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Chemical structure of some plasticizers. DEHP = di(2-ethylhexyl) phthalate, DBP = di-butyl phthalate, DINP = di-isononyl phthalate, BPA = bisphenol A
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Androgens, the main male sex steroids, are the critical factors responsible for the development of the male phenotype during embryogenesis and for the achievement of sexual maturation and puberty. In adulthood, androgens remain essential for the maintenance of male reproductive function and behavior. Androgens, acting through the androgen receptor...
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Microcystin-leucine arginine (MC-LR) causes serum testosterone declines and male reproductive disorders. However, the molecular mechanisms underlying the pathological changes are still unclear. In the present study, we aimed to investigate the toxic effects of MC-LR on gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus. Our results d...
Citations
... Studies in pregnant animals with single exposure or binary mixtures of 7 and 10 ED with anti-androgenic action in microdoses confirmed that exposure to a single chemical did not induce or induce rare malformations, while mixtures caused malformations in around 50 % of males. 12 Children, pregnant women, and workers in specific activities constitute the most vulnerable group to exposure to ED. There is growing evidence that exposure to ED during critical periods of embryological development can cause permanent changes in gene expression, a concept similar to that proposed by David Barker about intrauterine growth restriction influencing the prevalence of metabolic syndrome in adult life. ...
... Some reports from studies carried out in the USA, Germany and Canada show that more than 90 % of the individuals evaluated had measurable amounts of BPA in their urine. 12 Exposure to BPA has been associated with an increase in cases of cryptorchidism, hypospadias, and reduced semen quality in men, suggesting a possible interference with male reproductive function. 12 ...
... 12 Exposure to BPA has been associated with an increase in cases of cryptorchidism, hypospadias, and reduced semen quality in men, suggesting a possible interference with male reproductive function. 12 ...
Objectives:
Narrative review evaluating food contamination by endocrine disruptors present in food packaging.
Data source:
The terms "endocrine disruptors" and "food packaging" were used in combination in the PubMed, MEDLINE and SciELO databases, evaluating studies, in humans, published in Portuguese, English, French and Spanish between 1990 and 2023.
Data synthesis:
Packaging, especially those made from plastic or recycled material, is an important source of food contamination by endocrine disruptors. Bisphenols and phthalates are the endocrine disruptors most frequently associated with food contamination from packaging. However, many unknown substances and even those legally authorized can cause harm to health when exposure is prolonged or when substances with additive effects are mixed. Furthermore, the discarding of packaging can cause contamination to continue into the environment.
Conclusion:
Although packaging materials are essential for the transport and storage of food, many of them are associated with chemical contamination. As it is not possible to exclude them from our routine, it is important to develop research aimed at identifying the endocrine disruptors present in them, including the effects of chronic exposure; and that regulatory agencies and industry come together to reduce or prevent this risk. Additionally, consumers must be instructed on how to purchase products, handle them and prepare them to reduce the migration of chemical substances into food.
... At environmentally relevant concentrations (1 nM), this agent is capable of activating the expression of prostate-specific antigen PSA, and inducing accelerated tumor growth in vivo, consequently facilitating the biochemical recurrence in tumors after therapy [42][43][44]. BPA proved to possess androgenic and antiandrogenic effects in rodent models [45]. The molecular mechanisms behind this activity remained unclear. ...
Bisphenol A (BPA) is a ubiquitous synthetic compound used as a monomer in the production of polycarbonate plastics and epoxy resins. Even at low doses, BPA has been associated with the molecular progression of diseases such as obesity, metabolic syndrome, and hormone-regulated cancers due to its activity as an endocrine-disrupting chemical (EDC). Consequently, the use of BPA has been regulated worldwide by different health agencies. BPA structural analogs such as bisphenol S and bisphenol F (BPS and BPF) have emerged as industrial alternatives, but their biological activity in the molecular progression of cancer remains unclear. Prostate cancer (PCa) is a hormone-dependent cancer, and the role of BPA structural analogs in PCa progression is still undescribed. In this work, we use an in vitro model to characterize the transcriptomic effect of low-concentration exposure to bisphenol A, S, or F in the two main stages of the disease: androgen dependency (LNCaP) and resistance (PC-3). Our findings demonstrated that the low concentration exposure to each bisphenol induced a differential effect over PCa cell lines, which marks the relevance of studying the effect of EDC compounds through all the stages of the disease.
