The enigmatic interplay of immune cells and abnormal spermatozoa throughMendelian randomization.

Purpose: Abnormal spermatozoa significantly impact reproductive health, affecting fertility rates, potentially prolonging conception time, and increasing the risk ofmiscarriages. This study employsMendelian randomization to explore their potential linkwith immune cells, aiming to reveal their potential causal association and wider implications for reproductive health. Methods: We conducted forward and reverse Mendelian randomization analyses to explore the potential causal connection between 731 immune cell signatures and abnormal spermatozoa. Using publicly available genetic data, we investigated various immune signatures such as median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP). Robustness was ensured through comprehensive sensitivity analyses assessing consistency, heterogeneity, and potential horizontal pleiotropy. The MR study produced a statistically significant p-value of .0000684, Bonferroni-corrected for the 731 exposures. Results: The Mendelian randomization analysis revealed strong indications of a reciprocal relationship between immune cell pathways and sperm integrity. When examining immune cell exposure, a potential causal link with abnormal sperm was observed in 35 different types of immune cells. Conversely, the reverse Mendelian randomization results indicated that abnormal sperm might causally affect 39 types of immune cells. These outcomes suggest a potential mutual influence between alterations in immune cell functionality and the quality of spermatozoa. Conclusion: This study highlights the close link between immune responses and sperm development, suggesting implications for reproductive health and immune therapies. Further researchmay offer crucial insights into male fertility and immune disorders. [ABSTRACT FROM AUTHOR]