scholarly journals Unexpected Interacting Effects of Physical (Radiation) and Chemical (Bisphenol A) Treatments on Male Reproductive Functions in Mice

2021 ◽  
Vol 22 (21) ◽  
pp. 11808
Author(s):  
Margaux Wieckowski ◽  
Stéphanie Ranga ◽  
Delphine Moison ◽  
Sébastien Messiaen ◽  
Sonia Abdallah ◽  
...  

For decades, numerous chemical pollutants have been described to interfere with endogenous hormone metabolism/signaling altering reproductive functions. Among these endocrine disrupting substances, Bisphenol A (BPA), a widely used compound, is known to negatively impact germ and somatic cells in the testis. Physical agents, such as ionizing radiation, were also described to perturb spermatogenesis. Despite the fact that we are constantly exposed to numerous environmental chemical and physical compounds, very few studies explore the impact of combined exposure to chemical and physical pollutants on reproductive health. The aim of this study was to describe the impact of fetal co-exposure to BPA and IR on testicular function in mice. We exposed pregnant mice to 10 µM BPA (corresponding to 0.5 mg/kg/day) in drinking water from 10.5 dpc until birth, and we irradiated mice with 0.2 Gy (γ-ray, RAD) at 12.5 days post-conception. Co-exposure to BPA and γ-ray induces DNA damage in fetal germ cells in an additive manner, leading to a long-lasting decrease in germ cell abundance. We also observed significant alteration of adult steroidogenesis by RAD exposure independently of the BPA exposure. This is illustrated by the downregulation of steroidogenic genes and the decrease of the number of adult Leydig cells. As a consequence, courtship behavior is modified, and male ultrasonic vocalizations associated with courtship decreased. In conclusion, this study provides evidence for the importance of broadening the concept of endocrine disruptors to include physical agents, leading to a reevaluation of risk management and regulatory decisions.

2000 ◽  
Vol 14 (3) ◽  
pp. 421-428 ◽  
Author(s):  
Hisashi Masuyama ◽  
Yuji Hiramatsu ◽  
Mamoru Kunitomi ◽  
Takafumi Kudo ◽  
Paul N. MacDonald

Abstract Recently, Pregnane X receptor (PXR), a new member of the nuclear receptor superfamily, was shown to mediate the effects of several steroid hormones, such as progesterone, glucocorticoid, pregnenolone, and xenobiotics on cytochrome P450 3A genes (CYP3A) through the specific DNA sequence for CYP3A, suggesting that PXR may play a role in steroid hormone metabolism. In this paper, we demonstrated that phthalic acid and nonylphenol, endocrine-disrupting chemicals (EDCs), stimulated PXR-mediated transcription at concentrations comparable to those at which they activate estrogen receptor-mediated transcription using a transient reporter gene expression assay in COS-7 cells. However, bisphenol A, another EDC, had no effect on PXR-mediated transcription, although this chemical significantly enhanced ER-mediated transcription. In the yeast two-hybrid protein interaction assay, PXR interacted with two nuclear receptor coactivator proteins, steroid hormone receptor coactivator-1 and receptor interacting protein 140, in the presence of phthalic acid or nonylphenol. Thus, EDC-occupied PXR may regulate its specific gene expression through the receptor-coactivator interaction. In contrast, these EDCs had no effect on the interaction between PXR and suppressor for gal 1, a component of proteasome. Finally, the expression of CYP3A1 mRNA in the liver of rats exposed to phthalic acid or nonylphenol markedly increased compared with that in rats treated with estradiol, bisphenol A, or ethanol as assessed by competitive RT-PCR. These data suggest that EDCs may affect endocrine functions by altering steroid hormone metabolism through PXR.


