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Exposure of environmental Bisphenol A in relation to routine sperm parameters and sperm movement characteristics among fertile men.

ABSTRACT: Although several human studies have examined bisphenol A (BPA) exposure in relation to routine sperm parameters, evidence of BPA's effects on sperm movement characteristics is limited. We examined associations of BPA exposure with sperm parameters including sperm movement characteristics among fertile men. The cross-sectional study was conducted in Sandu County, Guizhou Province, China. Subjects provided semen samples analyzed by computer-aided sperm analysis (CASA) system and urine samples for BPA assay. They were invited to complete an in-person interview with a structured questionnaire to obtain demographics, lifestyle factors, etc. In final analyses, 500 subjects were included. We used multivariate linear regression analyses to estimate associations between BPA and sperm parameters after adjusting for potential confounders. BPA was detected in 73.6% of urine samples, with a geometric mean of 0.44??g/gCreatinine. Compared with subjects of undetected BPA, subjects with detected BPA had increased Linearity (LIN, ?: 2.19, 95% confidence interval (CI): 0.37, 4.0), Straightness (STR, ?: 1.47, 95% CI: 0.19, 2.75), Wobble (WOB, ?: 1.75, 95% CI: 0.26, 3.25), reduced Amplitude of lateral head displacement (ALH, ?: -0.26, 95% CI: -0.5, -0.02) and Mean angular displacement (MAD, ?: -2.17, 95% CI: -4.22, -0.11). Subjects in the highest tertile of creatinine-adjusted BPA group had lower sperm concentration than those with undetected BPA. Dose-response relationships of BPA with LIN, WOB, ALH, MAD and sperm concentration were demonstrated by statistically significant trends across tertiles of creatinine-adjusted BPA concentrations. Similar results were obtained using unadjusted BPA concentrations. Exposure to environmental BPA would decrease sperm concentration and sperm swing characteristics (ALH and MAD), and increase sperm velocity ratios (LIN, STR and WOB), which might mediate further effects on impaired male fecundity.

SUBMITTER: Ji H

PROVIDER: S-EPMC6277384 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Exposure of environmental Bisphenol A in relation to routine sperm parameters and sperm movement characteristics among fertile men.

Ji Honglei H Miao Maohua M Liang Hong H Shi Huijuan H Ruan Dasheng D Li Yongbo Y Wang Jian J Yuan Wei W

Scientific reports 20181203 1

Although several human studies have examined bisphenol A (BPA) exposure in relation to routine sperm parameters, evidence of BPA's effects on sperm movement characteristics is limited. We examined associations of BPA exposure with sperm parameters including sperm movement characteristics among fertile men. The cross-sectional study was conducted in Sandu County, Guizhou Province, China. Subjects provided semen samples analyzed by computer-aided sperm analysis (CASA) system and urine samples for ...[more]

PMID: 30510208

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Project description:Several experimental and observational studies have demonstrated the antiandrogenicity of several phthalates. However, there is limited evidence of an association between phthalate exposure in adult life and semen quality. The aim of this study was to examine phthalate exposure during adulthood in relation to semen quality in fertile US men. This multi-center cross-sectional study included 420 partners of pregnant women who attended a prenatal clinic in one of five US cities during 1999-2001. Nine phthalate metabolites [mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP)], as well as mono-n-butyl phthalate (MBP) and mono-isobutyl phthalate (MiBP), mono (three carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP), and monoethyl phthalate (MEP)] were measured in urine collected at the same time as the semen sample. We regressed natural log-transformed (ln) sperm concentration, ln(total sperm count), ln(total motile sperm count), percent motile spermatozoa, and percent spermatozoa with normal morphology on each of the nine natural log-transformed metabolite concentrations and on the molar-weighted sum of DEHP metabolites in separate models. We fit unadjusted models and models that adjusted for confounders determined a priori. In unadjusted models, ln(MiBP) was significantly and positively associated with motility and ln(MBzP) significantly negatively associated with ln(total sperm count). In adjusted linear models, urinary metabolite concentrations of DEHP, DBP, DEP, and DOP were not associated with any semen parameter. We found an inverse association between ln(MBzP) concentrations and sperm motility (? = -1.47, 95% CI: -2.61, -0.33), adjusted for ln(creatinine concentration), geographic location, age, race, smoking status, stress, recent fever, time from sample collection and time to complete analysis. Several sensitivity analyses confirmed the robustness of these associations. This study and the available literature suggest that impacts of adult exposure to phthalates at environmental levels on classical sperm parameters are likely to be small.

