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NRF2 Plays a Critical Role in Both Self and EGCG Protection against Diabetic Testicular Damage
Chenyu Pan1, Shengzhu Zhou1, Junduo Wu2
1Department of Anesthesiology, The Second Hospital of Jilin University, 218 Ziqiang St., Changchun, Jilin 130041, China.
Abstract:
Activation of nuclear factor erythroid 2-related factor 2 (NRF2) has been found to ameliorate diabetic testicular damage (DTD) in rodents. However, it was unclear whether NRF2 is required for these approaches in DTD. Epigallocatechin gallate (EGCG) is a potent activator of NRF2 and has shown beneficial effects on multiple diabetic complications. However, the effect of EGCG has not been studied in DTD. The present study aims to explore the role of NRF2 in both self and EGCG protection against DTD. Therefore, streptozotocin-induced diabetic C57BL/6 wild type (WT) and Nrf2 knockout (KO) mice were treated in the presence or absence of EGCG, for 24 weeks. The Nrf2 KO mice exhibited more significant diabetes-induced loss in testicular weight and spermatozoa count, and increase in testicular apoptotic cell death, as compared with the WT mice. EGCG activated NRF2 expression and function, preserved testicular weight and spermatozoa count, and attenuated testicular apoptotic cell death, endoplasmic reticulum stress, inflammation, and oxidative damage in the WT diabetic mice, but not the Nrf2 KO diabetic mice. The present study demonstrated for the first time that NRF2 plays a critical role in both self and EGCG protection against DTD.
Insights
Nuclear factor erythroid 2-related factor 2 (NRF2) is crucial for protecting against diabetic testicular damage (DTD). Activating NRF2, either naturally or with epigallocatechin gallate (EGCG), preserves testicular health in diabetic mice.
Area of Science:
- Reproductive Biology
- Endocrinology
- Diabetology
Background:
- Diabetic testicular damage (DTD) is a significant complication of diabetes.
- Nuclear factor erythroid 2-related factor 2 (NRF2) activation shows promise in mitigating DTD.
- The specific role of NRF2 in DTD and its response to NRF2-activating compounds like EGCG remains unclear.
Purpose of the Study:
- To investigate the essential role of NRF2 in protecting against DTD.
- To determine if epigallocatechin gallate (EGCG) exerts its protective effects against DTD via NRF2 activation.
- To compare the protective effects of NRF2 activation with and without EGCG treatment in a mouse model of diabetes.
Main Methods:
- Streptozotocin-induced diabetic wild-type (WT) and Nrf2 knockout (KO) mice were used.
- Mice were treated with or without epigallocatechin gallate (EGCG) for 24 weeks.
- Evaluated outcomes included testicular weight, sperm count, apoptosis, endoplasmic reticulum stress, inflammation, and oxidative damage.
Main Results:
- Nrf2 KO diabetic mice showed exacerbated testicular damage compared to WT diabetic mice.
- EGCG treatment preserved testicular weight and sperm count in WT diabetic mice.
- EGCG attenuated apoptosis, endoplasmic reticulum stress, inflammation, and oxidative damage in WT diabetic mice, but not in Nrf2 KO diabetic mice.
Conclusions:
- NRF2 is critical for both endogenous and EGCG-mediated protection against diabetic testicular damage.
- EGCG's protective effects against DTD are dependent on NRF2 activation.
- Targeting NRF2 pathways may represent a therapeutic strategy for managing DTD.
