Doses Of Bisphenol Research Articles

Bisphenol S Exposure Perturbs Epididymis Function of Adult Male Golden Hamster, <i>Mesocricetus auratus</i>

Bisphenols are widely used in industrial and commercial products that exhibit endocrine-disrupting properties. Bisphenol S (BPS) has been reported to show adverse impact on human health. The objective of the present study was to examine the effect of BPS on epididymal function in the adult male golden hamster Mesocricetus auratus. Different doses of BPS (25, 50 and 75mg/kg BW/day) were orally administered for 28 days. BPS administration caused a reduction in body and epididymis weight, sperm count and sperm viability. BPS exposure also caused a reduction in the serum testosterone levels, suggesting its impact on testicular steroidogenesis. Further, the activities of antioxidant enzymes (SOD and catalase) in the epididymis were markedly decreased, while the levels of lipid peroxidation increased significantly in epididymis of BPStreated hamsters. Epididymides obtained from BPS treated hamsters showed degenerative changes in the caput, corpus and cauda along with a decreased sperm count in the lumen. In conclusion, we demonstrate that exposure to BPS caused oxidative stress in the epididymis, which may lead to impaired reproductive function.

Reproductive and transgenerational toxicity of bisphenol S exposure in pregnant rats: Insights into hormonal imbalance and steroid biosynthesis pathway disruption

Bisphenol S (BPS) is an alternative chemical to bisphenol A commonly used in food packaging materials. It raises concerns due to potential adverse effects on human health. However, limited evidence exists regarding reproductive toxicity from BPS exposure, and the mechanism of associated transgenerational toxicity remains unclear. In this study, pregnant SD rats were exposed to two different doses of BPS (0.05 or 20 mg/kg) from GD6 to PND21. The objective was to investigate reproductive and transmissible toxicity induced by BPS, explore endocrine effects, and uncover potential underlying mechanisms in rats. Perinatal exposure to BPS in the F0 generation significantly decreased the rate of body weight, ovarian organ coefficient, and growth and development of the F1 generation. Notably, these changes included abnormal increases in body weight and length, estrous cycle disruption, and embryonic dysplasia in F1. 4D-DIA proteomic and PRM analyses revealed that exposure to 20 mg/kg group significantly altered the expression of proteins, such as Lhcgr and Akr1c3, within the steroid biosynthetic pathway. This led to elevated levels of FSH and LH in the blood. The hypothalamic-pituitary-ovarian (HPO) axis, responsible for promoting fertility through the cyclic secretion of gonadotropins and steroid hormones, was affected. RT–qPCR and Western blot results demonstrated that the expression of GnRH in the hypothalamus was decreased, the GnRHR in the pituitary gland was decreased, and the expression of FSHβ and LHβ in the pituitary gland was increased. Overall, BPS exposure disrupts the HPO axis, hormone levels, and steroid biosynthesis in the ovaries, affecting offspring development and fertility. This study provides new insights into the potential effects of BPS exposure on the reproductive function of the body and its relevant mechanisms of action.

The effect of bisphenol A on antioxidant defense and the structure and function of the liver of Siberian sturgeon (Acipenser baerii).

The present study was conducted to investigate the biochemical and histological changes of liver tissue in Siberian sturgeon (Acipenser baerii) exposed to different doses of bisphenol A (BPA). One hundred and eighty pieces of 1-year-old A. baerii with an average weight of 200-250 g bought and randomly distributed in 18 tanks (n = 10). After 2 weeks of adaptation, the fish received intraperitoneal injections of 1, 10, and 100 μg/g/week BPA and μg/g/week of 17β-estradiol intraperitoneally. The solvent control group received only peanut oil, while the control group did not receive any injections. In order to investigate histological changes of the liver, after 2 weeks the liver samples were taken, fixed in 10% formalin solution and slides prepared by routine histological methods. For assaying antioxidant defense status, the liver tissue from three fish of each replicates was captured and after homogenization, activity of catalase, superoxide dismutase, and glutathione peroxidase and malondialdehyde measured. The most important histological changes observed in the liver tissue were: vacuolation of hepatocytes, nuclear hypertrophy, necrosis of liver cells, expansion of sinusoids, and accumulation of fat cells. In the highest dose, the intensity of tissue changes increased. Activity of antioxidant enzymes and malondialdehyde content increased in fish exposed to 100 μg/g/week BPA in compare with other groups (p < .05). According to our findings, it could be concluded that liver histology was affected by BPA and tissue damage had occurred, which had led to changes in blood parameters. Also, the obtained results showed that the high concentrations of BPA used in this study stimulate the antioxidant defense. RESEARCH HIGHLIGHTS: BPA evoke oxidative stress in Siberian sturgeons in high dose of exposure. Severity of liver histologic lesions was dose dependent.

