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Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) that is widely used in the manufacturing of plastics and inner linings of food cans. Previously, it was reported that BPA disturbed the sexual dimorphic nucleus of the hypothalamus and delaying the onset of puberty attributed to an estrogenic action. In addition, BPA during the perinatal period increased LH serum concentrations in male offspring of dams at doses below the reproductive NOAEL (No Observable Adverse Effect Level) based upon World Health Organization guidelines. Based upon these findings, the objective of this study was to (1) determine the effects of perinatal treatment with low doses of BPA on regulation of spermatogenesis in adult offspring and (2) elucidate molecular mechanisms involved in the pathogenesis of gonadal dysfunction. The expression of genes related to spermatogenesis was disrupted with adverse consequences on sperm production, reserves, and function. Both BPA treated groups exhibited reduction in sperm production and epithelial height of seminiferous tubules, accompanied by diminished integrity of the acrosome and plasma membrane, decreased mitochondrial activity and increased incidence of morphological abnormalities. The sperm transit time was also slower. However, only in the group receiving the higher BPA dose was transcript expression of genes affected (reduced Ar and increased Esr1). It is of interest that serum testosterone levels were elevated in the same group where Ar was decreased. Data suggest that exposure to low BPA doses during hypothalamic sexual differentiation period produces permanent deleterious effects on spermatogenesis in adulthood. [ABSTRACT FROM AUTHOR]

Abstract Di (2-ethylhexyl) phthalate or DEHP is classified as an endocrine-disrupting chemical. It is used as a plasticizer and pesticide additive. Moreover, it has a half-life of about 150–300 days. Thus, it is present in the soil environment and soil risk assessments for DEHP are needed. However, a number of studies have focused on the effects of DEHP in a single soil species. In this study, we conducted acute and chronic toxicity testing for DEHP using varied soil species, including plants, earthworms, soil algae, Collembola, and soil nematodes. In the plant toxicity test, no effect was observed at very high concentration except at some endpoints, and no effect was observed in the earthworm toxicity test. However, there were adverse effects on soil algae, Collembola, and nematodes. Notably, in the Collembola assays, the survival of adults decreased significantly at very high concentrations, whereas reproduction was hindered at low concentrations. Similar inhibition of reproduction was noted in the soil nematode assay. This suggests that DEHP has a greater influence on fertility than survival in the adult test species. However, besides hindered reproduction, no effect was observed on soil species at environmentally relevant concentrations. Graphical abstract Image Highlights • We observed acute and chronic toxicity of DEHP on eight soil species. • In acute assay, low toxicity was noted even at the high concentrations. • Chronic effects were observed albeit at unrealistic environmental concentrations. • Especially, reproductive effects were noted for collembola and soil nematodes. • Reproductive effects persisted even at DEHP concentrations of 10 mg/kg. [ABSTRACT FROM AUTHOR]

Phthalates are chemicals ubiquitously used in industry. Individual phthalates have been found to adversely affect female reproduction; however, humans are exposed to a mixture of phthalates daily, primarily through ingestion. Previous studies show that exposure to an environmentally relevant mixture of phthalates (Mix) can affect female reproduction. Little research, however, has been conducted on the effects of short-term (1 month) and long-term (6 months) exposure to Mix on ovarian functions. Thus, this study tested the hypothesis that short-term and long-term exposure to Mix alters ovarian folliculogenesis, serum hormone concentrations, pituitary gene expression, and ovarian expression of genes involved in steroidogenesis, apoptosis, cell cycle regulation, and oxidative stress. Adult CD-1 female mice were exposed to vehicle control (corn oil) or Mix (0.15–1500 ppm) in the chow for 1 or 6 months. Exposure to Mix for 1 month increased the number of atretic follicles (0.15 ppm), altered ovarian gene expression (0.15 ppm, 1500 ppm), and decreased serum testosterone (1.5 ppm) compared to control. Exposure to Mix for 6 months increased serum follicle-stimulating hormone (FSH) (0.15 ppm), decreased serum luteinizing hormone (LH) (0.15 ppm, 1.5 ppm, and 1500 ppm), decreased serum estradiol (1500 ppm), altered pituitary gene expression (1500 ppm), increased the number (1500 ppm) and percentage (1.5 ppm and 1500 ppm) of primordial follicles, and decreased the percentage of preantral (1500 ppm) and antral (1.5 ppm and 1500 ppm) follicles compared to control. These data indicate that exposure to Mix can alter folliculogenesis, steroidogenesis, and gene expression in female mice. • Phthalate mixture (1 month) altered ovarian gene expression. • Phthalate mixture (1 month) decreased serum testosterone. • Phthalate mixture (6 months) increased FSH and decreased LH and estradiol. • Phthalate mixture (6 months) altered pituitary gene expression. • Phthalate mixture (6 months) altered folliculogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Indomethacin (NSAID) is an endocrine-disrupting chemical (EDC) that has been demonstrated to induce alterations in reproductive organs while Black Tea Extract (BTE), an antioxidant, is capable of protecting against EDC-induced alterations. Aims & Objectives: The current study was designed to investigate the role of black tea extract on biochemical, hormonal, and histological changes in the prostate of male Wister rats treated with indomethacin drugs. Materials and Methods: Adult rats were divided into four groups (n = 6/group); Group I (control); Group II (indomethacin, 5 mg/kg b.wt.; i.p.); Group III (BTE, 2.5 g tea leaf/dL of water, i.e., 2.5% of aqueous BTE, orally) and Group IV (indomethacin + BTE) for 21 successive days. Sperm Count, Motility, Prostate-Specific Antigen (PSA), Testosterone levels, total protein, GSH, CAT, and MDA levels and the histopathological aspects of the prostate gland were studied. Statistical Analysis: Statistical comparisons were performed using the one-way ANOVA, followed by post-hoc t-test. Results: Indomethacin treated rats “Group” II exhibited a significant (P≤0.05) declining in the sperm count, motility PSA and testosterone concentration, total protein, GSH concentration, and CAT activity. A high concentration of MDA levels in the serum indicated the appearance of oxidative stress status in the Wister rats. The indomethacin had a significant impact on the weight, and histopathology of glandular “acini” and excretory “ducts” revealed hyperplasia, intra-luminal budding of epithelia as well as tubular atrophy. Conclusion: Administration of black tea extract abrogated the toxic effect induced by indomethacin on the prostate gland.

