Search

Bisphenol A (BPA) is a widely used chemical with a harmful effect on animal and human. The neonatal and juvenile period is a highly risky neurodevelopmental period. This study aimed to determine how male albino rat pups' cerebral cortex was altered by low doses of BPA given to mothers and the role of the oxidative stress. Thirty pregnant rats were randomly split into three equal groups, negative control, and positive control: received 1 cc of corn oil once a day through gastric tube and BPA treated: a dose of 200 µg/kg/day (dissolved in 1 cc corn oil). The male rat pups of each group were sacrificed at 1 week, 3 weeks and 6 weeks. The cerebra were then separated from the brain for histological and biochemical studies. Rats administered BPA had raised levels of lipid peroxidation marker (MDA), lower levels of enzymatic antioxidants (SOD and CAT) with decreased body, cerebral weights, and decreased levels of non-enzymatic antioxidant defense (GSH). Histo-pathologically, shrunken pyramidal cells with congested blood vessels appeared. GFAP displayed increased number of positive immune-reactive astrocytes with high statistically significant increase in the area % in BPA treated group when compared to the control groups, on contrary to MBP. Semi-thin and ultra-thin BPA-sections revealed degenerative changes in myelinated axons with tiny nucleus and broken nuclear membranes. Lysosomes, dilated endoplasmic reticulum cisternae with noticeable increase in unmyelinated nerve fibers were also observed. The structure of the developing cerebral cortex is negatively impacted by BPA due to oxidative stress. • Bisphenol-A groups exhibited a significant elevation of MDA and lowered levels of enzymatic antioxidants (SOD and CAT). • Decreased body, cerebral weights, and (GSH) levels were documented in BPA treated group. • Histo-pathologically, shrunken pyramidal cells with congested blood vessels. • A statistically significant rise in the GFAP immmuno-expression area % in BPA treated group on contrary to MBP was found • Semi-thin and ultra-thin BPA-sections revealed degenerative changes in myelinated axons with tiny nucleus. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is ubiquitous in the environment and its adverse effects on precocious puberty have been reported. But its mechanism is not clear. In the present study, the potential effects of BPA on endocrine functions of hypothalamus, especially in the arcuate (ARC) nucleus and anteroventral periventricular (AVPe) nucleus, were studied from postnatal day 15 (PND15) to PND35 in female Sprague-Dawley (SD) rats. Neonatal rats were exposed to 0.5 mg·kg−1·day−1 BPA or corn oil vehicle from PND1 to PND14 via intramuscular injection. From PND20 to PND 25, BPA caused enrichment of H3K4me2 and H3K4me3 at Kiss1 promoter, concurrent with elevated gene expressions of Kiss1 and GnRH1 in ARC and strikingly increased serum E2 levels in BPA group on PND25. Until PND30, BPA induced obviously overexpression of Kiss1 and GnRH1 in AVPe nucleus. Subsequently, the vagina opening and first ovulation had occurred earlier in rats with BPA exposure in respect to vehicle by PND35. In this study, it is suggested that the effects of BPA on precocious puberty may be due to its action to activate Kiss1 gene in ARC during the juvenile period (from PND20 to PND25) firstly, subsequently to evoke the AVPe neurons, resulting in precocious puberty in the end. • Puberty is initiated by activation of Kiss1 neurons in arcuate nucleus of hypothalamus. • Increased abundance of H3K4me2/3 is relevant to the pubertal activation of Kiss1. • Bisphenol A exposure promotes earlier H3K4me2/3 enrichment at Kiss1 promoter. • Bisphenol A induces precocious puberty by activating Kiss1 in arcuate nucleus in advance. [ABSTRACT FROM AUTHOR]