... The endocrine role in animals and human are changed by numerous chemicals which are present in the environment and vulnerability to such endocrine-disrupting chemicals EDCs might cause harmful outcomes on the neurological role, fetal/child growth, metabolism, and reproduction. The human species or its offspring badly affected by ETs (Marcoccia et al., 2017). These ETs could be present in numerous products and goods, such as, in deodorant, cosmetic products foodstuff, drinking water, synthetic materials, shampoos, clothes, kinds of toothpaste, body soaps, soil fertilizers, paper, textiles, carpets, utensils, bedding, toys, etc. (Joensen et al., 2009). ...
Environmental Endocrine Toxicants: Biology, Effects, and Management presents important knowledge of human exposure to endocrine toxicants and the related harmful effects. The book highlights the cutting-edge research currently being conducted on the subject and focuses on the challenges of dealing with increasing pollution levels, increased use of synthetic chemicals, and environmental endocrine disruptors that endanger the human endocrine system and its respective hormones.
Found in various man-made and natural substances and materials, endocrine toxicants include pesticides, herbicides, industrial chemicals, solvents and by-products, phytoestrogens, nanomaterials, and chemicals used in personal care products. These endocrine disruptors may mimic or interfere with the body’s hormones and are linked with developmental, reproductive, brain, immune, and other problems.
The volume discusses the many potential endocrine toxicants and the pathways through which they disrupt the endocrine system.
Key features:
Provides an overview of the chemical nature and mechanisms of endocrine disruptors
Discusses the sources of endocrine toxicants
Assesses the impact of endocrine toxicants on a sustainable environment
Looks at endocrine toxicants and their effect on human health, such as on thyroid glands, on human reproduction, etc.
... By impairing the activity of type I and type II 5-α-reductases, some agri-food byproducts affect the testosterone synthesis and prevent the synthesis of the more potent ligand, dihydrotestosterone (DHT) [139]. It has been, hence proposed the combo use of these compounds with standard ADT to improve the efficacy of treatment and delay the onset of CRPC. ...
The globalization and the changes in consumer lifestyles are forcing us to face a deep transformation in food demand and in the organization of the entire food production system. In this new era, the food-loss and food-waste security nexus is relevant in the global debate and avoiding unsustainable waste in agri-food systems as well as the supply chain is a big challenge. “Food waste” is useful for the recovery of its valuable components, thus it can assume the connotation of a “food by-product”. Sustainable utilization of agri-food waste by-products provides a great opportunity. Increasing evidence shows that agri-food by-products are a source of different bioactive molecules that lower the inflammatory state and, hence, the aggressiveness of several proliferative diseases. This review aims to summarize the effects of agri-food by-products derivatives, already recognized as promising therapeutics in human diseases, including different cancer types, such as breast, prostate, and colorectal cancer. Here, we examine products modulating or interfering in the signaling mediated by the epidermal growth factor receptor.
... A number of reports have recognized the interaction of phytoestrogen with androgen receptors, thus exhibiting antiandrogenic activities. 53 Pesticides that are generally used for the management of agricultural and indoor pests are widely suspected as endocrine disruptors. Dichloro-diphenyl trichloroethane and hexachlorocyclohexane pesticides were extensively used pesticides in India until late 1990. ...
The recent reports on milk consumption and its associated risk with hormone related disorders necessitates the evaluation of dairy products for the presence of endocrine disrupting chemicals (EDCs) and ensure the safety of consumers. In view of this, we investigated the possible presence of (anti)androgenic contaminants in raw and commercialized milk samples. For this purpose, a novel HepARE-Luc cell line that stably expresses human androgen receptor (AR) and the androgen responsive luciferase reporter gene was generated and used in the present study. Treatment of this cell line with androgens and corresponding antiandrogen (flutamide) stimulated or inhibited expression of reporter luciferase, respectively. Real time polymerase chain reaction and immunostaining results exhibited transcription response and translocation of AR from the cytoplasm to the nucleus in response to androgen. Observations implied that a cell-based xenobiotic screening assay via AR response can be conducted for assessing the (anti)androgenic ligands present in food chain including milk. Therefore, the cell line was further used to screen the (anti)androgenic activity of a total of 40 milk fat samples procured as raw or commercial milk. Some of the raw and commercial milk fat samples distinctly showed antiandrogenic activities. Subsequently, some commonly used environmental chemicals were also evaluated for their (anti)androgenic activities. Initial observations with molecular docking studies of experimental compounds were performed to assess their interaction with AR ligand binding domain. Furthermore, (anti)androgenic activities of these compounds were confirmed by performing luciferase assay using the HepARE-Luc cell line. None of the test compounds showed androgenic activities rather some of them like Bisphenol A (BPA) and rifamycin showed antiandrogenic activities. In conclusion, our results provide a valuable information about the assessment of (anti)androgenic activities present in milk samples. Overall, it is proposed that a robust cell-based CALUX assay can be used to assess the (anti)androgenic activities present in milk which can be attributed to different environmental chemicals present therein.