Highlights • EDCs tested have a negative impact on human sperm functions. • There are no significant differences in the viability of euploidy and aneuploidy spermatozoa following exposure to EDCs. • TCDD, DBCP, and Diaz adversely affect the viability of Y spermatozoa more than X spermatozoa. • A reduction in Y sperm viability may result in a female-biased sex ratio of offspring at birth. Abstract Although equal numbers of X and Y spermatozoa are produced during spermatogenesis, the sex chromosome ratio in ejaculated spermatozoa can be altered by exposure to endocrine-disrupting chemicals (EDCs), which can be reflected by altered sex ratios at birth. Here, we hypothesized EDCs affect sperm functions and viability of X and Y chromosome-bearing human spermatozoa. After exposure to genistein (Gen), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dibromochloropropane (DBCP), and diazinon (Diaz), we evaluated motility, viability, capacitation, and differential viability of X and Y spermatozoa. All EDCs tested altered sperm viability, motility, and capacitation. Interestingly, the Y/X ratio of live spermatozoa was significantly lower in sperm treated with TCDD, DBCP, and Diaz than control spermatozoa. Our results suggest that some of EDCs have larger effects on the viability of Y spermatozoa than X spermatozoa, implicating that a reduction in Y sperm viability may result in a female-biased sex ratio of offspring at birth. [ABSTRACT FROM AUTHOR]

Abstract We investigated the effects of activated carbon, used as constructed wetlands (CWs) medium, on its ability to remove four emerging endocrine-disrupting chemicals (EDCs): bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS) and 4- tert -butylphenol (4- tert -BP). Two types of CWs planted with common reed were constructed, one with pumice rock called normal CW and the other was amended with activated carbon (AC) called AC-CW. EDCs contaminated synthetic wastewater (5 mg/L of each) was treated by CWs for 8 weeks. AC-CW completely and sustainably removed all four EDCs (98–100%) starting immediately and continuing throughout the experiment. Removal performances of all EDCs by AC-CW were significantly higher than those by normal CW. After experiment, no BPA and BPF and very small amounts of BPS and 4- tert -BP were detected in AC. In AC-CW, final elimination step of EDCs might be biodegradation. In addition, bacterial populations on AC component of AC-CW were one–two orders higher than those on the pumice rock of normal CW. Therefore, in AC-CW, EDCs were initially adsorbed onto AC, where they could be effectively degraded by high bacterial population. Graphical abstract Image 1 Highlights • Activated carbon-amended constructed wetlands (AC-CWs) were constructed. • AC-CWs treated four EDCs (BPA, BPF, BPS and 4- tert -BP) contaminated wastewater. • AC-CWs showed efficient and sustainable removal of four EDCs from wastewater. • Bacterial population on AC in AC-CWs were higher than on pumice rock in normal CWs. • EDCs were initially adsorbed then degraded by attached-bacteria. [ABSTRACT FROM AUTHOR]

Thousands of safety-related studies have been published on bisphenol A (BPA), an ubiquitous environmental pollutant with estrogenic activity and many other potential biological effects. In recent years, BPA exposure has been shown to cause anovulation and infertility through irreversible alteration of the hypothalamic-pituitary-gonadal axis in several organisms, including fish and mammals. Recently, the European Chemical Agency classified BPA as a “substance of very high concern” because of its endocrine-disrupting properties, which have serious effects on human health. Given the risk of exposure to BPA as a pollutant in the environment, food, and drinking water, the objective of our study was to assess the effects of this compound on the adeno-hypophysis by means of a histopathological and morphometric study of the gonadotroph cells. In addition, using quantitative real-time PCR (qRT-PCR) assays, we analyzed the changes in the expression of Cyp19b (an aromatase gene). Zebrafish were randomly distributed into five groups: a control group and 4 treated groups which were exposed to different BPA concentrations (1, 10, 100 and 1000 µg/L). The effects of the different doses on Cyp19b mRNA molecules followed a non-monotonic curve, with the 1 and 1000 µg/L doses causing dramatic decreases in the number of Cyp19b transcripts while the doses of 10 and 100 µg/L caused important increases. The consequences might be deregulation of gonadotropic hormones causing degeneration of gonadotropic cells, as observed in BPA treated animals. This is the first study in which the gonadotroph cells have been evaluated using histomorphological endpoints after BPA exposure in zebrafish. [ABSTRACT FROM AUTHOR]

Guppies (Poecilia reticulata) are considered a candidate model species for the identification and testing of endocrine-disrupting chemicals. Male guppies may be used to address the challenge of making potential linkages between alterations of biomarkers, both at the cellular and organ level, and adverse outcomes. In the present study, a predictive relationship between sex characteristics and reproductive output was observed in male guppies that underwent a long-term toxicity test with 0.5 μg/L 17β-estradiol administered during the juvenile period. Radioimmunoassay and western blot analyses demonstrated that 17β-estradiol exposure caused a significant increase in testicular 17β-estradiol levels as well as the induction of exposure biomarkers, namely hepatic vitellogenin. Exposure to 17β-estradiol also caused a significant decrease in testosterone levels, which consequently reduced the gonadosomatic index, sperm counts, and the coloration index. These changes of male sexual characteristics further translated into adverse influences on reproduction, as measured by a decrease in offspring production and survival rate. Our results suggest that the above-mentioned sexual characteristics of male guppies may be considered potential in vivo biomarkers of estrogen effects on reproduction. [ABSTRACT FROM AUTHOR]

