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Early-life exposure to bisphenol A and reproductive-related outcomes in rodent models: a systematic review and meta-analysis.

ABSTRACT: We performed this meta-analysis to elucidate the associations between early-life BPA exposure and reproductive-related outcome indicators. The standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were measured by fixed-effects or random-effects models. The results revealed that BPA exposure at extremely-high dose (>50mg/kg/day) was significantly associated with negative reproductive-related outcomes (Prostate weight: SMD: -4.21; 95% Cl: -5.97, -2.44; Testis weight: SMD: -1.92; 95% Cl: -2.61, -1.23; Epididymis weight: SMD: -2.16; 95% Cl: -3.47, -0.86; Daily sperm production; SMD: -1.90; 95% Cl: -3.27, -0.53; Epididymal sperm count; SMD: -3.42; 95% Cl: -3.87, -2.97). Meanwhile, regardless of the dose, early-life BPA exposure could result in an adverse effect on sperm parameters of F1 generation male rodents at any period. Also, we found the non-monotonic dose response curves of BPA in specific tissues or organs, which may challenge the traditional mindset of "safe dose". This study demonstrated that bisphenol A exposure was relevant to adverse reproductive-related outcomes at specially appointed dose and period of life. Yet the assumption that no adverse effects can occur below the "safe" dose is suspected.

SUBMITTER: Ren X

PROVIDER: S-EPMC7585097 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Early-life exposure to bisphenol A and reproductive-related outcomes in rodent models: a systematic review and meta-analysis.

Ren Xiaohan X Ren Xiaohan X Zhang Tongtong T Chen Xinglin X Wei Xiyi X Tian Ye Y Li Guangyao G Zhang Xu X Zhang Wei W You Zebing Z Wang Shangqian S Qin Chao C

Aging 20200930 18

We performed this meta-analysis to elucidate the associations between early-life BPA exposure and reproductive-related outcome indicators. The standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were measured by fixed-effects or random-effects models. The results revealed that BPA exposure at extremely-high dose (>50mg/kg/day) was significantly associated with negative reproductive-related outcomes (Prostate weight: SMD: -4.21; 95% Cl: -5.97, -2.44; Testis weight: SMD: -1 ...[more]

PMID: 32996894

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Project description:BackgroundEarly-life exposure to bisphenol A (BPA) has been implicated to play a role in the development of obesity.ObjectiveA systematic review with meta-analyses of experimental rodent studies was conducted to answer the following question: does early-life exposure to BPA affect the obesity-related outcomes body weight, fat (pad) weight, and circulating and tissue levels of triglycerides, free fatty acids (FFA), and leptin?MethodsThe methodology was prespecified in a rigorous protocol using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) approach. Using PubMed and EMBASE, we identified 61 articles that met the inclusion criteria. The risk of bias and the methodological quality of these articles were assessed using the SYRCLE Risk of Bias tool, and a confidence-rating methodology was used to score the quality of evidence. Meta-analyses were performed using random effect models and standardized mean differences (SMDs), or, where possible, mean differences (MDs) were calculated.ResultsOverall summary estimates indicated significant positive associations between BPA and fat weight [SMD=0.67 (95% CI: 0.53, 0.81)], triglycerides [SMD=0.97 (95% CI: 0.53, 1.40)], and FFA [SMD=0.86 (95% CI: 0.50, 1.22)], and a nonsignificant positive association with leptin levels [MD=0.37 (95% CI: -0.14, 0.87)] and a significant negative association with body weight were estimated [MD=-0.22 (95% CI: -0.37, -0.06)]. Subgroup analyses revealed stronger positive associations for most outcome measures in males and at doses below the current U.S. reference dose of 50μg/kg/d compared with doses above the reference dose. It should be noted that there was substantial heterogeneity across studies for all outcomes assessed and that there was insufficient information to assess risk of bias for most studies.ConclusionsFindings from our systematic review suggest that early-life exposure to BPA may increase adiposity and circulating lipid levels in rodents. https://doi.org/10.1289/EHP1233.

Project description:Bisphenol-A is an important environmental contaminant due to the increased early-life exposure that may pose significant health-risks to various organisms including humans. This study aimed to use zebrafish as a toxicogenomic model to capture transcriptomic and phenotypic changes for inference of signaling pathways, biological processes, physiological systems and identify potential biomarker genes that are affected by early-life exposure to bisphenol-A. Phenotypic analysis using wild-type zebrafish larvae revealed BPA early-life exposure toxicity caused cardiac edema, cranio-facial abnormality, failure of swimbladder inflation and poor tactile response. Fluorescent imaging analysis using three transgenic lines revealed suppressed neuron branching from the spinal cord, abnormal development of neuromast cells, and suppressed vascularization in the abdominal region. Using knowledge-based data mining algorithms, transcriptome analysis suggests that several signaling pathways involving ephrin receptor, clathrin-mediated endocytosis, synaptic long-term potentiation, axonal guidance, vascular endothelial growth factor, integrin and tight junction were deregulated. Physiological systems with related disorders associated with the nervous, cardiovascular, skeletal-muscular, blood and reproductive systems were implicated, hence corroborated with the phenotypic analysis. Further analysis identified a common set of BPA-targeted genes and revealed a plausible mechanism involving disruption of endocrine-regulated genes and processes in known susceptible tissue-organs. The expression of 28 genes were validated in a separate experiment using quantitative real-time PCR and 6 genes, ncl1, apoeb, mdm1, mycl1b, sp4, U1SNRNPBP homolog, were found to be sensitive and robust biomarkers for BPA early-life exposure toxicity. The susceptibility of sp4 to BPA perturbation suggests its role in altering brain development, function and subsequently behavior observed in laboratory animals exposed to BPA during early life, which is a health-risk concern of early life exposure in humans. The present study further established zebrafish as a model for toxicogenomic inference of early-life chemical exposure toxicity.

Dataset Information

Early-life exposure to bisphenol A and reproductive-related outcomes in rodent models: a systematic review and meta-analysis.

Publications

Early-life exposure to bisphenol A and reproductive-related outcomes in rodent models: a systematic review and meta-analysis.

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