As the incidence of precocious puberty has risen in recent years and the age at puberty onset is younger, children may be at increased risk for health consequences associated with the early onset of puberty. Bisphenol A (BPA) is recognized as an endocrine disruptor chemical that is reported to induce precocious puberty. The effect of BPA exposure modes, times, and doses (especially low dose) were controversial. In the present study, we evaluated the potential effects of maternal exposure to low-dose BPA on the hypothalamus, particularly on the arcuate (ARC) nucleus and anteroventral periventricular (AVPV) nucleus during peri-puberty in offspring of BPA-treated rats. Pregnant rats were exposed to corn oil vehicle, 0.05 mg·kg−1·day−1 BPA, or 5 mg·kg−1·day−1 from gestation day 1 (GD1) to postnatal day 21 (PND21) by daily gavage. Body weight (BW), vaginal opening (VO), ovarian follicular luteinization, and relevant hormone concentrations were measured; hypothalamic Kiss1 and GnRH1 levels by western immunoblot analysis were also assessed as indices of puberty onset. During or after exposure, low-dose BPA restricted BW after birth (at PND1 and PND5), and subsequently accelerated puberty onset by promoting the expression of prepubertal Kiss1 and GnRH1 in the AVPV nucleus on PND30, leading to advanced VO, an elevation in LH and FSH concentrations (on PND30). We also noted increased BW on PND30 and PND35. Maternal oral exposure to low-dose BPA altered the BW curve during the neonatal and peripubertal periods, and subsequently accelerated puberty onset by promoting prepubertal Kiss1 expression in the AVPV nucleus. • Maternal exposure to low-dose BPA alters the bodyweight curve in female offspring. • Peripubertal hormone levels changed after exposure. • BPA accelerates the development of the ovaries and uteri. • Increased protein levels of Kiss1 and GnRH1 were observed in hypothalamus. [ABSTRACT FROM AUTHOR]

Bisphenols, synthetic organic compounds used in the production of plastics, are an extremely abundant class of Endocrine Disrupting Chemicals, i.e., exogenous chemicals or mixtures of chemicals that can interfere with any aspect of hormone action. Exposure to BPs can lead to a wide range of effects, and it is especially dangerous if it occurs during specific critical periods of life. Focusing on the perinatal exposure to BPA or its largely used substitute BPS, we investigated the effects on anxiety-related behaviors and the serotonergic system, which is highly involved in controlling these behaviors, in adult mice. We treated C57BL/6J dams orally with a dose of 4 μg/kg body weight/day (i.e., EFSA TDI) of BPA or BPS dissolved in corn oil or with vehicle alone, at the onset of mating and continued treatment until the offspring were weaned. Adult offspring of both sexes performed the elevated plus maze and the open field tests. Then, we analyzed the serotonergic system in dorsal (DR) and median (MnR) raphe nuclei by immunohistochemical techniques. Behavioral tests highlighted alterations in BPA- and BPS-treated mice, suggesting different effects of the bisphenols exposure on anxiety-related behavior in males (anxiolytic) and females (anxiogenic). The analysis of the serotonergic system highlighted a sex dimorphism in the DR only, with control females showing higher values of serotonin immunoreactivity (5-HT-ir) than control males. BPA-treated males displayed a significant increase of 5-HT-ir in all analyzed nuclei, whereas BPS-treated males showed an increase in ventral DR only. In females, both bisphenols-treated groups showed a significant increase of 5-HT-ir in dorsal DR compared to the controls, and BPA-treated females also showed a significant increase in MnR.These results provide evidence that exposure during the early phases of life to BPA or BPS alters anxiety and the raphe serotonergic neurons in a sex-dependent manner. [Display omitted] • Exposure to low-dose bisphenol A or S during the perinatal period represents a risk to the developing organism. • Anxiety-related behaviors are altered in bisphenol A or S-exposed mice. • Serotonergic system within dorsal and median raphe nuclei is altered in bisphenol A or S exposed mice. • Perinatal exposure to bisphenol A or S affected differentially the two sexes. • New and more stringent regulations on the use of BPA and its analogue BPS are needed. [ABSTRACT FROM AUTHOR]

This study was performed to examine whether bisphenol (BP) A analogues, BPE and BPS, negatively impacts reproductive functions using mice as a model. CD-1 mice were exposed to control treatment (corn oil), BPA, BPE and BPS (50 μg/kg or 10 mg/kg) from birth to postnatal day (PND) 60 by s.c. injection every three days. Sperm counts or motility was significantly reduced by BPA, BPE or BPS exposure on PND 60 or PND 90. Exposure of BPA, BPE and BPS disrupted the progression of germ cell development, as morphometric analyses exhibited an abnormal distribution of the stages of spermatogenesis. In females, postnatal BPA and BPE exposure accelerated the onset of puberty, and increased body weight after parturition. Furthermore, postnatal exposure of BPA, BPE and/or BPS increased steroid hormone levels in serum. These results suggest that BPA analogues (BPS and BPE) affects male and female reproductive functions. [ABSTRACT FROM AUTHOR]

Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (< 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis). [Display omitted] • Oxidative stress and inflammation – the most important mechanisms. • Changes in rat liver – most prominent/present only in the MIX group. • Redox status and bioelements changes – most prominent/present only in the MIX group. • Zebrafish: DBP in binary mixtures – lethal outcome at two highest concentrations. • Zebrafish: hepatotoxicity of DEHP/DBP/BPA mixture dictated by BPA. [ABSTRACT FROM AUTHOR]

Abstract: Previous work has shown that exposure to bisphenol A (BPA) can affect anxiety behavior. However, no studies have examined whether administration of this endocrine disruptor during the perinatal period has the potential to induce alterations in cognitive behavior in both adult males and females as assessed in an appetitive task. The goal of the current study was to determine whether exposure to different doses of BPA during early development alters performance on the 17-arm radial maze in adulthood in Long–Evans rats. Oral administration of corn oil (vehicle), 4μg/kg, 40μg/kg, or 400μg/kg BPA to the dams occurred daily throughout pregnancy, and the pups received direct oral administration of BPA between postnatal days 1–9. Blood was collected from offspring at weaning age to determine levels of several hormones (thyroxine, thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone). One male and one female from each litter were evaluated on the 17-arm radial maze, a working/reference memory task, in adulthood. Results indicated that after exposure to BPA at both 4 and 400μg/kg/day, rats of both sexes had decreased levels of FSH at weaning. There were no significant effects of BPA on performance on the radial arm maze in males or females. In conclusion, exposure to BPA during early development had modest effects on circulating hormones but did not affect performance on a spatial learning and memory task. [Copyright &y& Elsevier]

Abstract: This study examines the effects of neonatal exposure to the endocrine disruptor bisphenol A (BPA) on the hypothalamic circuitry controlling the female sexual behaviors of adult rats. From postnatal day 1 (PND1) to PND7, pups were injected with corn oil (control) or BPA (BPA20: 20mg/kg-d; BPA.05: 0.05mg/kg-d) and at PND85 the rats were bilaterally ovariectomized (OVX). At PND100, OVX-rats received estradiol alone or estradiol and progesterone to evaluate estrogen-dependent gene expression in the hypothalamus and sexual behavior. In BPA-exposed females, estrogen receptor alpha (ERα) expression was down-regulated in both the medial preoptic (MPN) and ventromedial nucleus (VMHvl), while repressor of estrogen receptor activity (REA) expression was up-regulated in the VMHvl. Interestingly, BPA-exposed females displayed significantly lower levels of proceptive behavior. Our results show that BPA permanently alters the hypothalamic estrogen-dependent mechanisms that govern sexual behavior in the adult female rat. [Copyright &y& Elsevier]

The aim of this study was to explore the mechanisms of bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) mixture-induced asthma development and test probiotic as a potential positive intervention. Comparative Toxicogenomics Database (CTD) and ToppGene Suite were used as the main tools for in silico analysis. In vivo 28-day experiment was conducted on rats - seven groups (n = 6): (1) Control: corn oil, (2) P: probiotic (8.78 * 108 CFU/kg/day); (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day; (6) MIX: DEHP + DBP + BPA; (7) MIX + P. Lungs, thymus and kidneys were extracted and prepared for redox status and essential metals analysis. By conducting additional in vitro experiment, probiotic phthalate and BPA binding ability was explored. There were 24 DEHP, DBP and BPA asthma-related genes, indicating the three most probable mechanisms - apoptosis, inflammation and oxidative stress. In vivo experiment confirmed that significant changes in redox status/essential metal parameters were either prominent, or only present in the MIX group, indicating possible additive effects. In vitro experiment confirmed the ability of the multy-strain probiotic to bind DEHP/DBP/BPA mixture, while probiotic administration ameliorated mixture-induced changes in rat tissue. [Display omitted] • MIX (DEHP + DBP + BPA): 24 mutual genes connected with asthma development. • Apoptosis, inflammation and oxidative stress – the most probable mechanisms. • Redox status and bioelements changes – most prominent/present only in the MIX group. • Multi-strain probiotic bound 29.25, 29.04 and 41.75% for DEHP, DBP and BPA. • Probiotic mitigated MIX-induced changes in rat lung, thymus and kidney tissue. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that developmental exposure to bisphenol A (BPA)—a synthetic endocrine disruptor—causes atypical reproductive phenotypes that may persist for generations. However, the precise mechanism(s) by which BPA causes these adverse consequences is unclear. Here, pregnant female mice were orally exposed to 50 μg, 5 mg, and 50 mg BPA/kg body weight (bw)/day from 7 to 14 days of gestation. Corn oil treatments were used as control. The first filial generation (F1) and F2 males were used to generate F3 by mating them with unexposed females. High BPA doses impaired F1 and/or F1–F2 (multigenerational effect) male reproduction (i.e., disrupted testicular germ cell organization and spermatogenesis, altered sperm biochemical properties, and decreased sperm count, motility, and fertility) but not that of F3 males (transgenerational effect). Moreover, the observed multigenerational transmission of the abnormal reproductive traits was associated with alterations in the sperm DNA methylation patterns of specific male generations, with substantial proteomic changes in F1–F3 at the highest BPA dose. Given that the proteins related to male fertility and epigenetic modification are highly conserved among vertebrates, our findings may shed light on how exposure to environmental factors during pregnancy affects fertility in future generations in both humans and the other animals. [Display omitted] • BPA affects germ cell organization, spermatogenesis, sperm function, and fertility. • BPA significantly impaired sperm function/male fertility in F1 and/or F1–F2 males. • BPA effects linked to DNA methylation and proteome changes in male germ cells. • Levels of BPA exposure need to be redefined that are currently thought to be nontoxic. [ABSTRACT FROM AUTHOR]

