As breast cancer incidence continues to rise worldwide, there is a pressing need to understand the environmental factors that contribute to its development. Obesogens, including Bisphenol A (BPA) and Dichlorodiphenyltrichloroethane (DDT), are highly prevalent in the environment, and have been associated with obesity and metabolic dysregulation. BPA and DDT, known to disrupt hormone signaling in breast epithelial cells, also promote adipogenesis, lipogenesis, and adipokine secretion in adipose tissue, directly contributing to the pathogenesis of obesity. While the adipose-rich mammary gland may be particularly vulnerable to environmental obesogens, there is a scarcity of research investigating obesogen-mediated changes in adipocytes that drive oncogenic transformation of breast epithelial cells. Here, we review the preclinical and clinical evidence linking BPA and DDT to impaired mammary gland development and breast cancer risk. We discuss how the obesogen-driven mechanisms that contribute to obesity, including changes in adipogenesis, lipogenesis, and adipokine secretion, could provide a pro-inflammatory, nutrient-rich environment that promotes activation of oncogenic pathways in breast epithelial cells. Understanding the role of obesogens in breast cancer risk and progression is essential for informing public health guidelines aimed at minimizing obesogen exposure, to ultimately reduce breast cancer incidence and improve outcomes for women.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. CVDs are promoted by the accumulation of lipids and immune cells in the endothelial space resulting in endothelial dysfunction. Endothelial cells are important components of the vascular endothelium, that regulate the vascular flow. The imbalance in the production of vasoactive substances results in the loss of vascular homeostasis, leading the endothelial dysfunction. Thus, endothelial dysfunction plays an essential role in the development of atherosclerosis and can be triggered by different cardiovascular risk factors. On the other hand, the 17β-estradiol (E2) hormone has been related to the regulation of vascular tone through different mechanisms. Several compounds can elicit estrogenic actions similar to those of E2. For these reasons, they have been called endocrine-disrupting compounds (EDCs). This review aims to provide up-to-date information about how different EDCs affect endothelial function and their mechanistic roles in the context of CVDs.

Excess body weight constitutes one of the major health challenges for societies and healthcare systems worldwide. Besides the type of diet, calorie intake and the lack of physical exercise, recent data have highlighted a possible association between endocrine-disrupting chemicals (EDCs), such as bisphenol A, phthalates and their analogs, and obesity. EDCs represent a heterogeneous group of chemicals that may influence the hormonal regulation of body mass and adipose tissue morphology. Based on the available data from mechanistic, animal and epidemiological studies including meta-analyses, the weight of evidence points towards the contribution of EDCs to the development of obesity, associated disorders and obesity-related adipose tissue dysfunction by (1) impacting adipogenesis; (2) modulating epigenetic pathways during development, enhancing susceptibility to obesity; (3) influencing neuroendocrine signals responsible for appetite and satiety; (4) promoting a proinflammatory milieu in adipose tissue and inducing a state of chronic subclinical inflammation; (5) dysregulating gut microbiome and immune homeostasis; and (6) inducing dysfunction in thermogenic adipose tissue. Critical periods of exposure to obesogenic EDCs are the prenatal, neonatal, pubertal and reproductive periods. Interestingly, EDCs even at low doses may promote epigenetic transgenerational inheritance of adult obesity in subsequent generations. The aim of this review is to summarize the available evidence on the role of obesogenic EDCs, specifically BPA and phthalate plasticizers, in the development of obesity, taking into account in vitro, animal and epidemiologic studies; discuss mechanisms linking EDCs to obesity; analyze the effects of EDCs on obesity in critical chronic periods of exposure; and present interesting perspectives, challenges and preventive measures in this research area.

Bisphenol A (BPA) is a xenobiotic with endocrine disruptor properties which interacts with various receptors, eliciting a cellular response. In the plastic industry, BPA is widely used in the production of polycarbonate and epoxy-phenolic resins to provide elastic properties. It can be found in the lining of canned foods, certain plastic containers, thermal printing papers, composite dental fillings, and medical devices, among other things. Therefore, it is a compound that, directly or indirectly, is in daily contact with the human organism. BPA is postulated to be a factor responsible for the global epidemic of obesity and non-communicable chronic diseases, belonging to the obesogenic and diabetogenic group of compounds. Hence, this endocrine disruptor may be responsible for the development of metabolic disorders, promoting in fat cells an increase in proinflammatory pathways and upregulating the expression and release of certain cytokines, such as IL6, IL1β, and TNFα. These, in turn, at a systemic and local level, are associated with a chronic low-grade inflammatory state, which allows the perpetuation of the typical physiological complications of obesity.

