Intergenerational Effects of Endocrine-Disrupting Compounds: A Review of the Michigan Polybrominated Biphenyl Registry

Curtis, Sarah W.; Conneely, Karen N.; Marder, M. Elizabeth; Terrell, Metrecia L.; Marcus, Michele; Smith, Alicia K.

doi:10.2217/epi-2017-0174

Cited by 18 publications

(26 citation statements)

References 88 publications

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“…This cohort has reported many endocrine-related and reproductive health concerns, such as thyroid disease, spontaneous abortions, earlier age of menarche, and genitourinary conditions in male offspring, as well as breast cancer, digestive cancer, and lymphomas [24][25][26][27][28][29][30][31][32][33]. In general, the people who were exposed in utero or in childhood were found to be particularly susceptible to endocrine-related conditions [34].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways. After multiple test correction (FDR <0.05), 1890 CpG sites associated with total PBB levels. These CpGs were not enriched in any particular biological pathway, but were enriched in enhancer and insulator regions, and depleted in regions near the transcription start site or in CpG islands (p < 0.05). They were also more likely to be in ARNT and ESR2 transcription factor binding sites (p = 3.27e-23 and p = 1.62e-6, respectively), and there was significant overlap between CpGs associated with PBB and CpGs associated with estrogen (p < 2.2e-16). PBBassociated CpGs were also enriched for CpGs known to be associated with gene expression in blood (eQTMs) (p < 0.05). These eQTMs were enriched for pathways related to immune function and endocrine-related autoimmune disease (FDR <0.05). These results indicate that exposure to PBB is associated with differences in epigenetic marks that suggest that it is acting similarly to estrogen and is associated with dysregulated immune system pathways. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…Our study did not evaluate whether age at exposure altered any of the associations between PBB and reproductive health outcomes as we did not have a large enough sample size with maternal PCB/PBB levels. Therefore, future studies should evaluate whether women who were exposed to PBB or PCB in utero have health effects not seen in the women exposed later in life, as has been reported by previous studies 3,11,30,52,53 .…”

Section: Discussionmentioning

confidence: 93%

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

Neblett

Curtis

Gerkowicz

et al. 2020

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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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“…In the aftermath, the people who were believed to have the highest direct exposure – people living on or obtaining food from quarantined farms and the Michigan Chemical Company’s workers and their families – were recruited to investigate the long-term health effects of PBB exposure. These participants, their children, and other members of the community have been followed for the past 40 years as part of the Michigan PBB Registry and have had their current serum levels of PBB regularly assessed, as well as their exposure to the structurally-related polychlorinated biphenyl (PCB), which they were continuously exposed to from typical environmental sources [7–9].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, PBBs are transferred across the placenta and are present in the breast milk of exposed women, meaning that their children, even those born decades after the incident, can be exposed to PBB during development [12]. People exposed to PBB in utero or as children have been shown to have an increased risk of endocrine-related health conditions, and may experience unique problems compared to those exposed as adults [9]. For example, women exposed to PBB in utero were found to be at increased risk for earlier menarche and spontaneous abortions, while women exposed as adults were not found to be at increased risk [13–15].…”

Section: Introductionmentioning

confidence: 99%

“…Because PBB exposure (unlike PCB exposure) in this cohort occurred during a single, unique time-point, we can also estimate participants’ age when exposed to PBB, and test whether their age at exposure to PBB and current PBB level predict thyroid function. Additionally, because many of the health effects associated with PBB were in those who were exposed when they were young [9, 14, 15, 17, 18], we can then test whether the association between PBB exposure and thyroid function differs in people exposed before age 16 compared to those exposed after age 16.…”

Section: Introductionmentioning

confidence: 99%

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Thyroid hormone levels associate with exposure to polychlorinated biphenyls and polybrominated biphenyls in adults exposed as children

et al. 2019

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Background Michigan residents were directly exposed to endocrine-disrupting compounds, polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB). A growing body of evidence suggests that exposure to certain endocrine-disrupting compounds may affect thyroid function, especially in people exposed as children, but there are conflicting observations. In this study, we extend previous work by examining age of exposure’s effect on the relationship between PBB exposure and thyroid function in a large group of individuals exposed to PBB. Methods Linear regression models were used to test the association between serum measures of thyroid function (total thyroxine (T 4 ), total triiodothyronine (T 3 ), free T 4 , free T 3 , thyroid stimulating hormone (TSH), and free T 3 : free T 4 ratio) and serum PBB and PCB levels in a cross-sectional analysis of 715 participants in the Michigan PBB Registry. Results Higher PBB levels were associated with many thyroid hormones measures, including higher free T 3 ( p = 0.002), lower free T 4 ( p = 0.01), and higher free T 3 : free T 4 ratio ( p = 0.0001). Higher PCB levels were associated with higher free T 4 ( p = 0.0002), and higher free T 3 : free T 4 ratio (p = 0.002). Importantly, the association between PBB and thyroid hormones was dependent on age at exposure. Among people exposed before age 16 ( N = 446), higher PBB exposure was associated with higher total T 3 (p = 0.01) and free T 3 ( p = 0.0003), lower free T 4 ( p = 0.04), and higher free T 3 : free T 4 ratio (p = 0.0001). No significant associations were found among participants who were exposed after age 16. No significant associations were found between TSH and PBB or PCB in any of the analyses conducted. Conclusions This suggests that both PBB and PCB are associated with thyroid function, particularly among those who were exposed as children or prenatally. Electronic supplementary material The online version of this article (10.1186/s12940-019-0509-z) contains supplementary material, which is available to authorized users.

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Intergenerational Effects of Endocrine-Disrupting Compounds: A Review of the Michigan Polybrominated Biphenyl Registry

Cited by 18 publications

References 88 publications

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

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

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

Thyroid hormone levels associate with exposure to polychlorinated biphenyls and polybrominated biphenyls in adults exposed as children

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