Decreased expressions of calcium- and integrin-binding protein 4 in the testes of patients with azoosperma and in the ejaculated spermatozoa of patients with abnormal semen parameters.

Objective: Oligoasthenozoospermia (OAZS), asthenozoospermia (AZS), and azoospermia are the major causes of male infertility with no effective therapeutic treatment. To determine the expression and distribution of calcium- and integrin-binding protein 4 (CIB4) in the patients with azoospermia and OAZS, it is important to explore novel targets and treatment strategies for patients with abnormal semen parameters.

Design: A small piece of testicular tissue was obtained by multi-site testicular biopsy from each of a total of 16 patients with azoospermia revealed in two groups, i.e., nonobstructive azoospermia (NOA; n = 8) and obstructive azoospermia (OA; n = 8). Sperm samples were collected from 24 infertile men categorized in two groups, OAZS (n = 11) and AZS (n = 13). The control group contained a total of 20 fertile men. Computer-assisted semen analysis (CASA) was performed to assess the sperm motility. Quantitative real-time PCR (RT-qPCR) and Western blot analyses were performed to examine the expression of CIB4.

Results: The results of RT-qPCR and Western blotting analyses revealed the decreased expression levels of CIB4 mRNA and CIB4 protein in both the sperm of the OAZS patients and the testis tissue of NOA patients. The results of linear regression analysis of CIB4 mRNA expression with the clinical features of participants showed that the CIB4 mRNA level was positively correlated with sperm progressive motility (r = 0.397, P < 0.01) and sperm viability (r = 0.364, P < 0.05).

Conclusions: We conclude that decreased expression level of CIB4 in human testis and sperm, may be a contributor or a downstream indicator for some cases of azoospermia, especially OA and OAZS. The high expression level of CIB4 mRNA in patients with normal semen parameters suggests that CIB4 in human-ejaculated spermatozoa would potentially contribute to the diagnosis and treatment of male infertility caused by deficient sperm motility and count. These results provide novel insights into the molecular mechanisms underlying the male infertility and the clinical importance of CIB4 in the treatment of infertility.