Effect of different doses of Bisphenol A on albino rats' liver: Histological and immunohistochemical study

Effect of different doses of Bisphenol A on albino rats' liver: Histological and immunohistochemical study

Antenatal Exposure to Plastic Pollutants: Study of the Bisphenols and Perfluoroalkyls Effects on Human Stem Cell Models

Endocrine disruptors (EDs), such as Bisphenols (BPs) and Perfluoroalkyls (PFs), are a class of plastic pollutants widely used in industrial applications. Human exposure to these molecules usually occurs through ingestion of contaminated food and water. Once entered the human body they can interfere with endogenous hormone signaling, leading to a wide spectrum of diseases. It has been reported that BPs and PFs can cross the placental barrier accumulating in the fetal serum, but the detrimental consequences for human development remain to be clarified. Here we analyze the effects of different doses of bisphenol A and S (BPA, BPS) perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on proliferation and mitochondrial health on different types of stem cells: through an integrated approach that combines data from pluripotent stem cells (hiPSCs) with that from the “environment” in which the embryo develops (fetal annexes-derived perinatal stem cells) we verified the potential developmental toxicity of the in utero EDs exposure. Data obtained showed that overall, BPs, and PFs tended to increase the proliferation rate of perinatal stem cells; a similar response was observed in hiPSCs exposed to very low doses of BPs and PFs, while at higher concentrations these chemicals were toxic; in addition, both the BPs and the PFs exerted a mitotoxic effects hiPSCs at all the concentration studied. All these data suggest that antenatal exposure to BPs and PFs, also at very low concentrations, may modify the biological characteristics of stem cells present in both the developing fetus and the fetal annexes, thus perturbing normal human development.

Bisphenols as promoters of the dysregulation of cellular junction proteins of the blood-testis barrier in experimental animals: A systematic review of the literature.

Daily, people are exposed to chemicals and environmental compounds such as bisphenols (BPs). These substances are present in more than 80% of human fluids. Human exposure to BPs is associated with male reproductive health disorders. Some of the main targets of BPs are intercellular junction proteins of the blood-testis barrier (BTB) in Sertoli cells because BPs alter the expression or induce aberrant localization of these proteins. In this systematic review, we explore the effects of BP exposure on the expression of BTB junction proteins and the characteristics of in vivo studies to identify potential gaps and priorities for future research. To this end, we conducted a systematic review of articles. Thirteen studies met our inclusion criteria. In most studies, animals treated with bisphenol-A (BPA) showed decreased occludin expression at all tested doses. However, bisphenol-AF treatment did not alter occludin expression. Cx43, ZO-1, β-catenin, nectin-3, cortactin, paladin, and claudin-11 expression also decreased in some tested doses of BP, while N-cadherin and FAK expression increased. BP treatment did not alter the expression of α and γ catenin, E-cadherin, JAM-A, and Arp 3. However, the expression of all these proteins was altered when BPA was administered to neonatal rodents in microgram doses. The results show significant heterogeneity between studies. Thus, it is necessary to perform more research to characterize the changes in BTB protein expression induced by BPs in animals to highlight future research directions that can inform the evaluation of risk of toxicity in humans.

Different types of bisphenols alter ovarian steroidogenesis: Special attention to BPA

