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Background: Persistent organic pollutants (POPs) are chemicals characterized by their environmental persistence. Evidence suggests that exposure to POPs, which is ubiquitous, is associated with microRNA (miRNA) dysregulation. miRNA are key regulators in many physiological processes. It is thus of public health concern to understand the relationships between POPs and miRNA as related to health outcomes., Objectives: This systematic review evaluated the relationship between widely recognized, intentionally manufactured, POPs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB]), with miRNA expression in both human and animal studies., Methods: We used PubMed and Embase to systematically search the literature up to September 29th, 2023. Search results for human and animal studies were included if they incorporated at least one POP of interest in relation to at least one miRNA. Data were synthesized to determine the direction and significance of associations between POPs and miRNA. We utilized ingenuity pathway analysis to review disease pathways for miRNA that were associated with POPs., Results: Our search identified 38 eligible studies: 9 in humans and 29 in model organisms. PFAS were associated with decreased expression of miR-19, miR-193b, and miR-92b, as well as increased expression of miR-128, miR-199a-3p, and miR-26b across species. PCBs were associated with increased expression of miR-15a, miR-1537, miR-21, miR-22-3p, miR-223, miR-30b, and miR-34a, as well as decreased expression of miR-130a and let-7b in both humans and animals. Pathway analysis for POP-associated miRNA identified pathways related to carcinogenesis., Discussion: This is the first systematic review of the association of POPs with miRNA in humans and model organisms. Large-scale prospective human studies are warranted to examine the role of miRNA as mediators between POPs and health outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) are intentionally produced persistent organic pollutants (POPs) that are resistant to environmental degradation. Previous in-vitro and in-vivo studies have shown that POPs can induce oxidative stress, which is linked to neurodegenerative diseases, cardiovascular diseases, and cancer. However, findings in epidemiological studies are inconsistent and an evidence synthesis study is lacking to summarize the existing literature and explore research gaps., Objective: We evaluated the effects of PFAS, PCBs, OCPs, and PBDEs, on oxidative stress biomarkers in epidemiological studies., Methods: A literature search was conducted in PubMed, Embase, and Cochrane CENTRAL to identify all published studies related to POPs and oxidative stress up to December 7 th , 2022. We included human observational studies reporting at least one exposure to POPs and an oxidative stress biomarker of interest. Random-effects meta-analyses on standardized regression coefficients and effect direction plots with one-tailed sign tests were used for quantitative synthesis., Results: We identified 33 studies on OCPs, 35 on PCBs, 49 on PFAS, and 12 on PBDEs. Meta-analyses revealed significant positive associations of α-HCH with protein carbonyls (0.035 [0.017, 0.054]) and of 4'4-DDE with malondialdehyde (0.121 [0.056, 0.187]), as well as a significant negative association between 2'4-DDE and total antioxidant capacity (TAC) (-0.042 [-0.079, -0.004]), all β [95%CI]. Sign tests showed a significant positive association between PCBs and malondialdehyde (p one-tailed  = 0.03). Additionally, we found significant negative associations of OCPs with acetylcholine esterase (p one-tailed  = 0.02) and paraoxonase-1 (p one-tailed  = 0.03). However, there were inconsistent associations of OCPs with superoxide dismutase, glutathione peroxidase, and catalase., Conclusions: Higher levels of OCPs were associated with increased levels of oxidative stress through increased pro-oxidant biomarkers involving protein oxidation, DNA damage, and lipid peroxidation, as well as decreased TAC. These findings have the potential to reveal the underlying mechanisms of POPs toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Exposure to lipophilic persistent organic pollutants (POPs) is ubiquitous. POPs are metabolic disrupting chemicals and are potentially diabetogenic., Methods: Using a multi-cohort study including overweight adolescents from the Study of Latino Adolescents at Risk (SOLAR, N = 301, 2001-2012) and young adults from the Southern California Children's Health Study (CHS, N = 135, 2014-2018), we examined associations of POPs and risk factors for type 2 diabetes. SOLAR participants underwent annual visits for a median of 2.2 years and CHS participants performed a single visit, during which a 2-h oral glucose tolerance test was performed. Linear mixed models were used to examine associations between plasma concentrations of POPs [4,4'-dichlorodiphenyldichloroethylene (4,4'-DDE), hexachlorobenzene (HCB), PCBs-153, 138, 118, 180 and PBDEs-154, 153, 100, 85, 47] and changes in glucose homeostasis across age and pubertal stage., Results: In SOLAR, exposure to