OCTN2 expression and function in the Sertoli cells of testes from patients with non-obstructive azoospermia

Background

Among couples, male factors account for approximately 50% of infertility cases, with nonobstructive azoospermia (NOA) representing one of the most clinically common and severe categories of male infertility, affecting approximately 10–15% of patients. Currently, L-carnitine is clinically used to improve spermatogenesis by regulating Sertoli cell function. Multiple clinical trials have described the efficacy of L-carnitine in treating NOA. Notably, Sertoli cells rely on organic carnitine transporter 2 (OCTN2) for carnitine transport. However, it remains unknown whether OCTN2 expression is involved in the pathological process of NOA.

Objective

To investigate the expression and function of OCTN2 in Sertoli cells from patients with NOA.

Materials and methods

Ten testicular tissue samples were collected, including five from a healthy group and five from a group of patients with NOA. Immunohistochemistry and immunofluorescence were used to detect the expression of OCTN2 in testicular tissue. Additionally, an Octn2-KO TM4 cell line (a mouse testicular Sertoli cell line) was constructed to explore the function of OCTN2 expression in Sertoli cells through transcriptomic sequencing, cell proliferation experiments, metabolomic analysis, and Western blot analysis.

Results

Compared with those of the healthy group, the immunohistochemistry results revealed a significant decrease in OCTN2 expression in the Sertoli cells of the NOA group. Further investigation through cell proliferation experiments revealed a reduction in the proliferative capacity of the Octn2-KO TM4 cell line. Transcriptomic sequencing and metabolomic data analysis revealed a decrease in autophagy in the Octn2-KO TM4 cell line. Western blot analysis subsequently verified the expression levels of autophagy-related proteins.

Conclusion

In the Sertoli cells of NOA patients, decreased OCTN2 protein expression leads to decreased cell proliferation and autophagy abnormalities, which may play a crucial role in the spermatogenic dysfunction observed in NOA patients.