Preliminary study for predictive indicators focused on semen analysis of inflammation for male infertility
Introduction: Male-infertility-associated factor is found in 50% of couples with infertility, and usually together with abnormal semen parameters. Spermatogenic dysfunction accounts for 82.4% of male infertility. In 30-40% of cases, male-associated factor is not found to explain the underlying impairment of semen parameters were referred to as idiopathic spermatogenic dysfunction. Semen analysis plays the most important role in routine evaluation of idiopathic spermatogenic dysfunction. Recent reports showed a relationship between impairment of semen parameters and inflammatory changes via various cytokines, assessment of inflammatory changes may be a predictive indicator for impairment of semen parameters. Therefore, we investigated the correlation between semen parameters and inflammatory analysis of semen using proteome assay, and extracted predictive indicators focused on semen inflammation for male infertility in this study. Materials and Methods: Eighty-nine couples were enrolled at the Miyake Clinic (Okayama, Japan). Semen analysis findings (seminal volume, concentration, motility rate, and malformation rate) and patient’s (male) age, partner’s (female) age, height, weight, and body mass index (BMI) were obtained from the medical information. The mean sperm concentration (SD) was 83.57 (64.77) × 106/mL, mean sperm motility rate (SD) was 37.82% (16.50%) in 89 patients. From the results of the semen analysis, four patients with the highest sperm motility rate were classified as normal sperm motility group, and four patients with the lowest sperm motility rate were classified as low sperm motility group. Four patients with the highest sperm concentration were classified as normal sperm concentration group, and four patients with the lowest sperm concentration were classified as low sperm concentration group. Proteome assay was performed on 16 patients from the four groups. Quantitative assay of extracted indicators from the proteome assay were performed in 89 patients to investigate the validation of predictive indicators for male infertility in the semen using enzyme-linked immunosorbent assay (ELISA) methods. Results: From the results of the proteome assay, Growth differentiation factor-15 (GDF-15), Kallikrein 3 (KLK3) and Trefoli factor 3 (TFF3) were extracted as indicators related to male infertility. Quantitative assay showed a negative correlation between GDF-15, KLK3 and sperm motility. TFF3 negatively correlated not only with sperm motility but also with sperm concentration and malformation. Conclusions: Extracted three indicators (GDF-15, KLK3 and TFF3) in the semen containing sperm showed statistically significant difference with semen parameters, and negative correlation with semen parameters (sperm motility, concentration and malformation). GDF-15, KLK3 and TFF3 levels in the semen containing sperm may be novel predictive indicators focused on semen analysis of inflammation for male infertility.