Bisphenol A Treatment Groups Research Articles

Zebrafish Optomotor Response and Morphology Are Altered by Transient, Developmental Exposure to Bisphenol-A.

Estrogen-specific endocrine disrupting compounds (EDCs) are potent modulators of neural and visual development and common environmental contaminants. Using zebrafish, we examined the long-term impact of abnormal estrogenic signaling by testing the effects of acute, early exposure to bisphenol-A (BPA), a weak estrogen agonist, on later visually guided behaviors. Zebrafish aged 24 h postfertilization (hpf), 72 hpf, and 7 days postfertilization (dpf) were exposed to 0.001 μM or 0.1 μM BPA for 24 h, and then allowed to recover for 1 or 2 weeks. Morphology and optomotor responses (OMRs) were assessed after 1 and 2 weeks of recovery for 24 hpf and 72 hpf exposure groups; 7 dpf exposure groups were additionally assessed immediately after exposure. Increased notochord length was seen in 0.001 μM exposed larvae and decreased in 0.1 μM exposed larvae across all age groups. Positive OMR was significantly increased at 1 and 2 weeks post-exposure in larvae exposed to 0.1 μM BPA when they were 72 hpf or 7 dpf, while positive OMR was increased after 2 weeks of recovery in larvae exposed to 0.001 μM BPA at 72 hpf. A time-delayed increase in eye diameter occurred in both BPA treatment groups at 72 hpf exposure; while a transient increase occurred in 7 dpf larvae exposed to 0.1 μM BPA. Overall, short-term developmental exposure to environmentally relevant BPA levels caused concentration- and age-dependent effects on zebrafish visual anatomy and function.

Effect of Intraperitoneal Injection of Bisphenol-A on Egg Production and Quality Traits in Japanese Quail

This experiment was carried out during winter season 2015, at the Poultry Farm, Department of AnimalProduction, Faculty of Agriculture, Suez Canal University, Ismailia, Egypt. A total of 40 immature female Japanesequail exposed to different levels of Bisphenol-A (BPA) was examined. Three-week-old, quails were individuallyweighted and divided into four groups 10 females' birds in each. The BPA was dissolved in corn oil andintraperitoneally injected weekly in the abdominal cavity of quail for three consecutive weeks (3rd through 5th wksold). The experimental groups were treated by a solution containing (0, 1, 5 and 10 mg BPA/kg BW). During theexperimental period, eggs were collected from each group to estimate egg production and quality traits. At 14 weeksof age, all hens were weighed and then slaughtered in order to collect blood samples to determine serumconcentrations of estradiol-17β hormone. The result showed that exposure of female quail before/at puberty to BPAdelayed initiation of egg production. While the age at first egg in control female was at 47 days of age, consequently,the BPA treated females were slower to reach 50% of their final laying rate. The laying rate of eggs in the control notsignificantly higher than the rate of egg production in all the BPA treatment groups, with the exception of the 10 (mgBPA /kg BW group). BPA treated females showed drastically reduced egg quality compared to controls even with aminimal dose of 1 (mg BPA /kg BW group). Shell thickness and internal quality units were significantly linearlydecreased, but egg shape index was significantly linearly increased with increased BPA dose compared with controlgroup. The lowest ovarian follicle number and oviduct length were detected in 10 (mg BPA/kg BW group), while thehighest values were obtained in 5 (mg BPA/kg BW group). All tested BPA concentrations significantly influencedthe egg production and egg quality in female quail indicating a lowest observed effect concentration of 10 (mgBPA/kg BW). Significant increases of female's body weight and reproductive organ after BPA administration wererecorded, as females produced pre-ovulatory follicles at all tested BPA levels it is presumed that BPA did not affectoogenesis but affect the process of ovulation, the highest values of body weight and reproductive organs of females inthe 5 (mg BPA/kg BW group), estradiol concentration was increased in BPA-treated groups. It could be concludedthat the BPA treatment decreased body weight and delayed puberty and initiation of egg production in female quail.The effect of BPA exposure is proportional to the dose and varies depending on the time of administration.

DNA methylation and copy number variation analyses of human embryonic stem cell-derived neuroprogenitors after low-dose decabromodiphenyl ether and/or bisphenol A exposure.

