ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Reproduction
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1555721
Curcumin Promotes Spermatogenesis in Mice with Cryptorchidism by Regulating Testicular Protein O-GlcNAcylation
Provisionally accepted
Zhen Wang1
Fujia Chen1Yun Li1
Liu Chaoying1
Lizhen Wang2Zhen Lu1Li Hu1Longxuan Li1Yue Wang1Jinyang Lin1Yaxuan Yu1Shengjun Sun3Yurong Yang1Zhijian Zhu1
Siqiang Li1*
Enzhong Li1- 1Huanghuai University, Zhumadian, China
- 2Qilu University of Technology, Jinan, Shandong Province, China
- 3Henan Dadeguang Animal Pharmaceuticals Co., Ltd, Pingdingshan, China
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Curcumin has garnered increasing attention in male reproductive research due to its potential anti-infertility properties. This study aimed to explore the protective effects of curcumin on spermatogenesis impairment in mice with cryptorchidism and to elucidate the underlying mechanisms. A total of 56 male Kunming mice aged 10 to 15 days were randomly assigned to different groups, including a control group (BO) and a cryptorchid group with five curcumin treatment groups (CC25, CC50, CC100, CC200, and CC300) receiving varying doses of curcumin (25, 50, 100, 200, and 300 mg/kg, respectively). After five weeks of treatment, evaluations based on organ coefficients, sperm count detection, testicular 2 pathology analysis, and hormone level assessments determined the most effective curcumin dosage. The findings indicated that cryptorchidism had a detrimental impact on reproductive function, evident by decreased testicular coefficient, cessation of sperm production, abnormal testicular tissue morphology, and hormonal imbalances.Curcumin treatment mitigated these abnormalities, with the most significant improvement observed at a dosage of 100 mg/kg, without substantial adverse effects on other organs. Mechanistic studies revealed that cryptorchidism reduced testicular protein O-GlcNAcylation levels, while curcumin supplementation effectively increased this modification in a dose-dependent manner. Molecular docking and UDP-GlcNAc analyses further demonstrated that curcumin restores O-GlcNAcylation homeostasis by inhibiting OGA via high-affinity binding and enhancing OGT activity through substrate accumulation, synergistically rebalancing O-GlcNAcylation dynamics. This study uncovers a novel mechanism by which curcumin facilitates spermatogenesis through the regulation of testicular protein O-GlcNAcylation, providing a significant theoretical foundation for its utilization in male reproductive health.
Keywords: Curcumin, Spermatogenesis, Cryptorchidism, O-GlcNAcylation, Testicular protein
Received: 05 Jan 2025; Accepted: 06 Jun 2025.
Copyright: © 2025 Wang, Chen, Li, Chaoying, Wang, Lu, Hu, Li, Wang, Lin, Yu, Sun, Yang, Zhu, Li and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Siqiang Li, Huanghuai University, Zhumadian, China
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