Endocrine-disrupting chemicals (EDCs) may contribute to the rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the potential of 10 environmentally relevant EDCs to affect key events of hepatic steatosis in HepG2 human hepatoblastoma cells. Increased lipid droplet formation, a key marker of steatosis, was induced by PFOA, bisphenol F, DDE, butylparaben, and DEHP, within the non-cytotoxic concentration range of 1 nM-25 μM. Cadmium also induced this effect, but at concentrations impairing cell viability (>1 μM). At non-cytotoxic concentrations, these compounds, along with bisphenol A, dysregulated major genes controlling lipid homeostasis. Cadmium, PFOA, DDE, and DEHP significantly upregulated the DGAT1 gene involved in triglyceride synthesis, while butylparaben increased the expression of the FAT/CD36 gene responsible for fatty acid uptake. Bisphenol A downregulated the CPT1A gene involved in fatty acid oxidation. No significant effects on lipid droplet accumulation or lipid metabolism-related genes were observed for PFOS, bisphenol S, and dibutyl phthalate. Among the tested EDCs, lipid accumulation positively correlated with the expression of SREBF1, DGAT1, and CPT1A. These findings provide additional evidence that EDCs can affect MASLD and highlight the utility of in vitro methods in the screening of EDCs with hazardous steatogenic and metabolism-disrupting properties.

• Klíčová slova
• High-content imaging, In vitro testing, Lipid droplets, Metabolism-disrupting chemicals, NAFLD, NAMs,
• MeSH
• benzhydrylové sloučeniny toxicita   MeSH
• buňky Hep G2 MeSH
• diacylglycerol-O-acyltransferasa genetika   metabolismus   MeSH
• diethylhexylftalát toxicita   MeSH
• endokrinní disruptory * toxicita   MeSH
• fenoly toxicita   MeSH
• fluorokarbony toxicita   MeSH
• kapryláty toxicita   MeSH
• lidé MeSH
• metabolismus lipidů účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• ztučnělá játra * chemicky indukované   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• bisphenol A MeSH Prohlížeč
• DGAT1 protein, human MeSH Prohlížeč
• diacylglycerol-O-acyltransferasa MeSH
• diethylhexylftalát MeSH
• endokrinní disruptory * MeSH
• fenoly MeSH
• fluorokarbony MeSH
• kapryláty MeSH
• perfluorooctanoic acid MeSH Prohlížeč
• sloučeniny bisfenolu A MeSH

Bisphenol A (BPA), a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins, has been associated with a variety of adverse effects in humans including metabolic, immunological, reproductive, and neurodevelopmental effects, raising concern about its health impact. In the EU, it has been classified as toxic to reproduction and as an endocrine disruptor and was thus included in the candidate list of substances of very high concern (SVHC). On this basis, its use has been banned or restricted in some products. As a consequence, industries turned to bisphenol alternatives, such as bisphenol S (BPS) and bisphenol F (BPF), which are now found in various consumer products, as well as in human matrices at a global scale. However, due to their toxicity, these two bisphenols are in the process of being regulated. Other BPA alternatives, whose potential toxicity remains largely unknown due to a knowledge gap, have also started to be used in manufacturing processes. The gradual restriction of the use of BPA underscores the importance of understanding the potential risks associated with its alternatives to avoid regrettable substitutions. This review aims to summarize the current knowledge on the potential hazards related to BPA alternatives prioritized by European Regulatory Agencies based on their regulatory relevance and selected to be studied under the European Partnership for the Assessment of Risks from Chemicals (PARC): BPE, BPAP, BPP, BPZ, BPS-MAE, and TCBPA. The focus is on data related to toxicokinetic, endocrine disruption, immunotoxicity, developmental neurotoxicity, and genotoxicity/carcinogenicity, which were considered the most relevant endpoints to assess the hazard related to those substances. The goal here is to identify the data gaps in BPA alternatives toxicology and hence formulate the future directions that will be taken in the frame of the PARC project, which seeks also to enhance chemical risk assessment methodologies using new approach methodologies (NAMs).