The polybrominated diphenyl ether flame retardants decabromodiphenyl ether (BDE-209) and bisphenol A (BPA) are environmental contaminants that can cross the placenta and exert toxicity in the developing fetal nervous system. Copy number variants (CNVs) play a role in a number of genetic disorders and may be implicated in BDE-209/BPA teratogenicity. In this study, we found that BDE-209 and/or BPA exposure decreased neural differentiation efficiency of human embryonic stem cells (hESCs), although there was a >90% induction of neuronal progenitor cells (NPCs) from exposed hESCs. However, the mean of CNV numbers in the NPCs with BDE-209 + BPA treatment was significantly higher compared to the other groups, whereas DNA methylation was lower and DNA methyltransferase(DNMT1 and DNMT3A) expression were significantly decreased in all of the BDE-209 and/or BPA treatment groups compared with the control groups. The number of CNVs in chromosomes 3, 4, 11, 22, and X in NPCs with BDE-209 and/or BPA exposure was higher compared to the control group. In addition, CNVs in chromosomes 7, 8, 14, and 16 were stable in hESCs and hESCs-derived NPCs irrespective of BDE-209/BPA exposure, and CNVs in chromosomes 20 q11.21 and 16 p13.11 might be induced by neural differentiation. Thus, BDE-209/BPA exposure emerges as a potential source of CNVs distinct from neural differentiation by itself. BDE-209 and/or BPA exposure may cause genomic instability in cultured stem cells via reduced activity of DNA methyltransferase, suggesting a new mechanism of human embryonic neurodevelopmental toxicity caused by this class of environmental toxins.

A novel approach to assessing bisphenol-A hazards using an in vitro model system.

BackgroundAlthough the toxicological impacts of the xenoestrogen bisphenol-A (BPA) have been studied extensively, but the mechanism of action is poorly understood. Eventually, no standard method exists for evaluating the possible health hazards of BPA exposure. Considering mice spermatozoa as a potential in vitro model, we investigated the effects of BPA exposure (0.0001, 0.01, 1, and 100 μM for 6 h) on spermatozoa and the related mechanisms of action. The same doses were also employed to evaluate protein profiles of spermatozoa as a means to monitor their functional affiliation to diseases.ResultsOur results demonstrated that high concentrations of BPA negatively affect sperm motility, viability, mitochondrial functions, and intracellular ATP levels by activating the mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase-A pathways. Moreover, short-term exposure of spermatozoa to high concentrations of BPA induced differential expressions of 24 proteins. These effects appeared to be caused by protein degradation and phosphorylation in spermatozoa. Proteins differentially expressed in spermatozoa from BPA treatment groups are putatively involved in the pathogenesis of several diseases, mainly cancer, carcinoma, neoplasm, and infertility.ConclusionsBased on these results, we propose that BPA adversely affects sperm function by the activation of several kinase pathways in spermatozoa. In addition, BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa, subsequently involve in the pathogenesis of many diseases. Therefore, we anticipated that current strategy might broadly consider for the health hazards assessment of other toxicological agents.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2979-5) contains supplementary material, which is available to authorized users.

The toxicological effects of bisphenol A and octylphenol on the reproductive system of prepubertal male rats.

The aim of the present study was to assess and compare the individual adverse effects of bisphenol A (BPA) and octylphenol (OP) on the reproductive system of prepubertal male rats. Rats were exposed to BPA and OP at doses of 125 and 250 mg/kg/day, by gavage, for 90 days. At the end of the study, the testes, epididymis, prostate gland, and seminal vesicle were removed and examined histopathologically. Also, 3-β-hydroxysteroid dehydrogenase expressions were analyzed and serum testosterone and luteinizing hormone (LH) levels were measured. Sperm head count of caput epididymis was performed using a hemocytometer. Seminiferous and epididymal round tubules were evaluated for tubule diameter, lumen diameter, and height of tubule epithelium. There were significant increases in relative testes weights in BPA125, OP125, and OP250 groups compared with the control. Atrophic tubules, pyknotic tubules, combined tubules, congestion, vacuolization of Sertoli cell, cell debris in the lumen, tubules without sperm, and degeneration of tubules were noted in the tissue specimens obtained from the treatment groups compared with the control group. Sperm head counts were decreased in all treatment groups except for the low-dose BPA group. Testosterone (T) levels decreased in the BPA and high-dose OP treatment groups. LH levels increased in BPA treatment groups and the low-dose OP treatment group and decreased in the high-dose OP group. Epithelial height of high-dose BPA and OP treatment groups increased compared with the control group. Furthermore tubular height of low-dose BPA and high-dose OP groups increased with respect to control levels. In the OP250 treatment group, thyroxine hormone level was increased compared to other groups. Also, in the OP125 treatment group, triiodothyronine hormone level was increased compared with other groups. The results of this study showed that BPA and OP affect the steroidogenic enzyme expression and T production in Leydig cells. In conclusion, BPA and OP have adverse effects on the male reproductive system of prepubertal rats.

