route of exposure. We hypothesized that life-long consumption of a high-fat diet that contains low doses of pollutants will aggravate metabolic disorders induced by obesity itself. Mice were challenged from preconception throughout life with a high-fat diet containing pollutants commonly present in food (2,3,7,8-tetrachlorodibenzo-p-dioxin, polychlorinated biphenyl 153, diethylhexyl phthalate, and bisphenol A), added at low doses in the tolerable daily intake range.

Direct and indirect impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on adult mouse Leydig cells: an in vitro study.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related substances are ubiquitous environmental pollutants that exert adverse effects on reproductive processes. In testis, Leydig cells which produce testosterone are under hormonal and local control exerted by cytokines including TNFα. Using mouse Leydig primary cell cultures as a model, we studied the effects of TCDD on the steroidogenic outcome of Leydig cells and the gene expression levels of Ccl5 and Cxcl4, previously shown to be target genes of TCDD in testis.

Chronic consumption of farmed salmon containing persistent organic pollutants causes insulin resistance and obesity in mice.

Background: Dietary interventions are critical in the prevention of metabolic diseases. Yet, the effects of fatty fish consumption on type 2 diabetes remain unclear. The aim of this study was to investigate whether a diet containing farmed salmon prevents or contributes to insulin resistance in mice.

Phenotyping the claudin 11 deficiency in testis: from histology to immunohistochemistry.

The testis is a heterogeneous organ that comprises a number of cell types, including germ cells at -different stages in their maturation, differentiated neighbor nursing cells, and endocrine somatic cells. Despite such cellular heterogeneity the testis is highly organized, with germ cell development and differentiation being compartmentalized into the interconnected tubular network of the seminiferous epithelium. Intratesticular scaffolds rely heavily on the basement membrane of the seminiferous tubules while germ cell development inside the seminiferous epithelium is critically dependent on the Blood Testis Barrier (BTB).