Metal(loid)s as Potential Endocrine Disrupting Compounds and the Relationship with Anthropomorphic Measures and Semen Quality Endpoints
Open AccessThis dissertation entailed two separate yet related projects. Both the gonads and adipose tissue play a vital role in the production and regulation of hormone activity in the human body. Understanding the nature of hormone action is the first step to understanding how exposure to endocrine disrupting compound (EDCs), such as metal(loid)s, can impact human health. While some metal(loid)s are essential for human life, others may have health implications for spermatogenesis at environmentally relevant concentrations. The role that environmental chemicals play in fat metabolism and storage is more unclear. Organic tin (Sn) compounds may impact the body’s ability to regulate fat cell growth and production as well as other processes related to glucose and lipid regulation. Although the health effects of Sn compounds have been examined in animal studies, few human studies have examined organic Sn compounds in relation to weight and obesity.In the first study, we conducted a cross-sectional study of 4,462 adolescents (aged 12-19 years) and adults (aged 20-59 years) using the 2011-2016 cycles of the National Health and Nutrition Examination Survey (NHANES) and examined whether urinary total Sn, lead (Pb), and cadmium (Cd) concentrations independently predicted BMI, waist circumference (WC), or sagittal abdominal diameter (SAD). Results were weighted to be representative of the U.S. population, and reflected that higher quartiles of urinary Sn and Cd were associated with higher BMI and WC when compared to the lowest quartile, based on multivariate linear regression models adjusted for race, age, gender, SES, physical activity, and urinary flow rate. There were significant increases in SAD, WC, and BMI (β = 1.11, 3.63, and 1.60, respectively) in participants in the highest versus lowest quartiles of urinary Sn concentrations. Similar positive associations were found between BMI, SAD, and WC outcomes and Cd. These findings are novel, particularly for Sn, and demonstrate that metals such as Sn and Cd may influence adiposity in humans. Heavy metals in the environment and their influence on fat metabolism and storage need further study, given the potential for human exposure.The second study assessed the association between 15 creatinine-adjusted metal(loid)s and 7 measures of semen quality among 413 reproductive-aged men recruited from 16 U.S. counties between 2005–2009. Multi-metal(loid) multivariate linear regression models estimated the association between urinary concentrations of Cr, Co, Cu, Mo, Se, Zn, Sb, As, Ba, Cd, Pb, Tl, Sn, W, and U and semen quality endpoints. Models were selected based on results from LASSO regression. A positive association was observed between Sn and sperm morphology (β= 4.92 p= 0.045). Cr (β= 1.87, p= 0.003) and Cu (β= -1.30, p= 0.028) were positively and negatively associated with total sperm count, respectively. Cd (β= 12.73, p= 0.036) was positively associated with DNA fragmentation, whereas Cr negatively associated with (β = -5.08, p = 0.001). In this cohort of population-based men, we found evidence of both detrimental and beneficial associations between specific metal(loid)s and semen quality. Taken together, these dissertation findings, demonstrate the importance of EDCs, specifically metal(loid)s in explaining etiologic risk factors for hormone-mediated processes such as adiposity and spermatogenesis.
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