• Klíčová slova
• Bisphenol A alternatives, carcinogenesis, developmental neurotoxicity, endocrine disruption, genotoxicity, human health, immunotoxicity, metabolism, toxicokinetic,
• MeSH
• benzhydrylové sloučeniny * chemie   toxicita   MeSH
• endokrinní disruptory * chemie   toxicita   MeSH
• hodnocení rizik metody   MeSH
• lidé MeSH
• sulfony toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• benzhydrylové sloučeniny * MeSH
• bisphenol A MeSH Prohlížeč
• bisphenol F MeSH Prohlížeč
• bisphenol S MeSH Prohlížeč
• endokrinní disruptory * MeSH
• sulfony MeSH

Bisphenol A alternatives are manufactured as potentially less harmful substitutes of bisphenol A (BPA) that offer similar functionality. These alternatives are already in the market, entering the environment and thus raising ecological concerns. However, it can be expected that levels of BPA alternatives will dominate in the future, they are limited information on their environmental safety. The EU PARC project highlights BPA alternatives as priority chemicals and consolidates information on BPA alternatives, with a focus on environmental relevance and on the identification of the research gaps. The review highlighted aspects and future perspectives. In brief, an extension of environmental monitoring is crucial, extending it to cover BPA alternatives to track their levels and facilitate the timely implementation of mitigation measures. The biological activity has been studied for BPA alternatives, but in a non-systematic way and prioritized a limited number of chemicals. For several BPA alternatives, the data has already provided substantial evidence regarding their potential harm to the environment. We stress the importance of conducting more comprehensive assessments that go beyond the traditional reproductive studies and focus on overlooked relevant endpoints. Future research should also consider mixture effects, realistic environmental concentrations, and the long-term consequences on biota and ecosystems.

• Klíčová slova
• BPA alternatives, Biological activity, In silico, Invertebrates, Vertebrates,
• MeSH
• benzhydrylové sloučeniny * toxicita   MeSH
• endokrinní disruptory toxicita   MeSH
• fenoly * toxicita   MeSH
• látky znečišťující životní prostředí * toxicita   MeSH
• lidé MeSH
• monitorování životního prostředí * metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• benzhydrylové sloučeniny * MeSH
• bisphenol A MeSH Prohlížeč
• endokrinní disruptory MeSH
• fenoly * MeSH
• látky znečišťující životní prostředí * MeSH

Exposure to bisphenols has been found to have adverse effects on male reproductive function in animals. Human exposure to bisphenols is widespread. Bisphenol A (BPA) and its analogues, including bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF) are utilized in various consumer products such as food contact materials and dental resins. The effects of these compounds on male fertility and spermatogenesis are unclear and findings from human studies are inconsistent. In this cross-sectional study, we evaluated the influence of BPA, BPS, BPF, BPAF (BPs) measured in semen on number of spermatozoa, total motility, progressive motility, morphology, and DNA fragmentation. We also examined the association of bisphenols (BPs) exposure with patients' occupation. A total of 358 patients aged 17-62 years with BMI 18-42 were included in the study from 2019 to 2021. BPs were extracted using solvent extraction followed by preconcentration step and determined by high-performance liquid chromatography and tandem mass spectrometry (LC/MSMS). Bisphenols were detected in 343 from 349 analysed samples (98.3% of all the samples). In 6 samples, the concentration of all BPs was under the limit of detection and in 20 samples under the limit of quantification. We did not find a statistically significant relationship between occupation and BPs. However, we observed significant correlations between the concentration of BPA and a lower motility and normal morphology. For BPS, a significant correlation with a lower ejaculate volume and a lower total sperm count was found. BPF and BPAF were detected only in 14.3% and 23.9% of samples, respectively. For BPF and BPAF, no significant correlations with spermiogram parameters were observed. Our results show that BPs are widespread in the male population (more than 90% of analysed samples), independently of an occupation and in case of BPA and BPS having a negative impact on spermiogram parameters.

• Klíčová slova
• Bisphenols, Endocrine disruptors, Human, IVF, Spermatozoa,
• MeSH
• benzhydrylové sloučeniny * toxicita   analýza   MeSH
• fenoly * MeSH
• fluorokarbony * MeSH
• lidé MeSH
• průřezové studie MeSH
• sperma * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• benzhydrylové sloučeniny * MeSH
• bisphenol A MeSH Prohlížeč
• bisphenol AF MeSH Prohlížeč
• bisphenol F MeSH Prohlížeč
• fenoly * MeSH
• fluorokarbony * MeSH

