Endocrine disrupting chemicals and reproductive disorders in women, men, and animal models.
Advances in pharmacology (San Diego, Calif.)
This chapter covers the known effects of endocrine disrupting chemicals (EDCs) on reproductive disorders. The EDCs represented are highly studied, including plasticizers (bisphenols and phthalates), chemicals in personal care products (parabens), persistent environmental contaminants (polychlorinated biphenyls), and chemicals in pesticides or herbicides. Both female and male reproductive disorders are reviewed in the chapter. Female disorders include infertility/subfertility, irregular reproductive cycles, early menopause, premature ovarian insufficiency, polycystic ovarian syndrome, endometriosis, and uterine fibroids. Male disorders include infertility/subfertility, cryptorchidism, and hypospadias. Findings from both human and animal studies are represented.
10.1016/bs.apha.2021.03.008
Distribution and potential risk factors of bisphenol a in serum and urine among Chinese from 2004 to 2019.
Frontiers in public health
Background:Bisphenol A (BPA) is an oil-derived, large-market volume chemical with endocrine disrupting properties and reproductive toxicity. Moreover, BPA is frequently used in food contact materials, has been extensively researched recently, and widespread exposure in the general population has been reported worldwide. However, national information on BPA levels in general Chinese people is lacking. Methods:This study collected and analyzed 145 (104 in urine and 41 in serum) research articles published between 2004 and 2021 to reflect the BPA internal exposure levels in Chinese populations. The Monte Carlo simulation method is employed to analyze and estimate the data in order to rectify the deviation caused by a skewed distribution. Results:Data on BPA concentrations in urine and serum were collected from 2006 to 2019 and 2004 to 2019, respectively. Urinary BPA concentrations did not vary significantly until 2017, with the highest concentration occurring from 2018 to 2019 (2.90 ng/mL). The serum BPA concentration decreased to the nadir of 1.07 ng/mL in 2011 and gradually increased to 2.54 ng/mL. Nationally, 18 provinces were studied, with Guangdong (3.50 ng/mL), Zhejiang (2.57 ng/mL), and Fujian (2.15 ng/mL) having the highest urine BPA levels. Serum BPA was investigated in 15 provinces; Jiangsu (9.14 ng/mL) and Shandong (5.80 ng/mL) were relatively high. The results also indicated that males' urine and serum BPA levels were higher than females, while the BPA levels in children were also higher than in adults ( < 0.001). Furthermore, the volume of garbage disposal ( = 0.39, < 0.05), household sewage ( = 0.34, < 0.05), and waste incineration content ( = 0.35, < 0.05) exhibited a strong positive connection with urine BPA levels in Chinese individuals. Conclusion:Despite using a data consolidation approach, our study found that the Chinese population was exposed to significant amounts of BPA, and males having a higher level than females. Besides, the levels of BPA exposure are influenced by the volume of garbage disposal, household sewage, and waste incineration content.
10.3389/fpubh.2024.1196248
Placenta expressing the greatest quantity of bisphenol A receptor ERR{gamma} among the human reproductive tissues: Predominant expression of type-1 ERRgamma isoform.
Takeda Yukimasa,Liu Xiaohui,Sumiyoshi Miho,Matsushima Ayami,Shimohigashi Miki,Shimohigashi Yasuyuki
Journal of biochemistry
Estrogen-related receptor gamma (ERRgamma), one of the 48 human nuclear receptors, has a fully active conformation with no ligand. We recently demonstrated that ERRgamma binds strongly bisphenol A (BPA), one of the nastiest endocrine disruptors, and thus retaining ERRgamma's high basal constitutive activity. A report that BPA accumulates in the human maternal-fetal placental unit has led us to hypothesize that a large amount of ERRgamma might exist in the human placenta. Here we report evidence that placenta indeed expresses ERRgamma exceptionally strongly. We first ascertained the presence of nine different ERRgamma mRNA variants and the resulting three ERRgamma protein isoforms. By real-time PCR, we estimated the relative amount of ERRgamma mRNA using total RNA extracts from human reproductive tissues. Placenta was found to express ERRgamma extremely highly. Among the three ERRgamma protein isoforms, placenta exclusively expresses the type-1 isoform, which possesses additional 23-mer amino-acid residues at the N-terminus of the ordinary ERRgamma. This N-terminal elongation was found to elevate by approximately 50% the basal constitutive activity of ERRgamma, as evidenced in the luciferase reporter gene assay. The present results suggest that BPA accumulates in the placenta by binding to ERRgamma.
