Omolaoye Temidayo S, Du Plessis Stefan S
Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Drive, Tygerberg, 7505 South Africa.
Department of Basic Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.
Toxicol Res. 2020 Apr 24;37(1):35-46. doi: 10.1007/s43188-020-00040-7. eCollection 2021 Jan.
This study was designed to (1) investigate the possible mechanisms through which diabetes-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) activation can affect male reproductive function; and (2) corroborate the interaction of previously established independent pathways. Male albino Wistar rats (14-weeks old) weighing 250-300 g received either a single intraperitoneal injection of streptozotocin (30 mg/kg or 60 mg/kg), represented as STZ30 or STZ60 respectively, or citrate buffer (control). Diabetes mellitus (DM) was confirmed if plasma glucose levels were ≥ 14 mmol/L after 1 week. Animals were sacrificed after 8 weeks of treatment by an overdose of sodium pentobarbital (160 mg/kg body weight). The testes and epididymides were harvested. The testes were used for biochemical and Western blot analysis, while sperm was retrieved from the epididymis and analysed with computer-aided sperm analysis. The blood glucose levels of STZ60 animals were above the cut-off point and hence these animals were regarded as diabetic. Diabetic animals presented with a non-significant increase in AGE and RAGE expression. Diabetic animals showed a significant increase in the expression of cleaved caspase 3 compared to control ( < 0.001), and these animals also presented with an increase in the expression of JNK ( < 0.05), PARP ( = 0.059) and p38 MAPK ( = 0.1). Diabetic animals also displayed decreased catalase activity accompanied by a non-significant increase in malondialdehyde levels. Additionally, there was a significant decrease in the percentage of progressively motile spermatozoa ( < 0.05) in diabetic animals. This study has shed some light on the interplay between DM, AGE, RAGE and mitogen-activated protein kinase signalling in the testes of diabetic rats, which can result in altered sperm function and contribute to male infertility. However, more studies are needed to better understand this complicated process.
（1）探究糖尿病诱导的晚期糖基化终末产物（AGEs）和AGE受体（RAGE）激活可能影响雄性生殖功能的机制；（2）证实先前确立的独立通路之间的相互作用。体重250 - 300克的14周龄雄性白化Wistar大鼠，分别接受单次腹腔注射链脲佐菌素（30毫克/千克或60毫克/千克），分别表示为STZ30或STZ60，或柠檬酸盐缓冲液（对照）。如果1周后血浆葡萄糖水平≥14毫摩尔/升，则确诊为糖尿病（DM）。治疗8周后，通过过量注射戊巴比妥钠（160毫克/千克体重）处死动物。采集睾丸和附睾。睾丸用于生化和蛋白质印迹分析，而精子从附睾中取出并用计算机辅助精子分析进行分析。STZ60组动物的血糖水平高于临界值，因此这些动物被视为糖尿病动物。糖尿病动物的AGE和RAGE表达有不显著增加。与对照组相比，糖尿病动物的裂解型半胱天冬酶3表达显著增加（<0.001），并且这些动物的JNK表达也增加（<0.05）、PARP表达增加（=0.059）和p38丝裂原活化蛋白激酶表达增加（=0.1）。糖尿病动物还表现出过氧化氢酶活性降低，同时丙二醛水平有不显著增加。此外，糖尿病动物中进行性运动精子的百分比显著降低（<0.05）。本研究揭示了糖尿病大鼠睾丸中糖尿病、AGE、RAGE和丝裂原活化蛋白激酶信号之间的相互作用机制，这可能导致精子功能改变并导致男性不育。然而，需要更多研究来更好地理解这一复杂过程。