Project description:Environmental BPA exposure has been shown to impact human sperm concentration and motility, as well as rodent spermatogenesis. However, it is unclear whether BPA exposure is associated with alteration in DNA hydroxymethylation, a marker for epigenetic modification, in human sperm. A genome-wide DNA hydroxymethylation study was performed using sperm samples of men who were occupationally exposed to BPA. Compared with controls who had no occupational BPA exposure, the total levels of 5-hydroxymethylcytosine (5hmc) increased significantly (19.37% increase) in BPA-exposed men, with 72.69% of genome regions harboring 5hmc. A total of 9,610 differential 5hmc regions (DhMRs) were revealed in BPA-exposed men relative to controls, which were mainly located in intergenic and intron regions. These DhMRs were composed of 8,670 hyper-hMRs and 940 hypo-hMRs, affecting 2,008 genes and the repetitive elements. The hyper-hMRs affected genes were enriched in pathways associated with nervous system, development, cardiovascular diseases and signal transduction. Additionally, enrichment of 5hmc was observed in the promoters of eight maternally expressed imprinted genes in BPA-exposed sperm. Some of the BPA-affected genes, for example, MLH1, CHD2, SPATA12 and SPATA20 might participate in the response to DNA damage in germ cells caused by BPA. Our analysis showed that enrichment of 5hmc both in promoters and gene bodies is higher in the genes whose expression has been detected in human sperm than those whose expression is absent. Importantly, we observed that BPA exposure affected the 5hmc level in 11.4% of these genes expressed in sperm, and in 6.85% of the sperm genome. Finally, we also observed that BPA exposure tends to change the 5hmc enrichment in the genes which was previously reported to be distributed with the trimethylated Histone 3 (H3K27me3, H3K4me2 or H3K4me3) in sperm. Thus, these results suggest that BPA exposure likely interferes with gene expression via affecting DNA hydroxymethylation in a way partially dependent on trimethylation of H3 in human spermatogenesis. Our current study reveals a new mechanism by which BPA exposure reduces human sperm quality.

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Project description:IntroductionTrained Immunity represents a novel revolutionary concept of the immunological response involving innate immune cells. Bisphenol A is a well-known endocrine disrupter, widely disseminated worldwide and accumulated in the human body. Due to the increased interest regarding the effects of plastic-derived compounds on the immune system, our purpose was to explore whether BPA was able to induce trained immunity in human primary monocytes in vitro using low environmental concentrations.Materials and methodsWe extracted BPA from the serum of 10 healthy individuals through a liquid-liquid extraction followed by a solid phase extraction and measured the concentration using an HPLC system coupled to a triple quadrupole mass spectrometer. In parallel, monocytes were isolated from whole blood and acutely stimulated or trained with BPA at three different concentrations (1 nM, 10 nM, 20 nM). Pro- and anti-inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-10) production were assessed after 24 hours of acute stimulation and after Lipopolysaccharide (LPS) rechallenge. A comprehensive overview of the metabolic changes after BPA acute stimulation and trained immunity induction was assessed through extracellular lactate measurements, Seahorse XFb metabolic flux analysis and ROS production.ResultsMonocytes primed with BPA showed increased pro- and anti-inflammatory cytokine responses upon restimulation, sustained by the modulation of the immunometabolic circuits. Moreover, we proved the non-toxic effect of BPA at each experimental concentration by performing an MTT assay. Additionally, correlation analysis were performed between pro- and anti-inflammatory cytokines production after LPS acute stimulation or BPA-mediated trained immunity and BPA serum concentrations showing a significant association between TNF-α and BPA circulating levels.DiscussionOverall, this study pointed out for the first time the immunological effects of an environmental chemical and plastic-derived compound in the induction of trained immunity in a healthy cohort.