Bisphenols, parabens (PBs), and benzophenones (BPs) are widely used environmental chemicals that have been linked to several adverse health effects due to their endocrine disrupting properties. However, the cellular pathways through which these chemicals lead to adverse outcomes in humans are still unclear, suggesting some evidence that inflammation might play a key role. Thus, the aim of this study was to summarize the current evidence on the relationship between human exposure to these chemicals and levels of inflammatory biomarkers. A systematic review of peer-reviewed original research studies published up to February 2023 was conducted using the MEDLINE, Web of Science, and Scopus databases. A total of 20 articles met the inclusion/exclusion criteria. Most of the reviewed studies reported significant associations between any of the selected chemicals (mainly bisphenol A) and some pro-inflammatory biomarkers (including C-reactive protein and interleukin 6, among others). Taken together, this systematic review has identified consistent positive associations between human exposure to some chemicals and levels of pro-inflammatory biomarkers, with very few studies exploring the associations between PBs and/or BPs and inflammation. Therefore, a larger number of studies are required to get a better understanding on the mechanisms of action underlying bisphenols, PBs, and BPs and the critical role that inflammation could play.

Metabolic syndrome (MS) is a multifactorial disease entity and is not fully understood. Growing evidence suggests that early exposure to bisphenol A (BPA) is a significant risk factor for the development of metabolic diseases. BPA is a monomer used in the manufacturing of polycarbonate plastics, thermal receipt paper, and epoxy resins. Owing to its widespread use, BPA has been detected in human fluids and tissues, including blood, placental breast milk, and follicular fluid. In the present review, we aimed to review the impact of prenatal exposure to different doses of BPA on metabolic parameters as determined by in vivo and epidemiological studies. The PubMed, Scopus, and Web of Science electronic databases were searched to identify articles published during a period of 15 years from 2006 to 2021, and 29 studies met the criteria. Most studies demonstrated that prenatal exposure to low BPA concentrations correlated with alterations in metabolic parameters in childhood and an increased risk of metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM), in adulthood. Therefore, prenatal exposure to low doses of BPA may be associated with an increased risk of obesity and T2DM in a sex-specific manner.

Exposure to endocrine disrupting chemicals (EDCs) may lead to dysregulated inflammatory responses, however, the detailed relationship between different EDCs and inflammation remains unclear. A systematic review and meta-analysis was conducted to evaluate the associations between four types of EDCs (bisphenol A (BPA), phthalates (PAEs), organochlorine pesticides (OCPs), and polychlorinated biphenyls (PCBs)) and markers of inflammation and immune responses in humans. Three databases were searched, and 36 studies with a total of 22055 participants were included. The associations between EDCs and 26 inflammation-related acute phase proteins and cytokines were analyzed. The results demonstrated that exposure to BPA was positively associated with circulating levels of C-reactive protein (CRP) and interleukin (IL)-6. Exposure to PAEs was associated with elevated levels of CRP, IL-6 and IL-10. Subgroup analysis found that three PAE metabolites mono-benzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) were directly associated with a higher level of CRP, and two other PAE metabolites mono-carboxyisononyl phthalate (MCNP) and mono-3-carboxypropyl phthalate (MCPP) were positively associated with IL-6. The positive associations between PAEs and CRP, IL-6 and IL-10 were significant in the high-molecular-weight phthalate (HMWP) exposure group, not the low-molecular-weight phthalate (LMWP) exposure group. Exposure to OCPs was positively associated with CRP, IL-1β, IL-2, and IL-10. No significant association was found between PCBs and inflammatory markers. These findings demonstrate that exposure to EDCs is closely linked to dysregulated inflammatory responses. More studies should be conducted in the future to get a comprehensive view of the associations between different EDCs and inflammation, and investigations on the underlying mechanisms are needed.