Zorimar Rivera-Núñez1, Pahriya Ashrap2, Emily S Barrett1, Deborah J Watkins2, Amber L Cathey2, Carmen M Vélez-Vega3, Zaira Rosario4, José F Cordero4, Akram Alshawabkeh5, John D Meeker6. 1. Department of Biostatistics and Epidemiology, Rutgers School of Public Health and Rutgers Environmental and Occupational Sciences Institute, Rutgers University, Piscataway, NJ, USA. 2. Department of Environmental Health Sciences, School of Public Health, University of Michigan Ann Arbor, MI, USA. 3. Graduate Program of Public Health, University of Puerto Rico, UPR Medical Sciences Campus, San Juan, PR, USA. 4. Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA, USA. 5. College of Engineering, Northeastern University, Boston, MA, USA. 6. Department of Environmental Health Sciences, School of Public Health, University of Michigan Ann Arbor, MI, USA. Electronic address: meekerj@umich.edu.
Abstract
BACKGROUND: Metal(loid)s have been associated to adverse birth outcomes in experimental and epidemiological studies, but the underlying mechanism(s) are not well understood. Endocrine disruption may be a mechanism by which the metal(loid)s impact birth outcomes. METHODS: Pregnant women were recruited through the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT). Urine, blood, demographic and pregnancy-related data were collected at recruitment and subsequent visits. Sixteen metal(loid)s were analyzed in urine and blood samples, while nine maternal hormones (corticotropin-releasing hormone (CRH), sex-hormone binding globulin (SHBG), estriol (E3), progesterone, testosterone, thyroid-stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), and free thyroxine (fT4)) were measured in serum samples from 815 singleton pregnancies. Linear mixed models with random intercepts were used to examine associations between metal(loid)s in blood and urine with hormone concentrations. RESULTS: Arsenic blood concentrations were significantly associated with increased levels in CRH (%Δ: 23.0, 95%CI: 8.4-39.6) and decreased levels in testosterone (%Δ: -16.3, 95%CI: -26.2--5.1). Cobalt, manganese, and lead blood concentrations were associated with small increases in SHBG (%Δ range: 3.3-4.2), E3 (%Δ range: 3.9-8.7) and progesterone (%Δ range: 4.1-6.3) levels, respectively. Nickel blood concentration was inversely associated with testosterone levels (%Δ -13.3, 95%CI: -18.7--7.6). Significant interactions were detected for the association between nickel and study visit in relation to CRH (p < 0.02) and testosterone levels (p < 0.01). CONCLUSION: Our analysis suggests that metal(loid)s may act as endocrine disruptors by altering prenatal hormone levels. This disruption may depend on specific windows of exposure during pregnancy. Additionally, some essential metal(loid)s such as managense and cobalt may be contributors to adverse maternal and fetal outcomes. The study of metal(loid)s as endocrine disruptors is in the early stages of epidemiological research and future studies are needed to further investigate these associations.
BACKGROUND: Metal(loid)s have been associated to adverse birth outcomes in experimental and epidemiological studies, but the underlying mechanism(s) are not well understood. Endocrine disruption may be a mechanism by which the metal(loid)s impact birth outcomes. METHODS: Pregnant women were recruited through the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT). Urine, blood, demographic and pregnancy-related data were collected at recruitment and subsequent visits. Sixteen metal(loid)s were analyzed in urine and blood samples, while nine maternal hormones (corticotropin-releasing hormone (CRH), sex-hormone binding globulin (SHBG), estriol (E3), progesterone, testosterone, thyroid-stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), and free thyroxine (fT4)) were measured in serum samples from 815 singleton pregnancies. Linear mixed models with random intercepts were used to examine associations between metal(loid)s in blood and urine with hormone concentrations. RESULTS: Arsenic blood concentrations were significantly associated with increased levels in CRH (%Δ: 23.0, 95%CI: 8.4-39.6) and decreased levels in testosterone (%Δ: -16.3, 95%CI: -26.2--5.1). Cobalt, manganese, and lead blood concentrations were associated with small increases in SHBG (%Δ range: 3.3-4.2), E3 (%Δ range: 3.9-8.7) and progesterone (%Δ range: 4.1-6.3) levels, respectively. Nickel blood concentration was inversely associated with testosterone levels (%Δ -13.3, 95%CI: -18.7--7.6). Significant interactions were detected for the association between nickel and study visit in relation to CRH (p < 0.02) and testosterone levels (p < 0.01). CONCLUSION: Our analysis suggests that metal(loid)s may act as endocrine disruptors by altering prenatal hormone levels. This disruption may depend on specific windows of exposure during pregnancy. Additionally, some essential metal(loid)s such as managense and cobalt may be contributors to adverse maternal and fetal outcomes. The study of metal(loid)s as endocrine disruptors is in the early stages of epidemiological research and future studies are needed to further investigate these associations.
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