Project description:What are the characteristics of progesterone-induced (CatSper-mediated) single cell [Ca2+]i signals in spermatozoa from sub-fertile men and how do they relate to fertilizing ability?Single cell analysis of progesterone-induced (CatSper-mediated) [Ca2+]i showed that reduced progesterone-sensitivity is a common feature of sperm from sub-fertile patients and is correlated with fertilization rate.Stimulation with progesterone is a widely used method for assessing [Ca2+]i mobilization by activation of CatSper in human spermatozoa. Although data are limited, sperm population studies have indicated an association of poor [Ca2+]i response to progesterone with reduced fertilization ability.This was a cohort study using semen samples from 21 donors and 101 patients attending the assisted conception unit at Ninewells Hospital Dundee who were undergoing ART treatment. Patients were recruited from January 2016 to June 2017.Semen donors and patients were recruited in accordance with local ethics approval (13/ES/0091) from the East of Scotland Research Ethics Service (EoSRES) REC1. [Ca2+]i responses were examined by single cell imaging and motility parameters assessed by computer-assisted sperm analysis (CASA).For analysis, patient samples were divided into three groups IVF(+ve) (successful fertilization; 62 samples), IVF-FF (failed fertilization; eight samples) and ICSI (21 samples). A further 10 IVF samples showed large, spontaneous [Ca2+]i oscillations and responses to progesterone could not be analysed. All patient samples loaded with the [Ca2+]i-indicator fluo4 responded to progesterone stimulation with a biphasic increase in fluorescence (transient followed by plateau) which resembled that seen in progesterone-stimulated donor samples. The mean normalized response (progesterone-induced increase in fluorescence normalized to resting level) was significantly smaller in IVF-FF and ICSI patient groups than in donors. All samples were further analysed by plotting, for each cell, the relationship between resting fluorescence intensity and the progesterone-induced fluorescence increment. In donor samples these plots overlaid closely and had a gradient of ? 2 and plots for most IVF(+ve) samples closely resembled the donor distribution. However, in a subset (? 10%) of IVF(+ve) samples, 3/8 IVF-FF samples and one-third of ICSI samples the gradient of the plot was significantly lower, indicating that the response to progesterone of the cells in these samples was abnormally small. Examination of the relationship between gradient (regression coefficient of the plot) in IVF samples and fertilization rate showed a positive correlation. In IVF-FF and ICSI groups, the proportion of cells in which a response to progesterone could be detected was significantly lower than in donors and IVF (+ve) patients. Approximately 20% of cells in donor, IVF(+ve) and ICSI samples generated [Ca2+]i oscillations when challenged with progesterone but in IVF-FF samples only ? 10% of cells generated oscillations and there was a significantly greater proportion of samples where no oscillations were observed. Levels of hyperactivated motility were lower in IVF(+ve) and IVF-FF groups compared to controls, IVF-FF also having lower levels than IVF(+ve).This is an in vitro study and caution must be taken when extrapolating these results in vivo.This study reveals important details of impaired [Ca2+]i signalling in sperm from sub-fertile men that cannot be detected in population studies.This study was funded by a MRC project grant (MR/M012492/1; MR/K013343/1). Additional funding was provided by Chief Scientist Office/NHS research Scotland.

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Exposure of environmental Bisphenol A in relation to routine sperm parameters and sperm movement characteristics among fertile men.

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Exposure of environmental Bisphenol A in relation to routine sperm parameters and sperm movement characteristics among fertile men.

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