The environmental impact of endocrine-disrupting chemicals (EDCs)—compounds that interfere with endocrine system function at minute concentrations—is now well established. In recent years, concern has been mounting over a group of endocrine disruptors known as hormonal growth promotants (HGPs), which are natural and synthetic chemicals used to promote growth in livestock by targeting the endocrine system. One of the most potent compounds to enter the environment as a result of HGP use is 17β-trenbolone, which has repeatedly been detected in aquatic habitats. Although recent research has revealed that 17β-trenbolone can interfere with mechanisms of sexual selection, its potential to impact sequential female mate choice remains unknown, as is true for all EDCs. To address this, we exposed female guppies ( Poecilia reticulata ) to 17β-trenbolone at an environmentally relevant level (average measured concentration: 2 ng/L) for 21 days using a flow-through system. We then compared the response of unexposed and exposed females to sequentially presented stimulus (i.e., unexposed) males that varied in their relative body area of orange pigmentation, as female guppies have a known preference for orange colouration in males. We found that, regardless of male orange pigmentation, both unexposed and exposed females associated with males indiscriminately during their first male encounter. However, during the second male presentation, unexposed females significantly reduced the amount of time they spent associating with low-orange males if they had previously encountered a high-orange male. Conversely, 17β-trenbolone-exposed females associated with males indiscriminately (i.e., regardless of orange colouration) during both their first and second male encounter, and, overall, associated with males significantly less than did unexposed females during both presentations. This is the first study to demonstrate altered sequential female mate choice resulting from exposure to an endocrine disruptor, highlighting the need for a greater understanding of how EDCs may impact complex mechanisms of sexual selection. [ABSTRACT FROM AUTHOR]

Abstract: Exposure to endocrine‐disrupting chemicals may adversely affect animals, particularly during development. Tris(1,3‐dichloroisopropyl) phosphate (TDCIPP) is an organophosphate with anti‐androgen function in vitro that is present in indoor dust at relatively high concentrations. In male rats, androgens are necessary for the development of reproductive organs, as well as the endocrine and central nervous systems. However, we currently do not know the exact effects of TDCIPP exposure through suckling on subsequent reproductive behavior in males. Here, we show that TDCIPP exposure (25–250 mg kg–1 via oral administration over 28 consecutive days post‐birth) suppressed male sexual behavior and reduced testes size. These changes were dose‐dependent and appeared first in adults rather than in juveniles. These results demonstrate that TDCIPP exposure led to normal body growth and appearance in juveniles, but disrupted the endocrine system and physiology in adults. Therefore, assays should be performed using adult animals to ensure accuracy, and to confirm the influence of chemical substances given during early mammalian life. [ABSTRACT FROM AUTHOR]

This study describes the determination of the species sensitivity distribution (SSD)-based soil hazardous contamination of bisphenol A for environmental risk assessment. We conducted a battery of bioassays, including acute assays using eight species from six different taxonomic groups and chronic assays using five species from four different taxonomic groups. We determined that our dataset satisfied Australia & New Zealand’s guidelines for applying the SSD methodology. Finally, the chronic soil HC 5 and HC 50 values for bisphenol A were estimated to be 13.7 and 74.7 mg/kg soil, respectively, for soil ecosystem protection against chronic exposure using the data generated from this and previous studies. Because the soil standard values of bisphenol A for protection of the soil ecosystem are not currently available, the HC values of bisphenol A that we suggested based on the SSD approach would be applied as fundamental data to establish soil standards of bisphenol A for soil ecosystem protection. To our knowledge, this is the first study reporting the soil hazardous concentration of bisphenol A for environmental risk assessment. [ABSTRACT FROM AUTHOR]

Abstract: Adverse outcome pathways (AOPs) are a novel concept that effectively considers the toxic modes of action and guides the ecological risk assessment of chemicals. To better use toxicity data including biochemical or molecular responses and mechanistic data, we further developed a species sensitivity–weighted distribution (SSWD) method for bisphenol A and 4‐nonylphenol. Their aquatic predicted‐no‐effect concentrations (PNECs) were derived using the log‐normal statistical extrapolation method. We calculated aquatic PNECs of bisphenol A and 4‐nonylphenol with values of 4.01 and 0.721 µg/L, respectively. The ecological risk of each chemical in different aquatic environments near Tianjin, China, a coastal municipality along the Bohai Sea, was characterized by hazard quotient and probabilistic risk quotient assessment techniques. Hazard quotients of 7.02 and 5.99 at 2 municipal sewage sites using all of the endpoints were observed for 4‐nonylphenol, which indicated high ecological risks posed by 4‐nonylphenol to aquatic organisms, especially endocrine‐disrupting effects. Moreover, a high ecological risk of 4‐nonylphenol was indicated based on the probabilistic risk quotient method. The present results show that combining the SSWD method and the AOP concept could better protect aquatic organisms from adverse effects such as endocrine disruption and could decrease uncertainty in ecological risk assessment. Environ Toxicol Chem 2018;37:551–562. © 2017 SETAC [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that many environmental chemicals can cross the human placental barrier. However, the risk regarding gestational exposure of emerging endocrine-disrupting chemicals (EDCs) is unclear. In this study, the occurrence of 24 EDCs, such as bisphenol A analogs, parabens, triclocarban, and triclosan, was investigated in serum and urine samples from Chinese pregnant women. Some metabolites were determined in matched serum–urine pairs (n = 75) to perform a comprehensive assessment of exposure. The placental transfer efficiency (PTE) of the detected chemicals was determined in matched maternal–cord serum pairs (n = 110). The mean PTEs of the chemicals showed a large variation from 43.1% to 171.0%. The potential effects of physicochemical properties, molecular structures, and biological factors on PTE were investigated using multiple linear regression models and molecular docking. We found that the PTE of methyl paraben, ethyl paraben, and propyl paraben was associated with their increasing alkyl chain lengths. Furthermore, a comprehensive exposure assessment of EDCs showed that 62.7% of pregnant women had a health index > 1, which indicted potential health risks during pregnancy. However, toxicity and the underlying mechanisms of these EDCs remain to be further studied. [Display omitted] • Twenty-four endocrine-disrupting chemicals (EDCs) were detected in pregnant women. • The placental transfer efficiency (PTE) of EDCs was measured. • The effects of physicochemical and biological factors on PTEs were investigated. • Potential health risks of target EDCs to pregnant women were proposed. [ABSTRACT FROM AUTHOR]