... However, when finasteride is added, it prevents the conversion of T to dihydrotestosterone (DHT). DHT has a 10-fold higher potency than T for inducing iAR functions [13]. This means that since LNCaP 104-R2 has 10 times more iAR than normal, when iAR functions are decreased 10-fold by eliminating DHT, the end result is the equivalent of a normal amount of iAR with a normal amount of DHT, which is why the cancer can now grow at its maximal rate. ...
It has been shown that when the amount of intracellular androgen receptor in prostate cancer is greatly amplified, such as in the cell line LNCaP 104-R2, then testosterone will stop the growth of those cancer cells. This is the principle behind bipolar androgen therapy, which alternates amplifying intracellular androgen receptors by using very low levels of testosterone with supraphysiologic levels of testosterone. This approach has achieved some limited success in human patients. However, as these cycles continue, some mutations are expected to arise that give the cancer cells a selective growth advantage and lessen the effectiveness of bipolar androgen therapy.
... Moreover, naringenin has been found to act as antidiabetic agent through up-regulation of adenosine monophosphateactivated protein kinase (AMPK), and inhibition of gluconeogenesis. In addition, it also showed antimicrobial, hepatoprotective, neuroprotective, cardioprotective and nephroprotective activity, cell damage prevention and antioxidant effects, by modulating reactive oxygen species (ROS) levels and increasing superoxide dismutase (SOD) in malignancies, chronic and metabolic diseases [10,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Moreover, naringenin shows immunomodulatory and anti-inflammatory effects by reducing cytokine production in macrophages and dendritic cells, antigen cross-presentation in dendritic cells improvement, lysosomedependent cytokine degradation induction, inhibition of transforming growth factor-β (TGF-β), suppression of regulatory T-cells (Tregs), and down-regulation of interleukin-1β (IL-1β), which are all mechanisms playing a significant role in various inflammatory airway conditions such as chronic obstructive pulmonary disease and even SARS-CoV-2 infections [12,25,[29][30][31][32][33][34][35]. ...
Naringenin is an important phytochemical which belongs to the flavanone group of polyphenols, and is found mainly in citrus fruits like grapefruits and others such as tomatoes and cherries plus medicinal plants derived food. Available evidence demonstrates that naringenin, as herbal medicine, has important pharmacological properties, including anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. Collected data from in vitro and in vivo studies shows the inactivation of carcinogens after treatment with pure naringenin, naringenin-loaded nanoparticles, and also naringenin in combination with anticancer agents in various malignancies, such as colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancer, bladder neoplasms, gastric cancer, and osteosarcoma. Naringenin inhibits cancer progression through multiple mechanisms, like apoptosis induction, cell cycle arrest, angiogenesis hindrance, and modification of various signaling pathways including Wnt/ß-catenin, PI3K/Akt, NF-ĸB, and TGF-β pathways. In this review, we demonstrate that naringenin is a natural product with potential for the treatment of different types of cancer, whether it is used alone, in combination with other agents, or in the form of the naringenin-loaded nanocarrier, after proper technological encapsulation.
... In adulthood, ERα is normally found primarily in stromal cells and ERβ in differentiated epithelium [15][16][17]. It is noteworthy that the prostate gland is particularly sensitive to estrogen exposure during its critical developmental period, due to adult estrogenic responses [15,18]. ...
... These also include endocrine disruptors (EDs), defined as exogenous substances or a mixture that "alters function(s) of the endocrine system, causing adverse health effects in an intact organism, or its progeny, or in a (sub)populations" [21]. EDs can act at a low dose and are found in many daily products, such as beverage and plastic bottles, food cans and overall food packaging, epoxy plasticbased electronics, recycled paper, and so on [18,22]. The main exposure to these contaminants occurs through the intake of contaminated water and food, but can also be taken through other sources, such as direct dermal contact or inhalation of polluted air [22,23]. ...
... This is especially true for androgens [28]. The major naturally occurring steroids with androgenic activity are (in decreasing order of relative potency): 5α-dihydrotestosterone (DHT, 150-200 %), testosterone (T, 100 %), 3α-androstanediol (3α-diol, 65 %), androst-4-ene3,17-dione (AD, 25 %), androsterone (AND, 10%), and dehydroepiandrosterone (DHEA, 10%) [18] (Figure 1). About 95 % of T is produced and secreted by Leydig cells in the testis, and the remaining 5 % is produced in adrenal glands by conversion of precursors (e.g., DHEA, DHEA sulfate, and androstenedione) [18]. ...
