Objective  To investigate the association of semen metal concentration and estrogen receptor alpha gene (ESR1) with semen quality in human and to provide epidemiological evidences for researches on mechanism of metal's effect on semen quality.

  Methods  A hospital-based case-control study was conducted among 91 cases and 91 controls with abnormal and normal semen quality recruited from the attendees having semen examination in a reproductive medicine center of a tertiary grade A hospital in Shenzhen city from September 2016 to November 2017. A questionnaire interview and laboratory detection on concentrations of 11 metals and ESR1 expression in semen were carried out in the participants.

  Results  Compared to the controls, the cases had significantly higher median seminal concentration (μg/L) of chromium (Cr: 2.12 vs. 1.64), manganese (Mn: 9.61 vs. 8.18), copper (Cu: 107.00 vs. 91.40), and thallium (Tl: 0.23 vs. 0.19) (all P < 0.01). The relative mRNA expression level of ESR1 gene in the semen of the cases (– 0.66 ± 4.85) and the controls (0.63 ± 3.96) was significantly different (t = – 1.974, P < 0.05). The results of unconditional multivariate logistic regression demonstrated that after adjusting for age, body mass index (BMI) and abstinence time, in contrast to those with the lowest quartile concentrations, the participants with the highest quartile concentration of Cr, Mn and Cu were at increased risk of abnormal semen quality, with the odds ratio (OR) (95% confidence interval 95% CI) of 3.16 (1.32 – 7.58), 3.58 (1.45 – 8.83) and 3.17 (1.32 – 7.64), respectively; the participants with the third and the highest quartile concentration of Tl were also at increased risk of abnormal semen quality, with the OR (95% CI) of 2.77 (1.15 – 6.70) and 3.96 (1.55 – 10.08) compared to the participants with the lowest quartile concentration. The participants with a low ESR1 gene expression in semen had an increased risk of abnormal semen quality (OR = 1.89, 95% CI: 1.04 – 3.46) in comparison with those with a high ESR1 gene expression. The results of multivariate linear regression analysis revealed that in comparison to the lowest quartile concentration, the highest quartile seminal concentration of Tl was reversely correlated with ESR1 gene expression (b = – 2.49, 95% CI: – 4.44 – – 0.54) after adjusting for age, BMI and abstinence time. Mediation analysis indicated that ESR1 gene expression contributed to a significant proportion of the correlation between Tl and semen quality, accounting for 18.6% of the total effect.

  Conclusion  High metal concentration of Cr, Mn, Cu, and Tl and low expression of ESR1 gene in semen are risk factors for abnormal semen quality. The adverse effect of Tl on semen quality is partially mediated by ESR1 gene expression.