Background: A normal thyroid physiology is crucial for the maintenance of male reproductive health. Changes in thyroid hormones may represent an intermediate biological mechanism linking phthalate exposure and potential adverse health effects on male reproduction.
Objective: To investigate the mediating role of thyroid function on the association between phthalate exposure and semen quality.
Method: Serum thyroid hormones, semen quality and repeated measures of urinary phthalate metabolites were determined among 509 reproductive-aged men in Wuhan, China. Cross-sectional associations between urinary phthalate metabolites, serum thyroid hormones and semen quality were explored using multivariable linear regressions. A mediation analysis was conducted to explore the role of thyroid function on the association of phthalate exposure with semen quality.
Results: Significant dose-dependent relationships were found across quartiles of monoethyl phthalate (MEP) with decreasing serum free thyroxine (FT4), which, in turn, was negatively associated with percentage of normal morphology (p for trend = 0.04). Also, we found that the proportions of di-(2-ethylhexyl)-phthalate metabolites excreted as mono-(2-ethylhexyl) phthalate (%MEHP) were negatively associated with serum thyroid-stimulating hormone (TSH) (all p for trends <0.05), which, in turn, was positively associated with progressive and total sperm motility (p for trends = 0.04 and 0.03, respectively). The mediation analysis indicated that higher urinary MEP was significantly associated with a decreasing percentage of normal morphology after controlling for thyroid hormones, and 17% of the association was mediated by serum FT4.
Conclusions: Higher urinary MEP and %MEHP were associated with decreasing serum thyroid hormones, which in turn were associated with altered semen quality. Mediation analysis indicated that serum FT4 was a possible mediator of the association between urinary MEP and proportion of normal sperm morphology.
Keywords: Human; Mediation; Phthalate; Semen quality; Thyroid function.
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