Linkage between bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA) co-exposure and type 2 diabetes mellitus (T2DM), as well as ability of multi-strained probiotic to reduce DEHP, DBP and BPA mixture-induced oxidative damage in rat pancreas were investigated. The Comparative Toxicogenomics Database, Cytoscape software and ToppGene Suite were used for data-mining. Animals were sorted into seven groups (n = 6): (1) Control group: corn oil, (2) P: probiotic: Saccharomyces boulardii + Lactobacillus rhamnosus + Lactobacillus plantarum LP 6595 + Lactobacillus plantarum HEAL9; (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day, and (6) MIX: 50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA; (7) MIX + P. Rats were sacrificed after 28 days of oral exposure. In silico investigation highlighted 44 DEHP, DBP and BPA mutual genes linked to the T2DM, while apoptosis and oxidative stress were highlighted as the main mechanisms of DEHP, DBP and BPA mixture-linked T2DM. In vivo experiment confirmed the presence of significant changes in redox status parameters (TOS, SOD and SH groups) only in the MIX group, indicating possible additive effects, while probiotic ameliorated mixture-induced redox status changes in rat pancreatic tissue. [Display omitted] • MIX (DEHP, DBP and BPA): 44 mutual genes linked to T2DM. • Apoptosis and oxidative stress – the most probable mechanisms of MIX-linked T2DM. • Significant redox status parameters changes (TOS, SOD and SH) only in the MIX group. • Polybiotic ameliorated MIX-induced redox status changes in rat pancreatic tissue. [ABSTRACT FROM AUTHOR]

Phthalates and bisphenol A, to which people are mainly exposed through food, interfere with the body's endocrine system, along with various other toxic effects. Literature data suggest that probiotic cultures might be able to decrease the adverse effects of toxic substances by various mechanisms. The aim of this study was to investigate if treatment with multi-strained probiotic could reduce the toxicity of phthalates and bisphenol A mixture in Wistar rats. Animals were divided into four experimental groups (n = 6): (1) Control (corn oil); (2) P (probiotic (8.78 * 108 CFU/kg/day): Saccharomyces boulardii + Lactobacillus rhamnosus + Lactobacillus planarum LP 6595+ Lactobacillus planarum HEAL9); (3) MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA); (4) MIX + P. Animals were euthanized after 28 days of daily oral gavage treatment; blood and organs were collected for further analysis. Probiotic reduced systemic inflammation and had protective effects on liver, kidneys, spleen, lipid status and serum glucose level. It almost completely annulled the changes in biochemical, hematological and hormonal parameters and mitigated changes in relative liver size, food consumption and organ histology. These results suggest considering multi-strained probiotics as a dietary therapeutic strategy against toxicity of the investigated mixture. Image 1 • Probiotic reduced phthalates and bisphenol A mixture-induced organ toxicity. • The probiotic treatment attenuated mixture-induced systemic inflammation. • Probiotic annulled changes in biochemical, hematological and hormonal parameters. • Probiotic mitigated changes in liver weight, food consumption and organ histology. • Multi-strained probiotic – potential strategy against mixture toxicity. [ABSTRACT FROM AUTHOR]