Proteomic profiling identifies circulating soluble MCAM/CD146 as a candidate biomarker for abnormal semen parameters in male infertility

BACKGROUND: A growing body of evidence suggests that male infertility is a precursor to future health problems. This study aimed to develop a unique circulating biomarker that could contribute to the diagnosis of male infertility. MATERIALS AND METHODS: The study included 114 adult male participants aged 20-50 years who underwent sperm collection for in vitro fertilization and embryo transfer at Nagoya University Hospital, Gifu University Hospital, and Misao Ladies Hospital. RESULTS: Circulating VEGF-A and sFlt-1 levels did not differ significantly between men with normal and abnormal semen parameters. In contrast, proteomic analysis identified VEGFR1/2-related proteins associated with sperm motility, among which soluble MCAM/CD146 was significantly elevated in participants with abnormal semen parameters (84.0 [20.9-183.8] pg/mL vs 352.7 [115.8-1236.3] pg/mL, p<0.0001), and in similar those with reduced sperm motility (106.5 [25.1-282.6] pg/mL vs 352.7 [125.5-1133.4] pg/mL, p<0.0001). Receiver operating characteristic analysis demonstrated the diagnostic potential of soluble MCAM/CD146, with an area under the curve of 0.787, 66.7% sensitivity, and 78.6% specificity at the optimal threshold, supporting its role as a candidate biomarker for male infertility. CONCLUSIONS: Circulating soluble MCAM/CD146 may represent a potential biomarker associated with abnormal semen parameters.