Gestational Exposure to Bisphenol A Affects the Function and Proteome Profile of F1 Spermatozoa in Adult Mice.

Background:Maternal exposure to the endocrine disruptor bisphenol A (BPA) has been linked to offspring reproductive abnormalities. However, exactly how BPA affects offspring fertility remains poorly understood.Objectives:The aim of the present study was to evaluate the effects of gestational BPA exposure on sperm function, fertility, and proteome profile of F1 spermatozoa in adult mice.Methods:Pregnant CD-1 mice (F0) were gavaged with BPA at three different doses (50 μg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on embryonic days 7 to 14. We investigated the function, fertility, and related processes of F1 spermatozoa at postnatal day 120. We also evaluated protein profiles of F1 spermatozoa to monitor their functional affiliation to disease.Results:BPA inhibited sperm count, motility parameters, and intracellular ATP levels in a dose-dependent manner. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelial cells in testis and decreased protein kinase A (PKA) activity and tyrosine phosphorylation in spermatozoa. We also found that BPA compromised average litter size. Proteins differentially expressed in spermatozoa from BPA treatment groups are known to play a critical role in ATP generation, oxidative stress response, fertility, and in the pathogenesis of several diseases.Conclusions:Our study provides mechanistic support for the hypothesis that gestational exposure to BPA alters sperm function and fertility via down-regulation of tyrosine phosphorylation through a PKA-dependent mechanism. In addition, we anticipate that the BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa.Citation:Rahman MS, Kwon WS, Karmakar PC, Yoon SJ, Ryu BY, Pang MG. 2017. Gestational exposure to bisphenol-A affects the function and proteome profile of F1 spermatozoa in adult mice. Environ Health Perspect 125:238–245; http://dx.doi.org/10.1289/EHP378

A unique pattern of bisphenol a effects on nerve growth factor gene expression in embryonic mouse hypothalamic cell line N-44.

We investigated the toxicity of bisphenol A (BPA) by determining the gene expression of nerve growth factor (Ngf in the embryonic mouse cell line mHypoE-N44 derived from the hypothalamus exposed to BPA dose range between 0.02 and 200 μmol L-1 for 3 h. Ngf mRNA levels decreased in a dose-dependent manner, with significant reductions observed in the 2 to 50 μmol L-1 BPA treatment groups compared to controls. However, at 100 to 200 μmol L-1 the NgfmRNA gradually increased and was significantly higher than control, while the expression of the apoptosis-related genes Caspase 3 and transformation-related protein 73 decreased significantly. These results suggest that in an embryonic hypothalamic cell line the higher doses of BPA induce a unique pattern of Ngf gene expression and that BPA has the potential to suppress apoptosis essential for early-stage brain development.

Effects of bisphenol-A on blastocyst development and implantation

To determine the effects of bisphenol-A (BPA) on blastocyst development and implantation. According to completely randomized grouping method, 90 pregnant mice were divided into 100, 300, and 600 mg/(kg·d)BPA groups and control group. BPA-treated pregnant mice were orally administered with BPA at concentrations of 100, 300 and 600 mg/(kg·d) from day 0.5 to day 3.5 of their pregnancy. Blastocyst implantation and development were studied. In the 300 mg/(kg·d) BPA group, the number of implantation sites and implantation rate were significantly decreased. In the 600 mg/(kg·d) group, no implantation sites were observed among pregnant mice and BPA inhibited embryo implantation. Blastocyst development on day 4 was examined, and findings showed that the development rate and total numbers of blastocysts in BPA treatment groups had no significant difference from the control group. However, BPA at 300 and 600 mg/(kg·d) significantly reduced blastocyst hatching rate and dramatically increased the number of blastocyst apoptotic cells when compared with those in the control group. BPA at a high concentration damages the blastocyst development before implantation and inhibits embryo implantation.

