Sperm DNA Damage Caused by the Abnormal Methylation of Rad54 Promoter Region Caused by Folic Acid Deficiency

Background: Sperm DNA injury is one of the common causes of male infertility. Folic acid deficiency would increase the methylation level of the important genes, including DNA double-strand Break(DSB) repair pathway. This study aims to preliminarily investigate the underlying mechanism on how the abnormal methylation caused by folic acid deficiency aggravates sperm DNA damage. Methods: Through reduced representation bisulfite sequencing(RRBS), Global DNA methylation of sperm of patients in the low folic acid group and the high folic acid group was analyzed, and differential methylation genes were selected. Animal models and cell line were applied to validate the mechanism and function of the genes of interest. Findings: We analyzed the correlation between Seminal plasma folic acid concentration and semen parameters in 157 infertility patients and 91 sperm donor volunteers, and found that there was a significant negative correlation between seminal folic acid concentration and sperm DFI (r=-1.495, p