The influence of unhealthy lifestyle on semen quality: results from a cross-sectional study and Mendelian randomization analysis

Background and aims: Unhealthy lifestyle may influence semen quality. This research aimed to investigate the association of unhealthy lifestyle with the risk of low semen quality and further to examine the causal relationship by Mendelian randomization (MR) method. Methods: The association of six unhealthy lifestyle habits (smoking, alcohol consumption, coffee consumption, sedentary behavior, obesity, and sleep disturbance) with semen quality was assessed using binary logistic regression analysis including 508 participants. A two-sample MR analysis for seven unhealthy lifestyle habits (smoking, alcohol consumption, caffeine consumption, cannabis consumption, sedentary behavior, obesity, and sleep disturbance) and semen quality was conducted. The principal analysis employed the inverse-variance-weighted (IVW) approach. The MR-pleiotropy residual sum and outlier (MR-PRESSO) tests and MR-Egger regression were implemented to evaluate horizontal pleiotropy. Sensitivity analyses were performed with Cochran’s Q test, leave-one-out analysis, and the funnel plot. Results: During the cross-sectional study, smoking, heavy alcohol and coffee consumption, and sedentary behavior were found to be significantly correlated with an elevated prevalence of low semen quality in the two models ( P < 0.05). In the IVW of MR analyses, a causal relationship between smoking/alcohol consumption/caffeine consumption/cannabis use/sedentary behavior and the semen quality–related genetic aspects (WFDC3, PATE1, CFAP45, SPEF1, CREM, SPATA20, SPATA9, SPATA46, CCDC103, CRISP2, EQTN, and SPAG11A) was observed ( P < 0.05). The robustness of the above results was found to be reliable with no pleiotropy. MR sensitivity analyses yielded consistent results. Conclusion: Our cross-sectional study indicated that smoking, heavy alcohol and coffee consumption, and sedentary behavior were significantly correlated with low semen quality. The MR study supported a causal association between smoking/alcohol consumption/caffeine consumption/cannabis use/sedentary behavior and low semen quality.