10.1093/jb/mvp049
Bisphenol A promotes autophagy in ovarian granulosa cells by inducing AMPK/mTOR/ULK1 signalling pathway.
Environment international
BACKGROUND:Bisphenol A (BPA) is a widespread endocrine-disrupting chemical with estrogen like effects, which could interfere with the human reproductive system by disrupting the normal function of granulosa cells (GCs) leading to abnormal ovarian function. However, the mechanism of its toxicity on human GCs has not been clearly described thus far. METHODS:106 normogonadotropic infertile women undergoing their first in-vitro fertilization-embryo transfer (IVF-ET) cycle were recruited. Urinary BPA level and the early outcomes of IVF-ET were analysed. Patients were divided to low and high BPA exposure groups using the median urinary BPA concentration as the cut-off value. In-vivo and in-vitro studies were conducted using mice and human granulosa cell line (KGN cells). Female Kunming mice approximately 6-8 weeks of age were poisoned with BPA at different dosages (1, 10 or 100 μg/kg) by oral gavage once daily for 2 weeks, while KGN cells were exposed to BPA at the concentration of 1, 10 or 100 nM for 24 h, 48 h or 72 h. BPA-induced ovarian morphologic changes were analysed by histopathology investigation. Cell viability and apoptosis were evaluated using CCK-8, TUNEL and flowcytometric, respectively. Hormone levels were determined using ELISA and the molecular mechanism studies were conducted using immunofluorescence, RT-PCR and western blots. RESULTS:The oocyte retrieval rate, maturation rate and embryo implantation rate significantly decreased with the higher level of urinary BPA concentration. Peak E2 level was lower in high BPA group, but no statistical significance could be observed. In BPA treated mice, cystic dilation of the follicles with a decreased number of GCs could be observed histopathologically. Decreased E2, P4 and AMH level and GCs autophagy could be detected both in-vivo and in-vitro with the activation of AMPK/mTOR/ULK1 signalling pathway. As being confirmed in KGN cells, phosphorylated AMPK and ULK1 increased while phosphorylated mTOR decreased, and by inhibition autophagy using knockdown of AMPK or 3-MA, adverse effects of BPA exposure in-vitro could be reversed. CONCLUSION:BPA exposure might abnormally influence human ovarian functions leading to abnormal folliculogenesis by activation of autophagy in GCs through AMPK/mTOR/ULK1 pathway.
10.1016/j.envint.2020.106298
Influence of Tetrabromobisphenol A, with or without Concurrent Triclosan, upon Bisphenol A and Estradiol Concentrations in Mice.