HCB, PCB-118, and PBDE-153 was associated with dysregulated glucose metabolism. For example, each two-fold increase in HCB was associated with approximately 2 mg/dL higher glucose concentrations at 30 min (p = 0.001), 45 min (p = 0.0006), and 60 min (p = 0.03) post glucose challenge. Compared to individuals with low levels of PCB-118, individuals with high levels exhibited a 4.7 mg/dL (p = 0.02) higher glucose concentration at 15 min and a 3.6 mg/dL (p = 0.01) higher glucose concentration at 30 min. The effects observed with exposure to organochlorine compounds were independent of pubertal stages. PBDE-153 was associated with the development of dysregulated glucose metabolism beginning in late puberty. At Tanner stage 4, exposure to PBDE-153 was associated with a 12.7 mg/dL higher 60-min glucose concentration (p = 0.009) and a 16.1 mg*dl -1 *hr -1 higher glucose AUC (p = 0.01). These associations persisted at Tanner 5. In CHS, PBDE-153 and total PBDE were associated with similar increases in glucose concentrations., Conclusion: Our results suggest that childhood exposure to lipophilic POPs is associated with dysregulated glucose metabolism., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We conducted a systematic review and meta-analysis of the associations between prenatal exposure to persistent organic pollutants (POPs) and childhood obesity. We focused on organochlorines (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB], and polychlorinated biphenyls [PCBs]), perfluoroalkyl and polyfluoroalkyl substances (PFAS), and polybrominated diphenyl ethers (PBDEs) that are the POPs more widely studied in environmental birth cohorts so far. We search two databases (PubMed and Embase) through July/09/2021 and identified 33 studies reporting associations with prenatal organochlorine exposure, 21 studies reporting associations with prenatal PFAS, and five studies reporting associations with prenatal PBDEs. We conducted a qualitative review. Additionally, we performed random-effects meta-analyses of POP exposures, with data estimates from at least three prospective studies, and BMI-z. Prenatal DDE and HCB levels were associated with higher BMI z-score in childhood (beta: 0.12, 95% CI: 0.03, 0.21; I 2 : 28.1% per study-specific log increase of DDE and beta: 0.31, 95% CI: 0.09, 0.53; I 2 : 31.9% per study-specific log increase of HCB). No significant associations between PCB-153, PFOA, PFOS, or pentaPBDEs with childhood BMI were found in meta-analyses. In individual studies, there was inconclusive evidence that POP levels were positively associated with other obesity indicators (e.g., waist circumference)., (© 2021 World Obesity Federation.)

Purpose of Review: Non-alcoholic fatty liver disease (NAFLD) is the most prominent chronic liver disease in Western countries, affecting approximately 25% of the population worldwide. Sex-specific differences in the development of NAFLD are apparent. While obesity and insulin resistance are major contributors to the increasing prevalence of NAFLD, a growing body of literature suggests that exposure to persistent endocrine-disrupting chemicals (pEDCs) may also play a role. This review summarizes recent (2011 and later) scientific literature investigating exposures to pEDCs, specifically persistent organic pollutants (POPs), and NAFLD, with a focus on sex-specific associations., Recent Findings: The overwhelming majority of studies were conducted in single-sex animal models and provide biological evidence that exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin polychlorinated biphenyls, and other POPs or POP mixtures are negatively associated with liver health. There were four cross-sectional epidemiological studies in humans that reported associations for several POPs, including polychlorinated biphenyls and perfluorinated chemicals, with elevated liver enzymes. Only one of these studies, using a sample of gastric bypass surgery patients, examined sex-specific associations of POPs and liver enzymes, finding adverse associations among women only. The noticeable lack of studies investigating how differences (i.e., biochemical, physiological, and behavioral) between men and women may influence associations of pEDCs and NAFLD represents a large research gap in environmental health. Sexual dimorphism in metabolic processes throughout the body, including the liver, is established but often overlooked in the designs and analyses of studies. Other factors identified in this review that may also act to modulate associations of environmental chemicals and NAFLD are reproductive status and dietary nutrient intakes, which also remain understudied in the literature. Despite knowledge of sexual dimorphism in the actions of pEDCs, as well as in metabolic processes related to NAFLD development, few experimental or epidemiological studies have investigated sex-dependent associations. Future studies, especially those in humans, should be designed to address this research need. Consideration of other factors, such as reproductive status, dietary intakes, and mixtures of chemicals with varying endocrine-disrupting capabilities, should be explored.