The role of endocrine disruptors (EDs) in the human prostate gland is an overlooked issue even though the prostate is essential for male fertility. From experimental models, it is known that EDs can influence several molecular mechanisms involved in prostate homeostasis and diseases, including prostate cancer (PCa), one of the most common cancers in the male, whose onset and progression is characterized by the deregulation of several cellular pathways including androgen receptor (AR) signaling. The prostate gland essentiality relies on its function to produce and secrete the prostatic fluid, a component of the seminal fluid, needed to keep alive and functional sperms upon ejaculation. In physiological condition, in the prostate epithelium the more-active androgen, the 5α-dihydrotestosterone (DHT), formed from testosterone (T) by the 5α-reductase enzyme (SRD5A), binds to AR and, upon homodimerization and nuclear translocation, recognizes the promoter of target genes modulating them. In pathological conditions, AR mutations and/or less specific AR binding by ligands modulate differently targeted genes leading to an altered regulation of cell proliferation and triggering PCa onset and development. EDs acting on the AR-dependent sig-naling within the prostate gland can contribute to the PCa onset and to exacerbating its development .
... In an in vitro study, treatment of human testis explants of reproductively mature men with DEHP or MEHP led to an impaired testosterone secretion, most likely by inhibiting the production of testosterone precursor steroids (Desdoits-Lethimonier et al., 2012). In rats, phthalates were reported to have antiandrogenic activity, resulting in lesser testosterone concentrations and abnormalities in the reproductive tract (Foster et al., 2001;Johnson et al., 2012;Marcoccia et al., 2017) indicating there was an indirect aberrant effect on steroidogenesis. ...
The decreasing trend in human and domestic animal fertility in recent decades has resulted in the question of whether reduced sperm quality is associated with changes in global climate and the environment. Proposed causes for reduced sperm quality include environmental contaminants, which enter into the body of animals through the food chain and are transported to the reproductive tract, where contaminating agents can have effects on fertilization capacities of gametes. In this review, there is a focus on various environmental contaminants and potential effects on male fertility. Human-derived contaminants, particularly endocrine-disrupting phthalates and the pesticide atrazine, are discussed. Naturally occurring toxins are also addressed, in particular mycotoxins such as aflatoxin which can be components in food consumed by humans and animals. Mechanisms by which environmental contaminants reduce male fertility are not clearly defined; however, are apparently multifactorial (i.e., direct and indirect effects) with there being diverse modes of action. Results from studies with humans, rodents and domestic animals indicate there are deleterious effects of contaminants on male gametes at various stages of spermatogenesis (i.e., in the testis) during passage through the epididymis, and in mature spermatozoa, after ejaculation and during capacitation. Considering there is never detection of a single contaminant, this review addresses synergistic or additive effects of combinations of contaminants. There is new evidence highlighted for the long-lasting effects of environmental contaminants on spermatozoa and developing embryos. Understanding the risk associated with environmental contaminants for animal reproduction may lead to new management strategies, thereby improving reproductive processes.
... Lastly, it is important to note that such phytochemicals are in of themselves EDCs (Marcoccia et al. 2017). One example is the soy phytochemical, genistein, which is a well characterized estrogen receptor agonist. ...
The effects of Endocrine Disrupting Chemicals (EDCs) on the current obesity epidemic is a growing field of interest. Numerous EDCs have shown the potential to alter energy metabolism, which may increase the risk of obesity, in part, through direct actions on adipose tissue. While white adipose tissue has historically been the primary focus of this work, evidence of the EDC-induced disruption of brown and beige adipose tissues continues to build. Both brown and beige fat are thermogenic adipose depots rich in mitochondria that dispense heat when activated. Due to these properties, brown and beige fat are implicated in metabolic diseases such as obesity, diabetes, and cachexia. This review delves into the current literature of different EDCs, including bisphenols, dioxins, air pollutants, phthalates, and phytochemicals. The possible implications that these EDCs have on thermogenic adipose tissues are covered. This review also introduces the possibility of using brown and beige fat as a therapeutic target organ by taking advantage of some of the properties of EDCs. Collectively, we provide a comprehensive discussion of the evidence of EDC disruption in white, brown, and beige fat and highlight gaps worthy of further exploration.