Author(s):  
Aylin Jamali Khaghani ◽  
Parisa Farrokh ◽  
Saeed Zavareh

Background: Bisphenol A (BPA), a synthetic endocrine-disrupting chemical, is a reproductive toxicant. Granulosa cells have significant roles in follicle development, and KIT ligand (KITL) and Anti-Müllerian hormone (AMH) are essential biomolecules produced by them during folliculogenesis. Objective: Due to the widespread use of BPA and its potential epigenetic effects, this study examined the impact of BPA on promoter methylation of amh and kitl genes in mouse granulosa cells. Materials and Methods: Preantral follicles were isolated from ovaries of immature mice and cultured for eight days. Then, follicles were treated with 50 and 100 μM of BPA, and 0.01% (v/v) ethanol for 24 and 72 hr. Growth and degeneration of follicles and antrum formation were analyzed. The granulosa cells were isolated mechanically, and their extracted DNA was treated with sodium bisulfite. The promoter regions of the amh and kitl were analyzed with PCR and sequencing. Results: BPA did not change follicle survival and antrum formation significantly (p = 0.41). However, the culture in the presence of 100 μM BPA had an inhibitory effect on growth. Before BPA treatment, the CpG of the kitl and amh promoters were unmethylated and partially methylated, respectively. While the percent of 5mC in the amh promoter reduced at 100 μM of BPA, it did not alter the kitl promoter methylation. Conclusion: BPA at higher concentrations has an inhibitory effect on follicle growth. Moreover, it seems that the epigenetic impact of BPA restricts to the demethylation of CpG sites. Key words: Bisphenol A, DNA methylation, Granulosa cells.


2017 ◽  
Author(s):  
Robin B. Gear ◽  
Scott M. Belcher

ABSTRACTThe endocrine disruptor bisphenol A (BPA) and the pharmaceutical 17α-ethinyl estradiol (EE) are synthetic chemicals with estrogen-like activities. Despite ubiquitous human exposure to BPA, and the wide-spread clinical use of EE as oral contraceptive adjuvant, the impact of these estrogenic endocrine disrupting chemicals (EDCs) on the immune system is unclear. Here we report results of in vivo dose response studies that analyzed the histology and microstructural changes in the spleen of adult male and female CD-1 mice exposed to 4 to 40,000 μg/kg/day BPA or 0.02 to 2 μg/kg/day EE from conception until 12-14 weeks of age. Results of that analysis indicate that both BPA and EE have dose- and sex-specific impacts on the cellular and microanatomical structures of the spleens that reveal minor alterations in immunomodulatory and hematopoietic functions. These findings support previous studies demonstrating the murine immune system as a sensitive target for estrogens, and that oral exposures to BPA and EE can have estrogen-like immunomodulatory affects in both sexes.


Author(s):  
Rebecca Whitehead ◽  
Haiyan Guan ◽  
Edith Arany ◽  
Maria Cernea ◽  
Kaiping Yang

AbstractExposure to bisphenol A (BPA), an endocrine disrupting chemical, during gestation is associated with a variety of metabolic dysfunctions in adulthood, including hyperinsulinemia, glucose intolerance and insulin resistance. These modifications in glucose homeostasis largely stem from alterations in pancreatic function. However, the effects of BPA on the fetal pancreas have never been explored. The present study addressed this important question by examining the effects of prenatal BPA exposure on the mouse fetal pancreatic development.Pregnant mice were fed a BPA diet (25 mg BPA/kg diet) from embryonic day 7.5 (E7.5) to E18.5. At E18.5, fetal pancreata were collected and analyzed for morphological changes in the endocrine pancreas such as islet size, number and β and α cell distribution.We showed that BPA exposed fetal pancreata had a greater number of islet-cell clusters (ICCs; <300 μmConsidering that ICCs represent the initial stages of islet development in the fetal pancreas, our findings suggest that BPA promotes islet differentiation or delays the conversion of ICCs into mature islets. Moreover, the increase in glucagon expression suggests a potential alteration in the α:β-cell ratio in islets, which may have significant implications for the fetal pancreas both structurally and functionally. This study provides novel insight into the effects of BPA exposure on the fetal pancreata, indicating alterations in glucagon expression in islets and ICCs.