The human population is regularly exposed to bisphenols. The first compound of this class, bisphenol A, is burdened by numerous reports of its potential toxicity and has been hence replaced by its analogues, so-called next generation bisphenols. Their widespread use has made them pervasive throughout the environment. These endocrine disrupting chemicals can affect the cardiovascular system, and hence the aim of this study was to test 14 bisphenols (A, AF, AP, B, BP, C, E, F, G, M, P, PH, S and Z), and compare their effects in vitro (human and rat cell lines), ex vivo (isolated rat aorta) and in vivo (Wistar Han rats, acutely or chronically exposed to low environmental and high toxic doses). The majority of the tested bisphenols relaxed rat aorta, but their potency varied markedly. The most potent compound, bisphenol AF, had an EC50 of 57 μM. The mechanism of action was likely based on the inhibition of calcium influx via L-type calcium channels. The cytotoxicity of bisphenols towards 4 human and rat cell lines (H9c2, A-10, MCF7/S0.5 and MCF7/182R-6) showed variable potencies ranging from units of micromolar to millimolar concentrations. Based on these data, an effect on arterial blood pressure and possible cardiotoxicity was expected. Contrarily, the in vivo acute effects of three doses (0.005, 0.05 and 2.5 mg/kg) of bisphenol AF and 3 other analogues (A, S and F) on the cardiovascular system were rather biologically negligible. The most potent bisphenol, AF, was also administered chronically at a dose of 2.5 mg/kg for 4 weeks to rats, but had no impact on arterial blood pressure. Our results showed that bisphenols can relax vascular smooth muscles, but the effective concentrations are too high to produce clear cardiovascular effects in relation to common biological exposure as was confirmed with the most potent bisphenol AF.

• Klíčová slova
• Bisphenol, Blood pressure, Cardiovascular, Cytotoxicity, Vasorelaxation,
• MeSH
• benzhydrylové sloučeniny * toxicita   metabolismus   MeSH
• kardiovaskulární systém * MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny * MeSH
• bisphenol A MeSH Prohlížeč
• bisphenol AF MeSH Prohlížeč

Exposure to endocrine disruptors such as bisphenols, can lead to and be the explanation for idiopathic infertility. In our study, we assessed the effect of exposure to bisphenol S (BPS) via breast milk on the testicular tissue health of adult male mice. Lactating dams were exposed to BPS through drinking water (0.216 ng g bw/day and 21.6 ng g bw/day) from post-natal day 0-15. Although there was no significant difference in testicular histopathology between the control and experimental groups, we observed an increase in the number of tight and gap junctions in the blood-testis barrier (BTB) of adult mice after lactation BPS exposure. Moreover, there was an increase in oxidative stress markers in adult testicular tissue of mice exposed via breast milk. Our lactation model indicates that breast milk is a route of exposure to an endocrine disruptor that can be responsible for idiopathic male infertility through the damage of the BTB and weakening of oxidative stress resistance in adulthood.

• Klíčová slova
• Bisphenol S, Blood-testis barrier, Idiopathic infertility, Lactation exposure, Oxidative stress, Testicular tissue,
• MeSH
• benzhydrylové sloučeniny toxicita   MeSH
• endokrinní disruptory * toxicita   MeSH
• laktace * MeSH
• myši MeSH
• sulfony toxicita   MeSH
• testis MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• bisphenol S MeSH Prohlížeč
• endokrinní disruptory * MeSH
• sulfony MeSH

Bisphenols, endocrine disrupting chemicals, have frequently been used for producing food packaging materials. The best-known member, bisphenol A (BPA), has been linked to impaired foetal development in animals. Possible negative effects of BPA on human health have resulted in the production of novel, so-called next-generation (NextGen) bisphenols whose effects on humans are much less explored or even missing. This review aimed to summarise and critically assess the main findings and shortages in current bisphenol research in relation to their potential impact on the cardiovascular system in real biological exposure. Because of the common presence of bisphenols in daily use products, humans are clearly exposed to these compounds. Most data are available on BPA, where total serum levels (i.e. included conjugated metabolite) can reach up to ∼430 nM, while free bisphenol levels have been reported up to ∼80 nM. Limited data are available for other bisphenols, but maximal serum levels of bisphenol S have been reported (680 nM). Such levels seem to be negligible, although in vitro studies have showed effects on ion channels, and thyroid, oestrogenic and androgenic receptors in low micromolar concentrations. Ex vivo studies suggest vasodilatory effects of bisphenols. This stays in clear contrast to the elevation of arterial blood pressure documented in vivo and in observatory cross-sectional human studies. Bisphenols are also claimed to have a negative effect on lipidic spectrum and coronary artery disease. Regardless, the reported data are generally inconsistent and unsatisfactory. Hence novel well-designed studies, testing in particular NextGen bisphenols, are needed.