The growing global deterioration in several aspects of human health has been partly attributed to hazardous effects of endocrine-disrupting chemicals (EDCs) exposure. Therefore, experts and government regulatory agencies have consistently advocated for studies on the combined effects of EDCs that model human exposure to multiple environmental chemicals in real life. Here, we investigated how low concentrations of bisphenol A (BPA), and phthalates compounds affect the Sertoli cell glucose uptake/lactate production in the testis and male fertility. An EDC mixture containing a detected amount of each chemical compound in humans, called daily exposure (DE), and DE increased in magnitude by 25 (DE25), 250 (DE250), and 2500 (DE2500), and corn oil (control) were administered for six weeks to male mice. We found that DE activated estrogen receptor beta (Erβ) and glucose-regulated protein 78 (Grp 78) and disrupted the estradiol (E2) balance. In addition, DE25, DE250, and DE2500 doses of the EDC mixture via binding with Sertoli cells' estrogen receptors (ERs) inhibited the glucose uptake and lactate production processes by downregulating glucose transporters (GLUTs) and glycolytic enzymes. As a result, endoplasmic reticulum stress (ERS), marked by unfolded protein response (UPR) activation, was induced. The accompanying upregulation of activating transcription factor 4 (ATF4), inositol requiring enzyme-1 (IRE1), C/EBP homologous protein (CHOP), and mitogen-activated protein kinase (MAPK) signaling promoted antioxidant depletion, testicular cell apoptosis, abnormal regulation of the blood−testis barrier, and decreased sperm count. Therefore, these findings suggest that human and wildlife exposure to multiple environmental chemicals can produce a wide range of reproductive health complications in male mammals. [Display omitted] • Endocrine-disrupting chemicals (EDCs) mixture inhibits testicular glucose uptake. • Nutrient deprivation in testicular cells induced endoplasmic reticulum stress (ERS). • Persistent unfolded protein response promoted MAPK signaling-dependent apoptosis. • Abnormal regulation of blood−testis barrier is ERS- and MAPK signaling-dependent. • Exposure to human-relevant EDCs mixture doses affected male reproductive health in mice. [ABSTRACT FROM AUTHOR]

Despite a growing literature highlighting the potential impact of human-induced environmental change on mechanisms of sexual selection, relatively little is known about the effects of chemical pollutants on male-male competition. One class of environmental pollutant likely to impact male competitive interactions is the endocrine-disrupting chemicals (EDCs), a large and heterogeneous group of chemical contaminants with the potential to influence morphology, physiology and behaviour at minute concentrations. One EDC of increasing concern is the synthetic, androgenic steroid 17β-trenbolone, which is used globally to promote growth in beef cattle. Although 17β-trenbolone has been found to cause severe morphological and behavioural abnormalities in fish, its potential impact on male-male competition has yet to be investigated. To address this, we exposed wild male guppies ( Poecilia reticulata ) to an environmentally realistic concentration of 17β-trenbolone (average measured concentration: 8 ng/L) for 21 days using a flow-through system. We found that, in the presence of a competitor, 17β-trenbolone-exposed males carried out more frequent aggressive behaviours towards rival males than did unexposed males, as well as performing less courting behaviour and more sneak (i.e., coercive) mating attempts towards females. Considering that, by influencing mating outcomes, male-male competition has important consequences for population dynamics and broader evolutionary processes, this study highlights the need for greater understanding of the potential impact of EDCs on the mechanisms of sexual selection. [ABSTRACT FROM AUTHOR]

