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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
MAPK immunoreactivity in streptozotocin-induced diabetic rat testis
Yelız Bozdemır Donmez1, Gulnur Kizilay2, Yeter Topcu-Tarladacalisir2
1Department of Histology and Embryology, Faculty of Medicine, Namık Kemal University, Tekirdag, Turkey.
Purpose:
To evaluate the alterations of two mitogen-activated protein kinases (MAPK)s, extracellular signal regulated kinase (ERK) and c-Jun NH2 terminal kinase (JNK), in the testes of male rats with experimental diabetes.
Methods:
Twenty males Sprague-Dawley rats were randomly divided into a control group (n=8) and a diabetes group (administration of 40 mg/kg/day streptozotocin (STZ) for five sequential days, n=12). After six weeks, testicular biopsy samples were obtained for light microscopy and immunohistochemical methods.
Results:
The PCNA (proliferating cell nuclear antigen) index was significantly decreased in the diabetes group (p=0.004) when compared to the control group. Both total (t)-ERK and phosphor (p)-ERK immunoreactivities were significantly decreased in the diabetes group (p=0.004, p<0.001, respectively). The t-JNK immunoreactivity was unchanged in both groups (p=0.125), while p-JNK immunoreactivity was significantly increased in the diabetic group (p=0.002).
Conclusions:
The decrease of androgen levels in the course of diabetes may contribute to the decrease of the immunoreactivities of t-ERK and p-ERK. JNK may be activated due to the changes in various cytokines and chemochines that participate in the oxidative stress process of diabetes. Therefore, testicular apoptosis may occur and lead to infertility associated with diabetes.
Insights
Experimental diabetes in male rats significantly alters testicular cell proliferation and key signaling pathways. Diabetic rats showed decreased extracellular signal-regulated kinase (ERK) and increased c-Jun NH2-terminal kinase (JNK) activity, suggesting a role in diabetes-induced infertility.
Area of Science:
- Endocrinology
- Molecular Biology
- Reproductive Science
Background:
- Diabetes mellitus is a complex metabolic disorder with known adverse effects on male reproductive function.
- Mitogen-activated protein kinases (MAPKs) play crucial roles in cellular processes, including proliferation, differentiation, and apoptosis, within the testes.
Purpose of the Study:
- To investigate the impact of experimental diabetes on the expression and activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) in male rat testes.
- To assess the relationship between diabetes-induced alterations in these MAPK pathways and testicular cell proliferation.
Main Methods:
- Male Sprague-Dawley rats were induced with experimental diabetes using streptozotocin (STZ).
- Testicular tissue samples were collected after six weeks for light microscopy and immunohistochemical analysis.
- Proliferating cell nuclear antigen (PCNA) index, total (t)-ERK, phosphor (p)-ERK, total (t)-JNK, and phosphor (p)-JNK immunoreactivities were quantified.
Main Results:
- Diabetic rats exhibited a significant reduction in the PCNA index, indicating decreased cell proliferation.
- Immunoreactivity for both total ERK (t-ERK) and phosphorylated ERK (p-ERK) was significantly decreased in diabetic testes.
- While total JNK (t-JNK) levels remained unchanged, phosphorylated JNK (p-JNK) immunoreactivity was significantly elevated in diabetic rats.
Conclusions:
- The observed decrease in t-ERK and p-ERK may be linked to reduced androgen levels in diabetic conditions.
- Increased p-JNK suggests activation of the JNK pathway, potentially due to oxidative stress and inflammatory mediators associated with diabetes.
- These MAPK pathway alterations may contribute to testicular apoptosis and subsequent infertility in diabetic males.