Endocrine disruptors such as bisphenol A (BPA) and some of its analogues, including BPS, BPAF, and BPE, are used extensively in the manufacture of plastics. These synthetic chemicals could seriously alter the functionality of the female reproductive system. Although the number of studies conducted on other types of bisphenols is smaller than the number of studies on BPA, the purpose of this review study was to evaluate the effects of bisphenol compounds, particularly BPA, on hormone production and on genes involved in ovarian steroidogenesis in both in vitro (human and animal cell lines) and in vivo (animal models) studies.The current data show that exposure to bisphenol compounds has adverse effects on ovarian steroidogenesis. For example, BPA, BPS, and BPAF can alter the normal function of the hypothalamic-pituitary-gonadal (HPG) axis by targeting kisspeptin neurons involved in steroid feedback signals to gonadotropin-releasing hormone (GnRH) cells, resulting in abnormal production of LH and FSH. Exposure to BPA, BPS, BPF, and BPB had adverse effects on the release of some hormones, namely 17-β-estradiol (E2), progesterone (P4), and testosterone (T). BPA, BPE, BPS, BPF, and BPAF are also capable of negatively altering the transcription of a number of genes involved in ovarian steroidogenesis, such as the steroidogenic acute regulatory protein (StAR, involved in the transfer of cholesterol from the outer to the inner mitochondrial membrane, where the steroidogenesis process begins), cytochrome P450 family 17 subfamily A member 1 (Cyp17a1, which is involved in the biosynthesis of androgens such as testosterone), 3 beta-hydroxysteroid dehydrogenase enzyme (3β-HSD, involved in the biosynthesis of P4), and cytochrome P450 family 19 subfamily A member 1 (Cyp19a1, involved in the biosynthesis of E2). Exposure to BPA, BPB, BPF, and BPS at prenatal or prepubertal stages could decrease the number of antral follicles by activating apoptosis and autophagy pathways, resulting in decreased production of E2 and P4 by granulosa cells (GCs) and theca cells (TCs), respectively. BPA and BPS impair ovarian steroidogenesis by reducing the function of some important cell receptors such as estrogens (ERs, including ERα and ERβ), progesterone (PgR), the orphan estrogen receptor gamma (ERRγ), the androgen receptor (AR), the G protein-coupled estrogen receptor (GPER), the FSHR (follicle-stimulating hormone receptor), and the LHCGR (luteinizing hormone/choriogonadotropin receptor). In animal models, the effects of bisphenol compounds depend on the type of animals, their age, and the duration and dose of bisphenols, while in cell line studies the duration and doses of bisphenols are the matter.

Bisphenol S Increases Cell Number and Stimulates Migration of Endometrial Epithelial Cells.

To determine whether bisphenol S (BPS), a common substitute for bisphenol A (BPA), induces cell proliferation and migration in human endometrial epithelial cells (Ishikawa) and adult mouse uterine tissues. Human endometrial Ishikawa cells were exposed to low doses of BPS (1 nM and 100 nM) for 72 hours. Cell proliferation was assessed through the viability assays MTT and CellTiter-Glo®. Wound healing assays were also used to evaluate the migration potential of the cell line. The expression of genes related to proliferation and migration was also determined. Similarly, adult mice were exposed to BPS at a dose of 30 mg/kg body weight/day for 21 days, after which, the uterus was sent for histopathologic assessment. BPS increased cell number and stimulated migration in Ishikawa cells, in association with the upregulation of estrogen receptor beta (ESR2) and vimentin (VIM). In addition, mice exposed to BPS showed a significantly higher mean number of endometrial glands within the endometrium. Overall, in vitro and in vivo results obtained in this study showed that BPS could significantly promote endometrial epithelial cell proliferation and migration, a phenotype also observed with BPA exposure. Hence, the use of BPS in BPA-free products must be reassessed, as it may pose adverse reproductive health effects to humans.

Preconceptional exposure of adult male rats to bisphenol S impairs insulin sensitivity and glucose tolerance in their male offspring

Since the use of bisphenol A (BPA) has been restricted because of its endocrine disruptor properties, bisphenol S (BPS) has been widely used as a substitute of BPA. However, BPS exerts similar effects on metabolic health as BPA. The effects of maternal exposure to BPA and BPS on the metabolic health of offspring have been largely documented during the past decade. However, the impact of preconceptional paternal exposure to BPS on progenies remains unexplored. In this study we investigated the impact of paternal exposure to BPS before conception, on the metabolic phenotype of offspring. Male Wistar rats were administered BPS through drinking water at the dose of 4 μg/kg/day (BPS-4 sires) or 40 μg/kg/day (BPS-40 sires) for 2 months before mating with females. The progenies (F1) were studied at fetal stage and in adulthood. We showed that preconceptional paternal exposure to BPS for 2 months did not alter the metabolic status of sires. The female offspring of sires exposed to lower or higher doses of BPS showed no alteration of their metabolic phenotype compared to females from control sires. In contrast, male offspring of BPS-4 sires exhibited increased body weight and body fat/lean ratio, decreased insulin sensitivity and increased glucose-induced insulin secretion at adult age, compared to the male offspring of control sires. Moreover, male offspring of BPS-4 sires developed glucose intolerance later in life. None of these effects were apparent in male offspring of BPS-40 sires. In conclusion, our study provides the first evidence of the non-monotonic and sex-specific effects of preconceptional paternal exposure to BPS on the metabolic health of offspring, suggesting that BPS is not a safe BPA substitute regarding the inter-generational transmission of metabolic disorders through the paternal lineage.