Pollock Tyler,Mantella Leanna,Reali Vanessa,deCatanzaro Denys
Environmental health perspectives
BACKGROUND:Humans are commonly exposed to multiple environmental chemicals, including tetrabromobisphenol A (TBBPA; a flame retardant), triclosan (an antimicrobial agent), and bisphenol A (BPA; polycarbonate plastics). These chemicals are readily absorbed and may interact with each other. OBJECTIVES:We sought to determine whether TBBPA, given alone or in combination with triclosan, can modulate the concentrations of BPA and 17β-estradiol (E2). METHODS:Female and male CF-1 mice were each given a subcutaneous injection of 0-27mg TBBPA, with or without concurrent 0.33mg triclosan, followed by dietary administration of 50μg/kg body weight C-BPA. Radioactivity was measured in blood serum and tissues through liquid scintillation counting. In subsequent experiments, female and male CF-1 mice were each given a subcutaneous injection of 0 or 1mg TBBPA and E2 was measured in urine 2-12 h after injection. RESULTS:Doses as low as 1mg TBBPA significantly elevated C-BPA concentrations in the uterus and ovaries of females; in the testes, epididymides, vesicular-coagulating glands, and preputial glands of males; and in blood serum, heart, lungs, and kidneys of both sexes; urinary E2 concentrations were also elevated. Lower doses of TBBPA or triclosan that had no effects on their own elevated C-BPA concentrations when the two substances were given concurrently. CONCLUSION:These data indicate that TBBPA, triclosan, and BPA interact , consistent with evidence that TBBPA and triclosan inhibit enzymes that are critical for BPA and E2 metabolism. https://doi.org/10.1289/EHP1329.
10.1289/EHP1329
Plastic-related endocrine disrupting chemicals significantly related to the increased risk of estrogen-dependent diseases in women.
Environmental research
OBJECTIVE:To evaluate the association between exposure to plastic-related endocrine-disrupting chemicals (EDCs), specifically Bisphenol A (BPA), Phthalates, Cadmium, and Lead, and the risk of estrogen-dependent diseases (EDDs) such as polycystic ovary syndrome (PCOS), endometriosis, or endometrial cancer by conducting a meta-analysis of relevant studies. METHODS:PubMed, Web of Science, and Cochrane Library databases were used for literature retrieval of articles published until the 21st of April 2023. Literature that evaluated the association between BPA, phthalates, cadmium, and/or lead exposure and the risk of PCOS, endometriosis, or endometrial cancer development or exacerbation were included in our analysis. STATA/MP 17.0 was used for all statistical analyses. RESULTS:Overall, 22 articles were included in our meta-analysis with a total of 83,641 subjects all of whom were females aged between 18 and 83 years old. The overall effect size of each study was as follows: endometriosis risk in relation to BPA exposure ES 1.82 (95% CI; 1.50, 2.20). BPA and PCOS risk ES 1.61 (95% CI; 1.39, 1.85). Phthalate metabolites and endometriosis risk; MBP ES 1.07 (95% CI; 0.86, 1.33), MEP ES 1.05 (95% CI; 0.87, 1.28), MEHP ES 1.15 (95% CI; 0.67, 1.98), MBzP ES 0.97 (95% CI; 0.63, 1.49), MEOHP ES 1.87 (95% CI; 1.21, 2.87), and MEHHP ES 1.98 (95% CI; 1.32, 2.98). Cadmium exposure and endometrial cancer risk ES 1.14 (95% CI; 0.92, 1.41). Cadmium exposure and the risk of endometriosis ES 2.54 (95% CI; 1.71, 3.77). Lead exposure and the risk of endometriosis ES 1.74 (95% CI; 1.13, 2.69). CONCLUSION:Increased serum, urinary, or dietary concentration of MBzP and MEHP in women is significantly associated with endometriosis risk. Increased cadmium concentration is associated with endometrial cancer risk.
10.1016/j.envres.2024.118966
Distinct metabolic signatures in blood plasma of bisphenol A-exposed women with polycystic ovarian syndrome.