Prenatal BPA Exposure Disrupts Ovarian Follicular Wave Dynamics in Adult Sheep.

Concerns regarding the exposure to environmental endocrine disruptors especially those with steroidogenic potential, such as bisphenol A (BPA), are escalating. Developmental exposure to BPA has been found to adversely affect reproductive function in rodents. Translating findings from a multiparous species such as rodents to the human scenario may not be ideal, when the organ system being studied does not follow a similar developmental trajectory. The similarity of neuroendocrine and ovarian changes that occur in sheep relative to human allows a better translational perspective. Prenatal BPA treatment induces reproductive defects in sheep, manifested as LH excess and dampened LH surge. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (B1: 0.05, B2: 0.5, or B3: 5 mg/kg BW/day, s.c., in corn oil) or corn oil (control group [C]). At ~18 months of age, all female offspring (C, B1, B2, B3; n=7, 8, 10, and 6, respectively) were treated with 2 PGF2a injections 11 days apart during their second breeding season to synchronize estrus. Starting on day 10, transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular dynamics (follicles and corpora lutea (CL)). Blood samples were taken daily for 28 days to assess luteal progesterone dynamics during two consecutive cycles. Mantel-Haenszel chi-square test was used to compare follicle size distribution between groups. Follicular size classes were analyzed by a linear mixed effect model. Follicular wave dynamics, CL, and P4 analysis included Fisher's exact test, ANOVA with repeated measures, Mann-Whitney test, and Pearson correlation. Transrectal ultrasonography revealed that none of the three BPA doses had an effect on the number, size, or length of the CLs at the first or second progestogenic cycle studied or the correlation between CL mass and progesterone release. None of the prenatal BPA treatment groups had an effect on the total number or duration of any follicular class (2-3mm, 4-5mm, and = 6mm) or the number of ovulatory follicles relative to the C group. Number of follicular waves (FW) per cycle was restricted to 3 or 4 in C females, while it tended to be more variable in the BPA groups ranging from 2 to 5 FW (P=0.076). However, FW analysis revealed no differences in the mean number, mean day of start, or duration of the FW. Number of small, medium, or large follicles within each FW was numerically higher in C vs. BPA groups in the 1st, 2nd, and 4th FW. Number of medium follicles was higher in C relative to all other BPA groups in the 2nd FW (P<0.05). These findings suggest that the effects of prenatal BPA at the current exposure levels on follicular dynamics are subtle and are evident as variability of FW occurrence and number of emerging follicles per FW. The subtle changes in follicular dynamics coupled with defects in LH release may result in subfertility and early ovarian aging in prenatal BPA-treated females. Supported by NIH ES016541.

Strain specific induction of pyometra and differences in immune responsiveness in mice exposed to 17α-ethinyl estradiol or the endocrine disrupting chemical bisphenol A

Pyometra is an inflammatory disease of the uterus that can be caused by chronic exposure to estrogens. It is unknown whether weakly estrogenic endocrine disruptors can cause pyometra. We investigated whether dietary exposures to the estrogenic endocrine disruptor bisphenol A (BPA) induced pyometra. Pyometra did not occur in CD1 mice exposed to different dietary doses of BPA ranging from 4.1 to >4000μg/kg-d or 17α-ethinyl estradiol (EE; 1.2 to >150μg/kg-d). In the C57BL/6 strain, pyometra occurred in the 15μg/kg-d EE and 33μg/kg-d BPA treatment groups. At the effective concentration of BPA, histological analysis revealed pathological alterations of uterine morphology associated with a >5.3-fold increase in macrophage numbers in non-pyometra uteri of C57BL/6 mice exposed to BPA. These results suggest that BPA enhances immune responsiveness of the uterus and that heightened responsiveness in C57BL/6 females is related to increased susceptibility to pyometra.