Disturbance in Some Fertility Biomarkers Induced and Changes in Testis Architecture by Chronic Exposure to Various Dosages of Each of Nonylphenol or Bisphenol A and Their Mix.

Simple SummaryIn this study, 70 male albino rats were allocated to the control group (GI) and were given 1 mL of ethanol; G, II, and G III were treated with 100 mg/Kg of each of BPA and NP, G IV and G V were treated with 25 mg/Kg of each of BPA and NP, G VI was given a mixture of a high dose of BPA and NP, and G VII was given a mixture of a low dose of BPA and NP. A significant elevation in the TNF Alpha, TNF Beta, and Caspase 3 serum was recorded individually and in the groups treated with high doses. In conclusion, exposure to BPA and NP strongly impacts antioxidants, immune-inflammatory mediators, and testicular tissue architecture. Furthermore, the data from this investigation support the idea that exposure to BPA and NP in daily life has multiple damages.This investigation was conducted to demonstrate the potential impacts of different doses of Bisphenol A (BPA) or Nonylphenol (NP) and their mixtures on some biological activities in male albino rats. Seventy male albino rats were allocated to the control group (GI) and were given 1 mL of ethanol. G II and G III were given 100 mg/kg of each of BPA and NP, G IV and G V were given 25 mg/kg of each of BPA and NP, G VI was given a high dose of BPA and NP, and G VII was given a low dose of BPA and NP. All animals were treated orally for 60 days. Serum biomarkers of oxidative stress, antioxidants, immune-inflammatory mediators, and apoptotic markers were determined, as well as a histopathological examination of the testis at the end of the experimental period. The results obtained showed a pronounced increase in malondialdehyde (MDA), protein carbonyl (PC), and 4-hydroxynonenol (4-HNE), concomitant with a significant reduction in serum Superoxide dismutase (SOD), catalase enzyme (CAT), and total antioxidant capacity (TAC) in all treated groups. A significant elevation in TNF Alpha, TNF Beta, and Caspase 3 serum was recorded individually and in the groups treated with high doses. The disturbance is represented by histological damage in the testis in the germinal epithelium and a decrease in spermatozoa inside the lumen of seminiferous tubules. The effects on testis tissues were dose-dependent, pronounced in mixture doses, and remarkable in higher doses. In conclusion, exposure to BPA and NP strongly impacts antioxidants, immune-inflammatory mediators, and testis tissue architecture. Furthermore, the data from this investigation support the idea that exposure to BPA and NP in daily life has multiple damages.

Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis.

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.

Bisphenol S induced dysregulations in liver; iron regulatory genes and inflammatory mediators in male Wistar rats.

Bisphenol S (BPS), an analog of bisphenol A (BPA), has been frequently detected in consumer products, food wrappers, plastics, and thermal papers. Since the liver is a hub of metabolic and detoxification pathways, thus intimately related to BPS presence in the environment and body. The current study was designed to investigate the effects of BPS administration in an animal model. Twenty-five male Wistar rats weighing 175 ± 25 g were randomly divided into control and treated groups. The control group was further divided into group I (no treatment) and group II (corn oil), whereas the treatment group was divided into D-I (40 mg/kg/day), D-II (200 mg/kg/day), and D-III (400 mg/kg/day) groups, getting oral doses of BPS for 15 days. Data analysis showed a significant statistical increase in hepatic enzymes ALT (33.4%), AST (25.4%), and ALP (529.6%) in the D-III group along with the development of hypercholesterolemia and hypertriglyceridemia in all BPS groups. Aberrant mRNA expressions of some key hepatic iron regulatory genes and inflammatory mediators were evident through qRT-PCR. Bisphenol S caused congestion of central vein from mild to moderate in hepatic sections. In conclusion, our investigation insinuates BPS intoxication potential and therefore may not be a safe alternative to BPA.

Maternal perinatal exposure to bisphenol S induces an estrogenic like effect in glucose homeostasis in male offspring.

