Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

Curtis, Sarah W.; Cobb, Dawayland; Kilaru, Varun; Terrell, Metrecia L.; Kennedy, Elizabeth M.; Marder, M. Elizabeth; Barr, Dana Boyd; Marsit, Carmen J.; Marcus, Michele; Conneely, Karen N.; Smith, Alicia K.

doi:10.1080/15592294.2019.1565590

Cited by 39 publications

(38 citation statements)

References 91 publications

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“…Serum lipid measurement. As previously described 41,47 , a Triglyceride Quantification Assay Kit (Abnova Corporation) was used to measure the total triglyceride content in serum, and a Cholesterol Assay Kit (Caymen Chemical Company) was used to measure total cholesterol content in serum. Both were done according to manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

Examining Reproductive Health Outcomes in Females Exposed to Polychlorinated Biphenyl and Polybrominated Biphenyl

Neblett

Curtis

Gerkowicz

et al. 2020

Sci Rep

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In 1973, accidental contamination of Michigan livestock with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals that have been followed for > 40 years. Besides being exposed to PBBs, this cohort has also been exposed to polychlorinated biphenyls (PCBs), a structurally similar class of environmental pollutants, at levels similar to average US exposure. In this study, we examined the association between current serum PCB and PBB levels and various female reproductive health outcomes to build upon previous work and inconsistencies. participation in this cross-sectional study required a blood draw and completion of a detailed health questionnaire. Analysis included only female participants who had participated between 2012 and 2015 (N = 254). Multivariate linear and logistic regression models were used to identify associations between serum PCB and PBB levels with each gynecological and infertility outcome. Additionally, a generalized estimating equation (GEE) model was used to evaluate each pregnancy and birth outcome in order to account for multiple pregnancies per woman. We controlled for age, body mass index, and total lipid levels in all analyses. A p-value of <0.05 was used for statistical significance. Among the women who reported ever being pregnant, there was a significant negative association with higher total PCB levels associating with fewer lifetime pregnancies (β = −0.11, 95% CI = −0.21 to −0.005, p = 0.04). There were no correlations between serum PCB levels and the self-reported gynecological outcomes (pelvic inflammatory disease, endometriosis, polycystic ovarian syndrome, or uterine fibroids). No associations were identified between serum PCB levels and the prevalence of female infertility in women reporting ever having sexual intercourse with a male partner. There were no associations identified between serum PCB levels and pregnancy outcomes (singleton live births or miscarriages) or birth outcomes (preterm birth, birth weight, birth defects, hypertensive disorders of pregnancy, or gestational diabetes). PBB was not associated with any outcome. Further research is needed to determine if and how PCB may reduce pregnancy number. Polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs) are synthetic chemicals that were once used as coolants in electrical equipment and as flame retardants in the manufacturing of plastics and electronics, respectively 1,2. Although the production of PCBs ceased in 1977 and PBBs in 1976, concern over their health effects remains because of their continued persistence in the environment, the pervasiveness of their exposure in

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Section: Methodsmentioning

confidence: 99%

Examining Reproductive Health Outcomes in Females Exposed to Polychlorinated Biphenyl and Polybrominated Biphenyl

Neblett

Curtis

Gerkowicz

et al. 2020

Sci Rep

Self Cite

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“…Using our in vitro model of human spermatogenesis, we next sought to determine whether PBB153 had an effect on either de novo or maintenance DNA methyltransferase activity, hypothesizing that a decrease in activity of either enzyme could explain the decreases in methylation levels observed on promoter and heterochromatic regions in peripheral blood cells 19 and in ICRs and DMRs in our current study. Using concentrations of PBB153 from our in vitro study (Fig.…”

Section: Pbb153 Decreases Methylation At Icrs Of Imprinting Genes In mentioning

confidence: 99%

Detrimental effects of flame retardant, PBB153, exposure on sperm and future generations