Study Question: Is diethylstilbestrol (DES), a prototypical endocrine-disrupting chemical (EDC), able to induce physiological changes in human spermatozoa and affect progesterone actions?Summary Answer: DES promoted Ca2+ flux into human spermatozoa by activating the cation channel of sperm (CatSper) and suppressed progesterone-induced Ca2+ signaling, tyrosine phosphorylation and sperm functions.What Is Known Already: DES significantly impairs the male reproductive system both in fetal and postnatal exposure. Although various EDCs affect human spermatozoa in a non-genomic manner, the effect of DES on human spermatozoa remains unknown.Study Design, Size, Duration: Sperm samples from normozoospermic donors were exposed in vitro to a range of DES concentrations with or without progesterone at 37°C in a 5% CO2 incubator to mimic the putative exposure to this toxicant in seminal plasma and the female reproductive tract fluids. The incubation time varied according to the experimental protocols. All experiments were repeated at least five times using different individual sperm samples.Participants/materials, Setting, Methods: Human sperm intracellular calcium concentrations ([Ca2+]i) were monitored with a multimode plate reader following sperm loading with Ca2+ indicator Fluo-4 AM, and the whole-cell patch-clamp technique was performed to record CatSper and alkalinization-activated sperm K+ channel (KSper) currents. Sperm viability and motility parameters were assessed by an eosin-nigrosin staining kit and a computer-assisted semen analysis system, respectively. The ability of sperm to penetrate into viscous media was examined by penetration into 1% methylcellulose. The sperm acrosome reaction was measured using chlortetracycline staining. The level of tyrosine phosphorylation was determined by western blot assay.Main Results and the Role Of Chance: DES exposure rapidly increased human sperm [Ca2+]i dose dependently and even at an environmentally relevant concentration (100 pM). The elevation of [Ca2+]i was derived from extracellular Ca2+ influx and mainly mediated by CatSper. Although DES did not affect sperm viability, motility, penetration into viscous media, tyrosine phosphorylation or the acrosome reaction, it suppressed progesterone-stimulated Ca2+ signaling and tyrosine phosphorylation. Consequently, DES (1-100 μM) significantly inhibited progesterone-induced human sperm penetration into viscous media and acrosome reaction.Large Scale Data: N/A.Limitations, Reasons For Caution: Although DES has been shown to disturb progesterone actions on human spermatozoa, this study was performed in vitro, and caution must be taken when extrapolating the results in practical applications.Wider Implications Of the Findings: The present study revealed that DES interfered with progesterone-stimulated Ca2+ signaling and tyrosine phosphorylation, ultimately inhibited progesterone-induced human sperm functions and, thereby, might impair sperm fertility. The non-genomic manner in which DES disturbs progesterone actions may be a potential mechanism for some estrogenic endocrine disruptors to affect human sperm function.Study Funding/competing Interests: National Natural Science Foundation of China (No. 31400996); Natural Science Foundation of Jiangxi, China (No. 20161BAB204167 and No. 20142BAB215050); open project of National Population and Family Planning Key Laboratory of Contraceptives and Devices Research (No. 2016KF07) to T. Luo; National Natural Science Foundation of China (No. 81300539) to L.P. Zheng. The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Increased exposure to manmade chemicals may be linked to an increase in immune-related diseases in humans and immune system dysfunction in wildlife. Phthalates are a group of endocrine-disrupting chemicals (EDCs) suspected to influence the immune system. The aim of this study was to characterize the persistent effects on leukocytes in the blood and spleen, as well as plasma cytokine and growth factor levels, one week after the end of five weeks of oral treatment with dibutyl phthalate (DBP; 10 or 100 mg/kg/d) in adult male mice. Flow cytometry analysis of the blood revealed that DBP exposure decreased the total leukocyte count, classical monocyte and T helper (Th) populations, whereas it increased the non-classical monocyte population compared to the vehicle control (corn oil). Immunofluorescence analysis of the spleen showed increased CD11b + Ly6G + (marker of polymorphonuclear myeloid-derived suppressor cells; PMN-MDSCs), and CD43 + staining (marker of non-classical monocytes), whereas CD3 + (marker of total T cells) and CD4 + (marker of Th cells) staining decreased. To investigate the mechanisms of action, levels of plasma cytokines and chemokines were measured using multiplexed immunoassays and other key factors were analyzed using western blotting. The observed increase in M-CSF levels and the activation of STAT3 may promote PMN-MDSC expansion and activity. Increased ARG1, NOX2 (gp91phox), and protein nitrotyrosine levels, as well as GCN2 and phosphor-eIRFα, suggest that oxidative stress and lymphocyte arrest drive the lymphocyte suppression caused by PMN-MDSCs. The plasma levels of IL-21 (promotes the differentiation of Th cells) and MCP-1 (regulates migration and infiltration of monocytes/macrophages) also decreased. These findings show that adult DBP exposure can cause persistent immunosuppressive effects, which may increase susceptibility to infections, cancers, and immune diseases, and decrease vaccine efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Bisphenol A (BPA) is one of the most widely used synthetic compound in the manufacture of polycarbonate plastics and epoxy resins. Worryingly, BPA is an endocrine disrupting chemical (EDC) with an estrogenic, androgenic, or anti-androgenic activities. However, the vascular implications of BPA exposome in pregnancy is unclear. In this sense, the present work proposed to understand how BPA exposure impair the vasculature of the pregnant women. To elucidate this, ex vivo studies were performed using human umbilical arteries to explore the acute and chronic effects of BPA. The mode of action of BPA was also explored by analysing the activity (by ex vivo studies) and expression (in vitro studies) analysis of Ca 2+ and K + -channels and soluble guanyl cyclase. Moreover, in silico docking simulations were performed to unveil the modes of interactions of BPA with the proteins involved in these signalling pathways. Our study showed that the exposure to BPA may modify the vasorelaxant response of HUA, interfering with NO/sGC/cGMP/PKG pathway by modulation of sGC and activation of BKCa channels. Moreover, our findings suggest that BPA can modulate the HUA reactivity, increasing the L-type Ca 2+ Channels (LTCC) activity, a common vascular response observed in hypertensive disorders of pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to polychlorinated biphenyls (PCBs), a class of endocrine-disrupting chemicals, can result in altered reproductive behavior in adulthood, especially when exposure occurs during critical periods of brain sexual differentiation in the fetus. Whether PCBs alter other sexually dimorphic behaviors such as those involved in anxiety is poorly understood. To address this, pregnant rat dams were injected twice, on gestational days 16 and 18, with the weakly estrogenic PCB mixture Aroclor 1221 (A1221) at one of two low dosages (0.5 mg/kg or 1.0 mg/kg, hereafter 1.0 and 0.5), estradiol benzoate (EB; 50 μg/kg) as a positive estrogenic control, or the vehicle (3% DMSO in sesame oil). We also conducted a comprehensive assessment of developmental milestones of the F1 male and female offspring. There were no effects of treatment on sex ratio at birth and age at eye opening. Puberty, assessed by vaginal opening in females and preputial separation in males, was not affected in females but was advanced in males treated with A1221 (1.0). Males and females treated with A1221 (both dosages) were heavier in early adulthood relative to controls. The earliest manifestation of this effect developed in males prior to puberty and in females slightly later, during puberty. Anxiety-like behaviors were tested using the light:dark box and elevated plus maze tests in adulthood. In females, anxiety behaviors were unaffected by treatment. Males treated with A1221 (1.0) showed reduced indices of anxiety and increased activity in the light:dark box but not the elevated plus maze. EB failed to replicate the phenotype produced by A1221 for any of the developmental and behavioral endpoints. Collectively, these results indicate that PCBs increase body weight in both sexes, but their effects on anxiety-like behaviors are specific to males. Furthermore, differences between the results of A1221 and EB suggest that the PCBs are likely acting through mechanisms distinct from their estrogenic activity. [ABSTRACT FROM AUTHOR]

