The Effect of Chlorogenic Acid on Endoplasmic Reticulum Stress and Steroidogenesis in the Testes of Diabetic Rats: Study of mRNA Expressions of GRP78, XBP1s, 3β-HSD, and 17β-HSD

Abstract

Diabetes mellitus (DM) is a chronic endocrine metabolic disorder that can increase the incidence of infertility. Excessive production of reactive oxygen species (ROS) can trigger oxidative stress reactions and reduce antioxidant content. The increase of ROS can exert an impact on the endoplasmic reticulum (ER) stress conditions and inhibit the steroidogenesis of the testes. The objectives of the current study were to determine the effect of chlorogenic acid (CGA) as an antioxidant in reducing ER stress conditions (mRNA expressions of GRP78, XBP1s), and to increase steroidogenesis (mRNA expressions of 3β-HSD and 17β-HSD) in the testis of DM rats. A total of 24 rats were randomly divided into six groups, namely: control group, DM1.5 months, DM2 months, and DM group were treated with CGA with three different doses (12.5 mg/kgBW, 25 mg/kgBW, and 50 mg/kgBW), respectively. Testicular tissue was isolated for examination of GRP78, XBP1s, 3β-HSD, and 17β-HSD mRNA expressions using RT-PCR. In the CGA1 group, GRP78 mRNA expression level was lower than in the DM2 group and was statistically different (p=0.021). XBP1s mRNA expression in the CGA1 group was lower and significantly different when compared to the DM2 group (p=0.018). The mRNA expression of 3β -HSD in the CGA1 group was higher than that in the DM1.5 and DM2 groups, which were statistically significant with p=0.000 and p=0,008. The comparison of 17β - HSD mRNA expression in the CGA1 group was higher than the DM1,5 and DM2 groups with p=0.013 and p=0.012. Administration of CGA at a dose of 12.5 mg/kgBW can reduce ER stress conditions and increase testicular steroidogenesis in DM rat models. These results were seen based on low GRP78 and XBP1s mRNA expressions, and high 3β-HSD and 17β-HSD mRNA expressions after CGA administration.