• Klíčová slova
• NextGen bisphenol, atherosclerosis, blood vessels, endocrine-disruptor, heart, vascular,
• MeSH
• benzhydrylové sloučeniny toxicita   MeSH
• endokrinní disruptory * toxicita   MeSH
• fenoly MeSH
• kardiovaskulární systém * MeSH
• průřezové studie MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• bisphenol A MeSH Prohlížeč
• endokrinní disruptory * MeSH
• fenoly MeSH

Male reproductive functions are an important area affecting men´s overall health and well-being. However, during the last years, there has been observed increasing incidence of male reproductive issues. The radical growth has been recorded parallelly with a massive expanse of industrialization and agricultural chemigation. Many groups of experts have begun to identify several potential factors and substances that may have adverse effects on men´s reproductive health. Since then, xenobiotics have become a major concern of many scientific studies. There is evidence that most of them have multigenerational and transgenerational effects on reproductive health, which is a serious problem for our population. Bisphenol A could be considered as one of the most studied endocrine disruptors. Until now, several negative effects of bisphenol A were associated with reduced weight testes, histological alterations, impairment spermatogenesis, and steroidogenesis as well as with testes or prostate cancer. Due to convincing evidence, bisphenol A has been started to replace by its analogues such as bisphenol B, S, F, in order to eliminate and suppress the risk of exposure to bisphenol A. However, it seems that a lack of toxicological analyses allows using of these hazardous substances in daily life. Their harmful effect was confirmed by the animal in vitro and in vivo models, while the epidemiological studies monitoring the impact of bisphenol analogues on men's reproductive health are markedly limited. This review provides information about the effects of bisphenol on reproductive health in men. At the same time, it is focused on physiological aspects of sperm viability, steroid hormone secretion, sperm motility, or testes histology in relation to bisphenols exposure.

• MeSH
• benzhydrylové sloučeniny toxicita   MeSH
• endokrinní disruptory * toxicita   MeSH
• fenoly MeSH
• lidé MeSH
• motilita spermií * MeSH
• spermatogeneze MeSH
• testis MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• bisphenol A MeSH Prohlížeč
• endokrinní disruptory * MeSH
• fenoly MeSH

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.

• Klíčová slova
• Bisphenol, Epigenetics, Oocyte maturation, Spindle formation,
• MeSH
• aparát dělícího vřeténka účinky léků   metabolismus   patologie   MeSH
• benzhydrylové sloučeniny metabolismus   toxicita   MeSH
• epigeneze genetická MeSH
• fenoly metabolismus   toxicita   MeSH
• fertilita účinky léků   MeSH
• hodnocení rizik MeSH
• IVM techniky MeSH
• kojená zvířata MeSH
• laktace metabolismus   MeSH
• matka - expozice noxám MeSH
• mléko metabolismus   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• oocyty účinky léků   metabolismus   patologie   MeSH
• ovariální rezerva účinky léků   MeSH
• ovarium účinky léků   metabolismus   patofyziologie   MeSH
• sulfony metabolismus   toxicita   MeSH
• těhotenství MeSH
• vývojová regulace genové exprese MeSH
• ženská infertilita chemicky indukované   metabolismus   patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• bisphenol F MeSH Prohlížeč
• bisphenol S MeSH Prohlížeč
• fenoly MeSH
• sulfony MeSH

This study summarizes the knowledge about effects of bisphenol A (BPA) and its analogues on reproduction of pigs and some parameters of their offspring during period 2011-2020. Bisphenols are known as one of the most harmful environmental toxicants with endocrine-disrupting properties. One study in the reference period related to male reproductive system. Treatment with an antagonist of G-protein coupled estrogen receptor (GPER) - G15, and bisphenol A and its analogues, tetrabromobisphenol A (TBBPA) and tetrachromobisphenol A (TCBPA) diversely disrupted protein molecules controlling the biogenesis and function of microRNA in Leydig cells. Nine studies examined the effect of BPA, bisphenol S (BPS) or fluorene-9-bisphenol (BHPF) on female reproductive system. From the possible protective effect's point of view seems to be perspective the administration of melatonin in BPA-exposed oocytes. Finally, two studies were found to evaluate the maternal exposure to BPA on offspring's meat quality, muscle metabolism and oxidative stress. Administration of methyl donor improved antioxidant enzymes activity and reduced oxidative stress in piglets.

• Klíčová slova
• Bisphenol, Female, Male, Offspring, Pig, Reproduction,
• MeSH
• benzhydrylové sloučeniny toxicita   MeSH
• endokrinní disruptory * toxicita   MeSH
• fenoly MeSH
• Leydigovy buňky MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• benzhydrylové sloučeniny MeSH
• bisphenol A MeSH Prohlížeč
• endokrinní disruptory * MeSH
• fenoly MeSH
• fluorene-9-bisphenol MeSH Prohlížeč