Background Elevated blood or urinary concentrations of endocrine-disrupting chemicals ( EDCs) may be related to increased risk of type 2 diabetes ( T2D). The aim of the present study was to assess the role of EDCs in affecting risk of T2D and related metabolic traits. Methods MEDLINE was searched for cross-sectional and prospective studies published before 8 March 2014 into the association between EDCs (dioxin, polychlorinated biphenyl [ PCB], chlorinated pesticide, bisphenol A [ BPA], phthalate) and T2D and related metabolic traits. Three investigators independently extracted information on study design, participant characteristics, EDC types and concentrations, and association measures. Results Forty-one cross-sectional and eight prospective studies from ethnically diverse populations were included in the analysis. Serum concentrations of dioxins, PCBs, and chlorinated pesticides were significantly associated with T2D risk; comparing the highest to lowest concentration category, the pooled relative risks ( RR) were 1.91 (95% confidence interval [ CI] 1.44-2.54) for dioxins, 2.39 (95% CI 1.86-3.08) for total PCBs, and 2.30 (95% CI 1.81-2.93) for chlorinated pesticides. Urinary concentrations of BPA and phthalates were also associated with T2D risk; comparing the highest to lowest concentration categories, the pooled RR were 1.45 (95% CI 1.13-1.87) for BPA and 1.48 (95% CI 0.98-2.25) for phthalates. Further, EDC concentrations were associated with indicators of impaired fasting glucose and insulin resistance. Conclusions Persistent and non-persistent EDCs may affect the risk of T2D. There is an urgent need for further investigation of EDCs, especially non-persistent ones, and T2D risk in large prospective studies. [ABSTRACT FROM AUTHOR]

Endocrine disrupting chemicals (EDCs) are widespread environmental contaminants that affect many neuroendocrine functions. The brain is particularly vulnerable to EDCs during critical periods of gestational development when gonadal hormones exert organizational effects on sexually dimorphic behaviors later in life. Peripubertal development is also a time of continued neural sensitivity to organizing effects of hormones, yet little is known about EDC actions at these times. We sought to determine effects of prenatal or juvenile exposures to a class of EDCs, polychlorinated biphenyls (PCBs) at human-relevant dosages on development, physiology, and social and anxiety-related behaviors later in life, and the consequences of a second juvenile “hit” following prenatal treatment. We exposed male and female Sprague–Dawley rats to PCBs (Aroclor 1221, 1 mg/kg/day, ip injection) and/or vehicle during prenatal development (embryonic days 16, 18, 20), juvenile development (postnatal days 24, 26, 28), or both. These exposures had differential effects on behaviors in sex and age-dependent ways; while prenatal exposure had more effects than juvenile, juvenile exposure often modified or unmasked the effects of the first hit. Additionally, females exhibited altered social and anxiety behavior in adolescence, while males displayed small but significant changes in sociosexual orientation in adulthood. Thus, the brain continues to be sensitive to organizing effects of EDCs through juvenile development. As humans are exposed to EDCs throughout multiple periods in their life, these findings have implications for our understanding of EDC effects on physiology and behavior. [ABSTRACT FROM AUTHOR]

Throughout human life, an extensive and varied range of emerging environmental contaminants, called endocrine disruptors (EDCs), cause adverse health effects, including in the cardiovascular (CV) system. Cardiovascular diseases (CVD) are worryingly one of the leading causes of all mortality and mobility worldwide. The UV-B filter octylmethoxycinnamate (also designated octinoxate, or ethylhexyl methoxycinnamate (CAS number: 5466-77-3)) is an EDC widely present in all personal care products. However, to date, there are no studies evaluating the OMC-induced effects on vasculature using animal models to improve human cardiovascular health. This work analysed the effects of OMC on rat aorta vasculature and explored the modes of action implicated in these effects. Our results indicated that OMC relaxes the rat aorta by endothelium-dependent mechanisms through the signaling pathways of cyclic nucleotides and by endothelium-independent mechanisms involving inhibition of L-Type voltage-operated Ca2+ channels (L-Type VOCC). Overall, OMC toxicity on rat aorta may produce hypotension via vasodilation due to excessive NO release and blockade of L-Type VOCC. Moreover, the OMC-induced endothelial dysfunction may also occur by promoting the endothelial release of endothelin-1. Therefore, our findings demonstrate that exposure to OMC alters the reactivity of the rat aorta and highlight that long-term OMC exposure may increase the risk of human CV diseases. [Display omitted] • OMC relaxes the rat aorta by endothelium-dependent and -independent pathways. • The endothelium-dependent vasodilation is mediated by cyclic nucleotides. • The endothelium-independent vasodilation involves an inhibition of L-Type VOCC. • OMC alters the reactivity of rat aorta contributing to endothelial dysfunction. • The exposure to OMC may increase the risk of human cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Exposures to polychlorinated biphenyls (PCBs) during early development have long-lasting, sexually dimorphic consequences on adult brain and behavior. However, few studies have investigated their effects during juvenile development, a time when increases in pubertal hormones influence brain maturation. Here, male and female Sprague Dawley rats were exposed to PCBs (Aroclor 1221, 1 mg/kg/day) or vehicle prenatally, during juvenile development, or both, and their effects on serum hormone concentrations, gene expression, and DNA methylation were assessed in adulthood. Gene expression in male but not female brains was affected by 2-hits of PCBs, a result that paralleled behavioral effects of PCBs. Furthermore, the second hit often changed the effects of a first hit in complex ways. Thus, PCB exposures during critical fetal and juvenile developmental periods result in unique neuromolecular phenotypes, with males most vulnerable to the treatments. [ABSTRACT FROM AUTHOR]

