Joshi Deepanshu, Sarkar Debarshi, Singh Shio Kumar
Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Biochem Biophys Res Commun. 2017 Sep 2;490(4):1346-1354. doi: 10.1016/j.bbrc.2017.07.026. Epub 2017 Jul 6.
Diabetes mellitus (DM) affects male reproductive system and causes infertility. The male reproductive health is largely dependent upon uptake and proper utilization of glucose by testicular cells. Results show involvement of orexin A (OXA) and its receptor (OX1R) in regulation of steroidogenesis and glucose homeostasis in adult mice testis. However, the role of OX1R in regulation of testicular functions during hyperglycemia has not been investigated so far. The present study, therefore, examined the role of OX1R in regulation of steroidogenesis and glucose homeostasis in testis of adult mice during alloxan-induced type 1 DM. A significant decrease was noted in body weight and testis weight in alloxan-treated mice compared to controls. The blood glucose level, however, was markedly increased in treated animals than in controls. Further, serum and intratesticular level of testosterone, activities of testicular steroidogenic enzymes, and expressions of various steroidogenic markers, OX1R, glucose transporter 3 (GLUT3) and Wilms' tumor gene (WT1) were downregulated in treated mice. The level of glucose, activity of lactate dehydrogenase (LDH) and lactate concentration in the testes of diabetic mice were also decreased; a significant increase in the number of testicular apoptotic cells with concomitant increase in the expression of caspase-3 was noted in these mice. Furthermore, DM affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA). Results thus suggest that type 1 DM impairs testicular steroidogenesis and glucose homeostasis through inhibition of OXA/OX1R signaling cascade due to decreased OX1R expression in adult mice, thereby affecting germ cell survival and their proliferation in the testis.
糖尿病（DM）会影响男性生殖系统并导致不育。男性生殖健康在很大程度上依赖于睾丸细胞对葡萄糖的摄取和正确利用。结果显示，食欲素A（OXA）及其受体（OX1R）参与成年小鼠睾丸中类固醇生成和葡萄糖稳态的调节。然而，迄今为止，OX1R在高血糖期间对睾丸功能调节中的作用尚未得到研究。因此，本研究检测了OX1R在四氧嘧啶诱导的1型糖尿病成年小鼠睾丸中对类固醇生成和葡萄糖稳态的调节作用。与对照组相比，四氧嘧啶处理的小鼠体重和睾丸重量显著降低。然而，处理组动物的血糖水平明显高于对照组。此外，处理组小鼠血清和睾丸内睾酮水平、睾丸类固醇生成酶活性以及各种类固醇生成标志物、OX1R、葡萄糖转运蛋白3（GLUT3）和威尔姆斯瘤基因（WT1）的表达均下调。糖尿病小鼠睾丸中的葡萄糖水平、乳酸脱氢酶（LDH）活性和乳酸浓度也降低；在这些小鼠中，睾丸凋亡细胞数量显著增加，同时半胱天冬酶-3的表达也增加。此外，糖尿病影响生殖细胞增殖，增殖细胞核抗原（PCNA）表达降低。因此，结果表明，1型糖尿病通过抑制成年小鼠中OX1R表达，进而抑制OXA/OX1R信号级联反应，损害睾丸类固醇生成和葡萄糖稳态，从而影响睾丸中生精细胞的存活及其增殖。