Environmental science and pollution research international
Polycystic ovarian syndrome (PCOS) is a complicated endocrinopathy with an unclear etiology that afflicts fertility status in women. Although the underlying causes and pathophysiology of PCOS are not completely understood, it is suspected to be driven by environmental factors as well as genetic and epigenetic factors. Bisphenol A (BPA) is a weak estrogenic endocrine disruptor known to cause adverse reproductive outcomes in women. A growing relevance supports the notion that BPA may contribute to PCOS pathogenesis. Due to the indeterminate molecular mechanisms of BPA in PCOS endocrinopathy, we sought liquid chromatography with tandem mass spectrometry (LC-MS/MS), a metabolomics strategy that could generate a metabolic signature based on urinary BPA levels of PCOS and healthy individuals. Towards this, we examined urinary BPA levels in PCOS and healthy women by ELISA and performed univariate and chemometric analysis to distinguish metabolic patterns among high and low BPA in PCOS and healthy females, followed by pathway and biomarker analysis employing MetaboAnalyst 5.0. Our findings indicated aberrant levels of certain steroids, sphingolipids, and others, implying considerable disturbances in steroid hormone biosynthesis, linoleic, linolenic, sphingolipid metabolism, and various other pathways across target groups in comparison to healthy women with low BPA levels. Collectively, our findings provide insight into metabolic signatures of BPA-exposed PCOS women, which can potentially improve management strategies and precision medicine.
10.1007/s11356-023-26820-w
A mixture of five endocrine-disrupting chemicals modulates concentrations of bisphenol A and estradiol in mice.
Pollock Tyler,Weaver Rachel E,Ghasemi Ramtin,deCatanzaro Denys
Chemosphere
Most people in developed countries are exposed to multiple endocrine-disrupting synthetic chemicals. We previously showed that a single dose of triclosan, tetrabromobisphenol A (TBBPA), butyl paraben, propyl paraben, or di(2-ethylhexyl) phthalate elevated concentrations of bisphenol A (BPA) in mice. Here we investigated whether concurrent exposure to lower doses of these five chemicals could modulate concentrations of bisphenol A (BPA) or the natural estrogen, 17β-estradiol (E2). CF1 mice were injected subcutaneously with 0.1 or 0.5 mg of one chemical, or a 0.5 mg mixture containing 0.1 mg of each of all five chemicals, then given dietary 50 μg kgC-BPA. The mixture elevated C-BPA concentrations in the lungs, muscle, uterus, ovaries, kidney, and blood serum of female mice. When administered alone, triclosan and TBBPA elevated C-BPA concentrations in the uterus, ovaries, and blood serum. In another experiment, CF1 mice were injected subcutaneously with the 0.5 mg mixture containing 0.1 mg of all five chemicals, then E2 was measured in urine 2-12 h later. The mixture elevated E2 at 8 h after injection in female mice. No treatments significantly altered concentrations of C-BPA or E2 in male mice. These data show that these endocrine-disrupting chemicals interact in vivo, magnifying one another's effects, consistent with inhibition of enzymes that are critical for estrogen metabolism. These findings highlight the importance of considering exposure to multiple chemicals when assessing health outcomes and determining regulatory exposure limits.
10.1016/j.chemosphere.2017.11.030
Urinary concentration of personal care products and polycystic ovary syndrome: A case-control study.
Gu Jiayuan,Yuan Tao,Ni Ni,Ma Yuning,Shen Zhemin,Yu Xiaodan,Shi Rong,Tian Ying,Zhou Wei,Zhang Jun
Environmental research
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorder among females of reproductive age. Many emerging contaminants in personal care products have been confirmed with endocrine disruptive effects. We performed a case-control study to explore the association between the concentrations of certain emerging contaminants (organic UV filters, bisphenol A, and triclosan) and the risk of PCOS. Urine samples were collected from 40 women with PCOS (case group) and 83 healthy women (control group). No significant differences were found in detection rate or total concentrations of analytes in women with PCOS and controls (p > 0.05). In addition, no association was found between certain emerging contaminants and PCOS either in an unadjusted binary logistic regression model or in a model adjusted for potential confounders. However, with stratification according to body mass index, one organic UV filter - octocrylene(OC) was significantly associated with PCOS in women with BMI ≥ 24 (adjusted OR = 1.512, 95% CI: 1.043, 2.191). It's the first time to investigate the association between exposure of organic UV filters and PCOS risk. We conclude that there is positive association between OC and PCOS risk in obese and overweight women.
10.1016/j.envres.2018.09.014