Human and livestock excretions contain appreciable quantities of natural estrogens, namely, estrone (E1), 17β-estradiol (E2), estriol (E3), and 17α-estradiol (17α). E2 is the most abundant and the most potent natural estrogen, which can disrupt endocrine system even at ng/L scale. The authors investigated the feasibility of ultrasonic irradiation for E2 removal. The degradation of E2 followed pseudo first-order kinetics. The rate constant increased as the ultrasonic density increased up to 840 W/L. The removal coefficient was maintained at 0.34 ± 0.03 min −1 at initial E2 concentration from 1 to 50 μg/L. The removal reaction was independent of pH values, carbonate and humic acid in typical ranges of river water, groundwater, and effluent of wastewater treatment plant. E2 would be degraded by thermal reactions near the cavity–liquid interface. E1 and E3, endocrine-disrupting intermediates, were not detected during the ultrasonic degradation of E2. Ultrasonic degradation would be efficient for destruction of 17-β estradiol in aqueous solutions. [ABSTRACT FROM AUTHOR]

Treatment of endocrine-disrupting chemical (EDC) from aqueous solution was studied using electrocoagulation followed by electrochemical oxidation techniques. An aqueous solution of bisphenol-A (BPA) was used as the model contaminant of EDC. The present experimental study has revealed two major treatment techniques such as electrocoagulation followed by electrochemical oxidation processes. These two treatments can be operated independently in batch mode processes. In the first stage, the aqueous BPA solution was subjected to the electrocoagulation under various operating conditions. In electrocoagulation, aluminum (Al) electrode, at the current density of 12 mA cm−2, 56.12% of chemical oxygen demands (COD) removal was achieved in a relatively short treatment time of 20 min. After completion of electrocoagulation, the sample was then subjected to electrochemical oxidation with different current density. In the electrochemical oxidation, complete COD removal could be achieved at current density of 12 mA cm−2 within 50 min of treatment time. Kinetic analysis indicates that the removal rate might be obeyed as a first order model. The results of UV–vis spectrum showed that at the end of the treatment, BPA compound was completely removed from the aqueous solution. Electrochemically produced sludge was characterized using fourier transform infra red spectroscopy. [ABSTRACT FROM AUTHOR]

This article presents an overview of the analytical methods for the determination of target endocrine-disrupting chemicals (EDCs) in airborne particles. Among EDCs, we selected four important groups of compounds (alkylphenols, bisphenol A, phthalates, and natural and synthetic sex hormones) because of their worldwide production, environmental ubiquity and toxicity. Due to their physical and chemical properties (high molecular weight, low/medium polarity and volatility), these EDCs can be present in the atmosphere mainly associated with particulate matter. EDCs linked to small particles (PM 10 and PM 2.5 ) can penetrate into the respiratory system and damage human health. We discuss aspects of analytical methodology, such as sampling, extraction, and determination. We review levels found in outdoor and indoor samples. According to the results reported, human exposure to these compounds, especially in indoor environments, should be investigated in more depth, since some compounds, such as dibutyl phthalate and diethyl phthalate, reach levels of µg/m 3 . [ABSTRACT FROM AUTHOR]

Anogenital distance (AGD), a useful anthropometric measurement for genital development in both animals and humans, was originally found by reproductive toxicologists in rodent experiments. As an easy-to-measure and sensitive marker, AGD has become a bioassay of fetal androgen action and a well-established reproductive toxicity endpoint in animals. It is generally accepted that AGD is sexually dimorphic in many mammals, with males having longer AGD than females. Exposure to proposed endocrine disruptors may result in reduced AGD; thus, it has been used to measure health effects of compounds with endocrine-altering properties or endocrine-disrupting chemicals (EDCs) in environmental toxicology. Moreover, AGD is an important clinical measure to address endocrine-sensitive endpoints in the first year of life and to assess the adverse impact of in utero exposure to environmental EDCs. Recently, AGD has been identified as one of the endpoints in the US Environmental Protection Agency guidelines for reproductive toxicity studies in humans, but use of AGD in human studies is still rare, and the results remain mixed and inconclusive due to many reasons. In order to achieve a breakthrough, researchers are endeavoring to standardize the measurement of AGD, normalize age-specific population data in different ethnic groups, and conduct more in-depth human researches in this field. [ABSTRACT FROM AUTHOR]

During recent decades more than 100,000 new chemicals have been introduced as common consumer products into our environment. Among these chemicals, endocrine-disrupting chemicals (EDCs) are of particular concern owing to their toxicity in animal studies and their impacts on human health. EDCs are ubiquitous in the environment, including the air, water, and soil. The endocrine-disrupting effect of EDCs has been found to imitate the action of steroid hormones and promote several endocrine and reproductive disorders in both animal and human studies. In the present review, we focus on the effects of EDCs on the immune system. EDCs interfere with the synthesis of cytokines, immunoglobulins, and inflammatory mediators, and they also affect the activation and survival of immune cells. The dysfunction of the immune system caused by EDCs may lead to the attenuation of immunity (immunodeficiency) against infection or hyperreactivity of immune responses (allergy and autoimmune disease). In this review, we summarize epidemiologic, animal, and cell studies to demonstrate the potential effects of EDCs on immunity, allergy, and autoimmune diseases. We also address the impact of EDCs on epigenetic regulation.

