Background: Uncontrolled type 1 diabetes mellitus (T1D) impairs reproductive potential of males. Insulin treatment restores metabolic parameters but it is unclear how it protects male reproductive health. Herein, we hypothesized that insulin treatment to T1D rats protects testicular physiology by mediating mechanisms associated with apoptosis and cell cycle.
Methods: Mature male Wistar rats (n = 24) were divided into 3 groups: control, T1D-induced (received 40 mg kg-1 streptozotocin) and insulin-treated T1D (Ins T1D; received 40 mg kg-1 streptozotocin and then treated 0.9 IU/100 gr of insulin for 56 days) (N = 8/group). Expression levels of intrinsic apoptosis pathways regulators (Bcl-2, Bax, Caspase-3 and p53) and core regulators of cell cycle machinery (Cyclin D1, Cdk-4 and p21) were determined in testicular tissue by immunohistochemistry (IHC) and RT-PCR techniques. The percentage of testicular apoptotic cells was evaluated by TUNEL staining.
Results: Our data shows that insulin treatment to T1D rats restored (P < 0.05) T1D-induced increased of caspase-3 and p53 expression in testis. Moreover, the testis of T1D rats treated with insulin exhibited increased expression of Cyclin D1 and cdk-4, and a reduced expression of p21 when compared with the expression in testis of T1D rats. Finally, insulin treatment could fairly control T1D-induced apoptosis. Accordingly, treatment of T1D rats with insulin led to a remarkable reduction (p < 0.05) in the percentage of apoptotic cells in the testis.
Conclusions: Insulin treatment is able to restore the network expression of apoptosis and proliferation-related genes caused by T1D in the testis and via this mechanism, preserve the fertility of males.
Keywords: Apoptosis; Cell cycle; Diabetes; Spermatogenesis; Streptozotocin.
Copyright © 2021 Elsevier B.V. All rights reserved.