Author(s):  
Enoch Appiah Adu-Gyamfi ◽  
Cheryl S Rosenfeld ◽  
Geetu Tuteja

Abstract Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) that is used in a wide-variety of plastic and common house-hold items. Therefore, there is potential continual exposure to this compound. BPA exposure has been linked to certain placenta-associated obstetric complications such as preeclampsia, fetal growth restriction, miscarriage, and preterm birth. However, how BPA exposure results in these disorders remains uncertain. Hence, we have herein summarized the reported impact of BPA on the morphology and metabolic state of the placenta and have proposed mechanisms by which BPA affects placentation, potentially leading to obstetric complications. Current findings suggest that BPA induces pathological changes in the placenta and disrupts its metabolic activities. Based on exposure concentrations, BPA can elicit apoptotic or anti-apoptotic signals in the trophoblasts; and can exaggerate trophoblast fusion while inhibiting trophoblast migration and invasion to affect pregnancy. Accordingly, the usage of BPA products by pregnant women should be minimized and less harmful alternative chemicals should be explored and employed where possible.


2020 ◽  
Vol 89 (3) ◽  
pp. e441
Author(s):  
Justyna Milczarek-Banach ◽  
Piotr Miśkiewicz

Bisphenols (BPs) are common plastic additives widely used in industry, hence, human exposure to BPs is inevitable. The best known BP is bisphenol A (BPA), the production of which and its analogues has been increasing worldwide. This chemical is classified as an endocrine-disrupting chemical, inferring with hormonal homeostasis. Indeed, BPA is associated with the development of oestrogen-dependent neoplasms, infertility, metabolic disorders and neurobehavioral disturbances. However, there is a lack of evidence regarding the impact of BPA and its analogues on the thyroid, with most studies mainly performed on animals or in vitro. This review aims to summarise the knowledge regarding the relationship between BPA and its analogues on the thyroid gland.


2005 ◽  
Vol 40 (4) ◽  
pp. 484-490 ◽  
Author(s):  
Keun J. Choi ◽  
Sang G. Kim ◽  
Chang W. Kim ◽  
Seung H. Kim

Abstract This study examined the effect of polyphosphate on removal of endocrine-disrupting chemicals (EDCs) such as nonylphenol and bisphenol-A by activated carbons. It was found that polyphosphate aided in the removal of nonylphenol and bisphenol- A. Polyphosphate reacted with nonylphenol, likely through dipole-dipole interaction, which then improved the nonylphenol removal. Calcium interfered with this reaction by causing competition. It was found that polyphosphate could accumulate on carbon while treating a river. The accumulated polyphosphate then aided nonylphenol removal. The extent of accumulation was dependent on the type of carbon. The accumulation occurred more extensively with the wood-based used carbon than with the coal-based used carbon due to the surface charge of the carbon. The negatively charged wood-based carbon attracted the positively charged calcium-polyphosphate complex more strongly than the uncharged coal-based carbon. The polyphosphate-coated activated carbon was also effective in nonylphenol removal. The effect was different depending on the type of carbon. Polyphosphate readily attached onto the wood-based carbon due to its high affinity for polyphosphate. The attached polyphosphate then improved the nonylphenol removal. However, the coating failed to attach polyphosphate onto the coal-based carbon. The nonylphenol removal performance of the coal-based carbon remained unchanged after the polyphosphate coating.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Diksha Sirohi ◽  
Ruqaiya Al Ramadhani ◽  
Luke D. Knibbs