The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)—two major alkylphenols—have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation.

The existing study deals with adsorptive removal of the endocrine-disrupting chemical bisphenol-A and toxic azo dye solvent black-3 from single and binary solutions. These two chemicals are commonly used as an additive in the synthetic plastic industries. Among the tested twenty pristine and modified biochars, the pristine pinecone biochar produced at 750 °C revealed greater bisphenol-A removal. Simulation of the experimental data obtained for bisphenol-A and dye removal from the single-component solution offered a best-fit to Elovich (R2 > 0.98) and pseudo-second-order (R2 > 0.99) kinetic models, respectively. Whereas for the bisphenol-A + dye removal from binary solution, the values for bisphenol-A adsorption were best suited to Elovich (R2 > 0.98), while pseudo-second-order (R2 > 0.99) for dye removal. Similarly, the two-compartment model also demonstrated better values (R2 > 0.92) for bisphenol-A and dye removal from single and binary solutions with greater F fast values (except for bisphenol-A in binary solution). The Langmuir isotherm model demonstrated the highest regression coefficient values (R2 > 0.99) for bisphenol-A and dye removal with the highest adsorption capacity of 38.387 mg g−1 and 346.856 mg g−1, correspondingly. Besides, the co-existence of humic acid revealed a positive impact on bisphenol-A removal, while the dye removal rate was slightly hindered in presence of humic acid. The absorption process showed monolayer coverage of biochar surface with contaminants using a chemisorption mechanism with fast reactions between functional groups on the adsorbate and adsorbent. Whereas the adsorption mechanism was primarily controlled by hydrogen bonding, hydrophobic and π-π electron-donor-acceptor interactions as confirmed by FTIR, XPS, and pH investigations. [Display omitted] • Among twenty tested biochars, pinecone biochar (750 °C) showed higher BPA removal. • Pinecone biochar revealed BPA and azo dye removal from single and binary solutions. • Elovich and pseudo-second-order were the best-suited models for BPA and dye removal. • Co-existence of humic acid enhanced BPA removal, while dye removal rate was impeded. • Synthetic plastic components BPA and solvent black-3 dye were significantly removed. [ABSTRACT FROM AUTHOR]

Behavioural syndromes have received much attention by behavioural ecologists in recent years. While the relationship between boldness across contexts and between boldness and aggression are frequently investigated, little is known about how these relationships might change because of environmental disturbances such as exposure to endocrine disrupters. 17α-ethinyloestradiol (EE2) is an oestrogen mimic that is prevalent in aquatic ecosystems worldwide and has severe, negative impacts on the behaviour and physiology of exposed organisms. To assess how EE2 affects boldness and decision making, male Siamese fighting fish, Betta splendens, received repeated trials of three boldness assays (novel environment, empty tank and novel object) and one decision-making assay (a dummy male and female presented simultaneously) before and after exposure to acute, nominal doses of EE2. A control group of males received the same number of trials but was not exposed to EE2. When subjects were unexposed, a behavioural syndrome was found for boldness across contexts. In addition, boldness was positively correlated with aggression in the decision-making context. EE2 exposure disrupted this behavioural syndrome. In summary, EE2 exposure reduced overall behavioural response in all contexts, disrupted the behavioural syndrome and reduced behavioural consistency. Thus, even nominal, short-term exposure to EE2 can have dramatic effects on multiple levels of behaviour and potentially generate severe fitness consequences on exposed aquatic species. This study provides the first evidence of a boldness–aggression syndrome in this species and demonstrates that pollution may negatively influence consistent individual differences in behaviour. [Copyright &y& Elsevier]

Abstract: ZnO hierarchical micro/nanospheres were successfully synthesized via a facile and surfactant-free chemical solution route. The field emission scanning electron microscopy and transmission electron microscopy observations showed that the ZnO micro/nanospheres were assembled by large amounts of interleaving nanosheets with the thickness of about 17nm. The X-ray diffraction, energy dispersion X-ray and Raman results revealed that the as-synthesized products were well-crystalline and possessing wurtzite hexagonal phase pure ZnO. Under UV irradiation, the ZnO micro/nanospheres showed an enhanced photocatalytic performance compared with the ZnO nanorods and commercial TiO2 in the degradation of phenol. The photocatalytic enhancement of ZnO micro/nanospheres was attributed to their unique hierarchical porous surface structure and large surface area which can enhance the electron–hole separation and increased the yield of hydroxyl radical quantities as evidenced by the photoluminescence spectra. By using a certain of radical scavengers, hydroxyl radical was determined to play a pivotal role for the phenol degradation. Moreover, the as-synthesized ZnO micro/nanospheres could be easily recycled without any significant loss of the photocatalytic activity. Other endocrine-disrupting chemicals such as resorcinol, bisphenol A and methylparaben were also successfully photodegraded under identical conditions. These characteristics showed the practical applications of the ZnO micro/nanospheres in environmental remediation. [Copyright &y& Elsevier]