Greeson

Fowler

Estave

et al. 2020

Sci Rep

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In 1973, the Velsicol Chemical Company, which manufactured FireMaster, a brominated flame retardant, and NutriMaster, a nutritional supplement, mistakenly shipped hundreds of pounds of FireMaster to grain mills around Michigan where it was incorporated into animal feed and then into the food chain across the state. An estimated 6.5 million Michigan residents consumed polybrominated biphenyl (PBB)-laced animal products leading to one of the largest agricultural accidents in U.S. history. To date, there have been no studies investigating the effects of PBB on epigenetic regulation in sperm, which could explain some of the endocrine-related health effects observed among children of PBB-exposed parents. Fusing epidemiological approaches with a novel in vitro model of human spermatogenesis, we demonstrate that exposure to PBB153, the primary component of FireMaster, alters the epigenome in human spermatogenic cells. Using our novel stem cell-based spermatogenesis model, we show that PBB153 exposure decreases DNA methylation at regulatory elements controlling imprinted genes. Furthermore, PBB153 affects DNA methylation by reducing de novo DNA methyltransferase activity at increasing PBB153 concentrations as well as reducing maintenance DNA methyltransferase activity at the lowest tested PBB153 concentration. Additionally, PBB153 exposure alters the expression of genes critical to proper human development. Taken together, these results suggest that PBB153 exposure alters the epigenome by disrupting methyltransferase activity leading to defects in imprint establishment causing altered gene expression, which could contribute to health concerns in the children of men exposed to PBB153. While this chemical is toxic to those directly exposed, the results from this study indicate that the epigenetic repercussions may be detrimental to future generations. Above all, this model may be expanded to model a multitude of environmental exposures to elucidate the effect of various chemicals on germline epigenetics and how paternal exposure may impact the health of future generations. In recent years, a major focus of research has been the Developmental Origins of Health and Disease (DOHaD) 1. A component of DOHaD research examines the impact of pre-and post-conception risk factors on long-term health and disease progression in adulthood. In terms of pre-conception risk factors, many researchers report that toxicants and environmental exposures can potentially alter the epigenome in gametes, giving these exposures the potential to ultimately impact the health of the next generation 2-5. In 1973, farms across Michigan mistakenly received cattle feed mixed with FireMaster BP-6, a chemical flame retardant composed of a mixture of polybrominated biphenyl compounds (PBBs), rather than NutriMaster, a food additive that increased milk production in farm animals 6-9. PBB-laced animal products were consumed by millions of residents, and the decline in animal

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“…AgeGuess was applied to an independent dataset GSE116339 generated on the EPIC arrays (Curtis et al, 2019). This dataset was publicly available from the database Gene Expression Omnibus (Clough and Barrett, 2016) and provided the methylomes of 679 whole blood samples with the chronological ages (Curtis et al, 2019). AgeGuess finally selected 388 CpG features to establish the age prediction model.…”

Section: Evaluating Ageguess On Another Methylomic Dataset On the Epimentioning

confidence: 99%

AgeGuess, a Methylomic Prediction Model for Human Ages

Gao

Liu

Song

et al. 2020

Front. Bioeng. Biotechnol.

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Aging was a biological process under regulations from both inherited genetic factors and various molecular modifications within cells during the lifespan. Multiple studies demonstrated that the chronological age may be accurately predicted using the methylomic data. This study proposed a three-step feature selection algorithm AgeGuess for the age regression problem. AgeGuess selected 107 methylomic features as the gender-independent age biomarkers and the Support Vector Regressor (SVR) model using these biomarkers achieved 2.0267 in the mean absolute deviation (MAD) compared with the real chronological ages. Another regression algorithm Ridge achieved a slightly better MAD 1.9859 using the same biomarkers. The gender-independent age prediction models may be further improved by establishing two gender-specific models. And it's interesting to observe that there were only two methylation biomarkers shared by the two gender-specific biomarker sets and these two biomarkers were within the two known age-associated biomarker genes CALB1 and KLF14.

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Exposure to polybrominated biphenyl (PBB) associates with genome-wide DNA methylation differences in peripheral blood

Cited by 39 publications

References 91 publications

Examining Reproductive Health Outcomes in Females Exposed to Polychlorinated Biphenyl and Polybrominated Biphenyl

Examining Reproductive Health Outcomes in Females Exposed to Polychlorinated Biphenyl and Polybrominated Biphenyl

Detrimental effects of flame retardant, PBB153, exposure on sperm and future generations

AgeGuess, a Methylomic Prediction Model for Human Ages

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