AbstractPurposeEndocrine-related diseases and disorders are on the rise globally. Synthetically produced environmental chemicals (endocrine-disrupting chemicals (EDCs)) mimic hormones like oestrogen and alter signalling pathways. Endometriosis is an oestrogen-dependent condition, affecting 10–15% of women of the reproductive age, and has substantial impacts on the quality of life. The aetiology of endometriosis is believed to be multifactorial, ranging from genetic causes to immunologic dysfunction due to environmental exposure to EDCs. Hence, we undertook a systematic review and investigated the epidemiological evidence for an association between EDCs and the development of endometriosis. We also aimed to assess studies on the relationship between body concentration of EDCs and the severity of endometriosis.MethodFollowing PRISMA guidelines, a structured search of PubMed, Embase and Scopus was conducted (to July 2018). The included studies analysed the association between one or more EDCs and the prevalence of endometriosis. The types of EDCs, association and outcome, participant characteristics and confounding variables were extracted and analysed. Quality assessment was performed using standard criteria.ResultsIn total, 29 studies were included. Phthalate esters were positively associated with the prevalence of endometriosis. The majority (71%) of studies revealed a significant association between bisphenol A, organochlorinated environmental pollutants (dioxins, dioxin-like compounds, organochlorinated pesticides, polychlorinated biphenyls) and the prevalence of endometriosis. A positive association between copper, chromium and prevalence of endometriosis was demonstrated in one study only. Cadmium, lead and mercury were not associated with the prevalence of endometriosis. There were conflicting results for the association between nickel and endometriosis. The relationship of EDCs and severity of endometriosis was not established in the studies.ConclusionWe found some evidence to suggest an association between phthalate esters, bisphenol A, organochlorinated environmental pollutants and the prevalence of endometriosis. Disentangling these exposures from various other factors that affect endometriosis is complex, but an important topic for further research.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
E Haverinen ◽  
R Lange ◽  
H Tolonen

Abstract Increasing prevalence of metabolic syndrome (MetS) is causing significant health burden among the European population. Current knowledge supports the notion that endocrine disrupting chemicals (EDCs) interfere with human metabolism and hormonal balance, contributing to the conventionally recognized life-style related risk factors for MetS. In relation to the Human biomonitoring initiative (HBM4EU) five priority substances (Bisphenol A, Per- and polyfluoroalkyl substances (PFASs), Phthalates, Cadmium and Arsenic) and their association with adverse metabolic health effects were examined. A methodological framework for scoping reviews was followed to increase consistency and transparency throughout the process. A literature review was conducted to identify epidemiological studies focusing on the association between MetS or its individual components and the five HBM4EU priority substances. Human biomonitoring studies have been able to present evidence supporting EDC exposure and development of individual MetS components; however the strength of the association varies between the components and EDCs. Most of the identified literature examined Bisphenol A and Phthalate exposure, usually targeting obesity, anthropometrics or glucose metabolism. Evidence suggests a positive association between Bisphenol A and Phthalate exposure and obesity-related components. The substance group of PFASs indicated weakest association, as the results were inconsistent and were suggestive only for a positive association with development of dyslipidaemia. Current evidence on metabolic disturbances and EDCs are inconclusive and fragmented, hence establishing harmonized and standardized human biomonitoring procedures among the European population are needed. Rigorous and ongoing human biomonitoring in combination with health monitoring could provide comprehensive information on EDC exposure and association of metabolic disturbances. Key messages EDC exposure is ubiquitous within European population, hence more human biomonitoring in combination with health surveys is needed to strengthen knowledge on human’s metabolic health. MetS is an increasing global health concern, which requires novel approaches to tackle the challenge.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 780
Author(s):  
Krystyna Makowska ◽  
Slawomir Gonkowski

Bisphenol A (BPA) contained in plastics used in the production of various everyday objects may leach from these items and contaminate food, water and air. As an endocrine disruptor, BPA negatively affects many internal organs and systems. Exposure to BPA also contributes to heart and cardiovascular system dysfunction, but many aspects connected with this activity remain unknown. Therefore, this study aimed to investigate the impact of BPA in a dose of 0.05 mg/kg body weight/day (in many countries such a dose is regarded as a tolerable daily intake–TDI dose of BPA–completely safe for living organisms) on the neurochemical characterization of nerves located in the heart wall using the immunofluorescence technique. The obtained results indicate that BPA (even in such a relatively low dose) increases the number of nerves immunoreactive to neuropeptide Y, substance P and tyrosine hydroxylase (used here as a marker of sympathetic innervation). However, BPA did not change the number of nerves immunoreactive to vesicular acetylcholine transporter (used here as a marker of cholinergic structures). These observations suggest that changes in the heart innervation may be at the root of BPA-induced circulatory disturbances, as well as arrhythmogenic and/or proinflammatory effects of this endocrine disruptor. Moreover, changes in the neurochemical characterization of nerves in the heart wall may be the first sign of exposure to BPA.


Sign in / Sign up

Export Citation Format

Share Document