Bisphenol S (BPS) has been introduced into the industry as a safer alternative to bisphenol A (BPA). However, the recent studies have reported a possible association between BPS and disturbed glucose homeostasis, indicating that it may be a risk factor for type 1 and type 2 diabetes mellitus, obesity, and gestational diabetes mellitus. Nevertheless, the role of BPS in glucose metabolism remains controversial. In this study, we investigated the glucose metabolism of male Wistar rats born from dams that were BPS‐exposed (groups: BPS‐L (0.05 mg/kg/day), BPS‐H (20 mg/kg/day)) during pregnancy and lactation. We observed that both BPS treated groups of animals presented a significant decrease in anogenital distance/weight1/3, as compared to control animals, although no alterations in testosterone levels were observed. Furthermore, the BPS‐L group presented a significant decrease in body weight from postnatal day (PND) 21 to adult stage. In addition, a significant increase in glucose tolerance, pancreatic β‐cell proliferation, the frequency of small islets, and the average β‐cell size at PND 36 was observed in this group. However, no changes in insulin serum levels and percentage of β‐cells were recorded. Furthermore, these changes were not preserved at the adult stage (PND 120). The results suggest that the administration of low doses of BPS during the perinatal period induced an estrogenic like effect, with males apparently becoming more female‐like in their responses to a glucose challenge.

Exposure to a "safe" dose of environmental pollutant bisphenol A elevates oxidative stress and modulates vasoactive system in hypertensive rats.

Due to the prevalence of hypertension (one of the major risk factors of CVD) in the population, it is necessary to explore the adverse effects of daily tolerable and "safe" dose of bisphenol A (BPA) under hypertensive conditions. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME, 40mg/kg b.w/day) induced hypertensive Wistar rats to BPA (50μg/kg b.w/day) by oral administration along with appropriate controls for 30days period. The results illustrate that a 'safe' dose of BPA does not influence the systolic blood pressure (SBP) and levels of circulatory biomarkers of tissue damage. On the other hand, BPA exposure significantly (p < 0.05) elevates the thiobarbituric acid reactive substances (TBARS) content in plasma and tissues (heart, aorta, liver and kidney) in hypertensive rats when compared with respective control (BPA alone exposed) rats. Similarly, a significant modulation of ROS generation in RBC, plasma nitric oxide (NO) level and angiotensin-converting enzyme (ACE) activity was observed only under hypertensive milieu. In conclusion, the observed adverse effects during 'safe' dose of BPA exposure are specific to the hypertensive condition. Therefore, a precise investigation to explore the effects of BPA exposure in vulnerable hypertensive populations is highly suggested.

Effects of chronic exposure to usual and high doses of Bisphenol A on cardiac arrhythmias, electrophysiology, and autonomic modulation

Abstract Background Bisphenol A (BPA) is a synthetic compound found in plastic bottles, sports equipment, or water pipes. The continuous and inevitable human exposure to BPA has been related to increased cardiovascular risk. In experimental studies, acute exposure to high BPA doses was associated with ventricular arrhythmias. However, the effects of chronic exposure to usual BPA doses (i.e., relevant for usual human exposure) on cardiac arrhythmogenicity have not been properly assessed. Purpose We aimed to assess the effects of chronic exposure to high and usual BPA doses on cardiac arrhythmias, electrophysiology, and autonomic modulation in rats. Methods Adult female Wistar rats were randomized into 3 groups: Control, BPA, and BPA-HD (n=7 each). BPA and BPA-HD rats received 50 μg/kg/day and 25 mg/kg/day of BPA, respectively, for 9 weeks. Rats were implanted with radiotelemetry ECG devices and 24-h ECG recordings were performed prior to and after application of transesophageal atrial burst pacing (4,000 stimuli/min for 20 s; 15 cycles). Heart rate variability (HRV) parameters and atrial and ventricular arrhythmias (i.e., atrial premature beats [APB], atrial fibrillation [AF], ventricular premature beats [VPB], ventricular tachycardia/fibrillation [VT/VF]) were assessed based on the 24-h ECG recordings. The left atrium was then collected and atrial depolarization velocity and action potential duration to 90% (APD90) and 50% (APD50) of complete repolarization were measured. Results Mean heart rate (p=0.48), the number of VPB (p=0.90), AF inducibility (p=0.68), and atrial action potential parameters (all p&amp;gt;0.05) were all similar between the 3 groups. None of the animals presented VT/VF. There was no significant difference in the number of atrial or ventricular arrhythmic events nor in the HRV parameters between BPA and Control (all p&amp;gt;0.05). However, BPA-HD presented a significantly higher number of APB both prior to (p=0.02) and after (p=0.04) atrial pacing, and a significantly higher number of post-pacing spontaneous AF episodes (p&amp;lt;0.01) compared to Control. The parasympathetic indexes SDNN, RMSSD, pNN5, and the NHF of the HRV spectrum were all significantly higher (all p&amp;lt;0.05), whereas the LF/HF ratio, an index of sympathetic and parasympathetic interactions, was significantly lower (p=0.01) in the BPA-HD compared with the Control rats. Conclusions In rats, chronic exposure to BPA doses relevant for usual human exposure was not associated in any significant change in cardiac arrhythmogenicity, electrophysiology, or autonomic modulation. However, high-dose BPA exposure, such as that occurring in workers in the plastics industry, led to significant increase in atrial arrhythmogenicity, including AF, that did not seem to be related to atrial electrophysiology changes. Instead, given the strong atrial proarrhythmic effects of vagal hyperactivity, this effect could be linked to the significant increase in vagal modulation induced by high-dose BPA exposure. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS – UEFISCDI

