Department of Surgery, Division of Urology, Human Reproduction Section, Universidade Federal de São Paulo - UNIFESP, São Paulo, Brazil.
Department of Basic Sciences, Faculty of Veterinary Medicine, Islamic Azad University, Urmia Branch, Urmia, Iran.
Gene. 2021 Oct 5;799:145847. doi: 10.1016/j.gene.2021.145847. Epub 2021 Jul 15.
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.
Mature male Wistar rats (n = 24) were divided into 3 groups: control, T1D-induced (received 40 mg kg streptozotocin) and insulin-treated T1D (Ins T1D; received 40 mg kg 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.
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.
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.
未经控制的 1 型糖尿病（T1D）会损害男性的生殖潜能。胰岛素治疗可恢复代谢参数，但尚不清楚其如何保护男性生殖健康。在此，我们假设胰岛素治疗 T1D 大鼠可通过介导与细胞凋亡和细胞周期相关的机制来保护睾丸生理学。
将成熟雄性 Wistar 大鼠（n=24）分为 3 组：对照组、T1D 诱导组（给予 40mg/kg 链脲佐菌素）和胰岛素治疗 T1D 组（Ins T1D；给予 40mg/kg 链脲佐菌素，然后用 0.9IU/100gr 胰岛素治疗 56 天）（n=8/组）。通过免疫组织化学（IHC）和 RT-PCR 技术检测睾丸组织中细胞凋亡途径调节剂（Bcl-2、Bax、Caspase-3 和 p53）和细胞周期机制核心调节剂（Cyclin D1、Cdk-4 和 p21）的表达水平。通过 TUNEL 染色评估睾丸细胞凋亡百分比。
我们的数据表明，胰岛素治疗可恢复 T1D 大鼠睾丸中 T1D 诱导的 Caspase-3 和 p53 表达增加（P<0.05）。此外，与 T1D 大鼠的睾丸相比，胰岛素治疗的 T1D 大鼠的睾丸表现出 Cyclin D1 和 cdk-4 的表达增加，以及 p21 的表达减少。最后，胰岛素治疗可相当控制 T1D 诱导的细胞凋亡。因此，胰岛素治疗可使 T1D 大鼠睾丸中的凋亡细胞百分比显著减少（p<0.05）。
胰岛素治疗能够恢复 T1D 引起的睾丸中细胞凋亡和增殖相关基因的网络表达，并通过这种机制维持男性的生育能力。