2-month exposure to a low dose of bisphenol A does not alter femur growth in young rams (Ovis aries)

2-month exposure to a low dose of bisphenol A does not alter femur growth in young rams (Ovis aries)

Study of subacute renal toxicity of Bisphenol A in rats

Background and Aims: Bisphenol A (BPA) falls in the category of hormonal disruptors due to its widespread application, and several studies have revealed its toxicity in different doses. However, few studies have investigated the effect of BPA on the renal system. Therefore, the present study aimed to investigate the effect of BPA on renal system function in rats. Materials and Methods: Initially, the rats were divided into 6 groups (n=6). Group 1 received only the carrier substance. The rats in the second to sixth groups were gavaged with BPA in 0.1, 1, 10, 50, and, 100 mg/kg/BW/day doses for 29 days, respectively. On the 30th day, blood samples were taken from the heart and kidney tissues were separated after collecting 24 h urine. Biochemical parameters including urea, creatinine, total urine and serum protein, and serum albumin were measured subsequently. Eventually, kidney tissue was sent to a laboratory for histological examination. Results: There was no significant difference in serum creatinine levels in rats treated with different doses of bisphenol A. However, its level in urine increased at 50 mg/kg dose, compared to 1 and 10 mg/kg doses (P&lt;0.001). Serum and urine urea increased significantly only at of 10 mg/kg dose, compared to 1 and 0.1 mg/kg doses (P&lt;0.001). Serum albumin was reduced at 100 mg/kg dose, compared to controls. Total serum protein decreased at doses of 50 and 100 mg/kg, compared to controls and increased in urine at 50mg/kg dose (P&lt;0.001). The protein/creatinine ratio increased significantly at doses of 1 to 50 mg/kg (P&lt;0.001). Histological examination also revealed that BPA caused degenerative, infiltration, and dilation changes in kidney tissue in a dose-dependent manner. Conclusion: Based on the obtained data, BPA at 50 and 100 mg/kg concentrations could lead to kidney tissue damage in rats and subsequent renal failure.

Behavioral changes and hyperglycemia in NODEF mice following bisphenol S exposure are affected by diets

Bisphenol S (BPS), an analogue of the controversial bisphenol A (BPA) that is found in epoxy resins and plastics, is a potential endocrine-disrupting chemical that can mimic endogenous hormone signaling. However, little is known about the behavioral or immunologic effects of BPS. The purpose of this study was to examine the impact of diets in BPS-treated mice in relation to hyperglycemia, development of type 1 diabetes, immunomodulation, and behavioral changes. Adult male and female nonobese diabetic excluded flora (NODEF) mice were exposed to environmentally relevant doses of BPS (VH, 30, or 300 μg/kg BW) and fed either a soy-based diet, a phytoestrogen-free diet, or a Western diet. NODEF male mice fed a soy-based diet exhibited a decreased curiosity/desire to explore, and possibly increased anxiety-like behavior and decreased short-term memory when exposed to BPS (300 μg/kg BW). In addition, these mice had significant increases in non-fasting blood glucose levels along with increased insulin sensitivity, impaired glucose tolerance, resistance to fasting and proinflammation. Although BPS had little effect on the glucose parameters in NODEF male mice fed a Western diet, there were decreases in %CD24+CD5+ and %B220+CD40L–cell populations and increases in distance traveled during the novel object test, suggesting hyperactivity. NODEF females fed a phytoestrogen-free diet exhibited slight decreases in time spent immobile during the tail suspension test in both the 30 and 300 μg/kg BW dose groups along with increases in %CD4+CD8+ and %Mac3+CD45R+ cell populations, signifying increased hyperactivity and anxiety-like behavior. In conclusion, BPS-exposed NODEF mice exhibited sex and diet-related changes in hyperglycemia, behaviors and immune endpoints.

Individual and combined effects of BPA, BPS and BPAF on the cardiomyocyte differentiation of embryonic stem cells

Exposure to many kinds of bisphenols (BPs) is common, and the effects of BP mixtures may differ from those of individual BPs. Therefore, evaluating combined exposure effects is necessary. Our study evaluated the individual and combined exposure effects of bisphenol A (BPA), bisphenol S (BPS) and bisphenol AF (BPAF) on embryonic development using an embryonic stem cell test (EST) and a concentration additive (CA) model at relatively high doses to uncover the interaction model of the three BPs. Environmentally relevant concentrations were then used to evaluate the possible effects of the individual and combined BPs at actual human exposure levels. Exposure to relatively high-dose BPA, BPS and BPAF inhibited embryonic stem cell differentiation into cardiomyocytes and exhibited weak embryo toxicity. Individually, BPA, BPS and BPAF inhibited endoderm, mesoderm and ectoderm marker expression but enhanced pluripotency marker expression. Combined exposure to BPs had an additive effect on cardiomyocyte differentiation and embryonic stem cell proliferation based on the CA model. Environmentally relevant individual or combined BP doses (10 ng/ml individual BPA, BPS and BPAF doses or 1 ng/ml and 10 ng/ml BP mixture doses) failed to cause oxidative stress, DNA damage or apoptosis changes in stem cell differentiation. The cardiomyocyte differentiation ratio also did not change significantly. Individual and combined exposure to environmentally relevant BP doses led to a significant increase in collagen expression. BPAF and the combination of BPs increased the type 1 collagen level, while the combination also increased the type 3 collagen level, which may be related to p38 pathway activation. The p38 pathway inhibitor SB203580 inhibited the increase in collagen during cardiomyocyte differentiation caused by low-dose BPs. These results suggest that relatively high-dose BPs in combination have an additive effect on cardiomyocyte differentiation. Low-dose BPs individually and in combination may affect cardiomyocyte collagen through the p38 pathway.

Exposure to alternative bisphenols BPS and BPF through breast milk: Noxious heritage effect during nursing associated with idiopathic infertility

There is increasing evidence that bisphenols BPS and BPF, which are analogues of BPA, have deleterious effects on reproduction even at extremely low doses. Indirect exposure via the maternal route (i.e. across the placenta and/or by breastfeeding) is underestimated, although it can be assumed to be a cause of idiopathic female infertility. Therefore, we hypothesised the deleterious effects of exposure to BPA analogues during breastfeeding on the ovarian and oocyte quality of offspring. A 15-day exposure period of pups was designed, whilst nursing dams (N ≥ 6 per experimental group) were treated via drinking water with a low (0.2 ng/g body weight/day) or moderate (20 ng/g body weight/day) dose of bisphenol, mimicking real exposure in humans. Thereafter, female pups were bred to 60 days and oocytes were collected. Immature oocytes were used in the in-vitro maturation assay; alternatively, in-vivo-matured oocytes were isolated and used for parthenogenetic activation. Both in-vitro- and in-vivo-matured oocytes were subjected to immunostaining of spindle microtubules (α-tubulin) and demethylation of histone H3 on the lysine K27 (H3K27me2) residue. Although very low doses of both BPS and BPF did not affect the quality of ovarian histology, spindle formation and epigenetic signs were affected. Notably, in-vitro-matured oocytes were significantly sensitive to both doses of BPS and BPF. Although no significant differences in spindle-chromatin quality were identified in ovulated and in-vivo-matured oocytes, developmental competence was significantly damaged. Taken together, our mouse model provides evidence that bisphenol analogues represent a risk to human reproduction, possibly leading to idiopathic infertility in women.