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Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats

BACKGROUND: Diabetes mellitus (DM), a chronic metabolic disease, severely impairs male reproductive function. However, the underpinning mechanisms are still incompletely defined, and there are no effective strategies or medicines for these reproductive lesions. Icariin (ICA), the main active compone...

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Autores principales: He, Weiguo, Liu, Huiqing, Hu, Linlin, Wang, Yaohui, Huang, Lane, Liang, Aihong, Wang, Xuan, Zhang, Qing, Chen, Yi, Cao, Yi, Li, Suyun, Wang, Junli, Lei, Xiaocan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576896/
https://www.ncbi.nlm.nih.gov/pubmed/34753504
http://dx.doi.org/10.1186/s12958-021-00851-9
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author He, Weiguo
Liu, Huiqing
Hu, Linlin
Wang, Yaohui
Huang, Lane
Liang, Aihong
Wang, Xuan
Zhang, Qing
Chen, Yi
Cao, Yi
Li, Suyun
Wang, Junli
Lei, Xiaocan
author_facet He, Weiguo
Liu, Huiqing
Hu, Linlin
Wang, Yaohui
Huang, Lane
Liang, Aihong
Wang, Xuan
Zhang, Qing
Chen, Yi
Cao, Yi
Li, Suyun
Wang, Junli
Lei, Xiaocan
author_sort He, Weiguo
collection PubMed
description BACKGROUND: Diabetes mellitus (DM), a chronic metabolic disease, severely impairs male reproductive function. However, the underpinning mechanisms are still incompletely defined, and there are no effective strategies or medicines for these reproductive lesions. Icariin (ICA), the main active component extracted from Herba epimedii, is a flavonoid traditionally used to treat testicular dysfunction. Whether ICA can improve male reproductive dysfunction caused by DM and its underlying mechanisms are still unclear. In this study, by employing metformin as a comparative group, we evaluated the protective effects of ICA on male reproductive damages caused by DM and explored the possible mechanisms. METHODS: Rats were fed with a high fat diet (HFD) and then intraperitoneally injected with streptozotocin (STZ) to induce diabetes. Diabetic rats were randomly divided into T2DM + saline group, T2DM + metformin group and T2DM + ICA group. Rats without the treatment of HFD and STZ were used as control group. The morphology of testicular tissues was examined by histological staining. The mRNA expression levels were determined by quantitative real-time PCR. Immunostaining detected the protein levels of proliferating cell nuclear antigen (PCNA), hypoxia-inducible factor 1-alpha (HIF-1α) and sirtuin 1 (SIRT1) in testicular tissues. TUNEL assay was performed to determine cell apoptosis in the testicular tissues. The protein expression levels of HIF-1α and SIRT1 in the testicular tissues were determined by western blot assay. RESULTS: ICA effectively improved male reproductive dysfunction of diabetic rats. ICA administration significantly decreased fasting blood glucose (FBG) and insulin resistance index (IRI). In addition, ICA increased testis weight, epididymis weight, sperm number, sperm motility and the cross-sectional area of seminiferous tubule. ICA recovered the number of spermatogonia, primary spermatocytes and Sertoli cells. Furthermore, ICA upregulated the expression of PCNA, activated SRIT1-HIF-1α signaling pathway, and inhibited intrinsic mitochondria dependent apoptosis pathway by upregulating the expression of Bcl-2 and downregulating the expression of Bax and caspase 3. CONCLUSION: These results suggest that ICA could attenuate male reproductive dysfunction of diabetic rats possibly via increasing cell proliferation and decreasing cell apoptosis of testis. ICA potentially represents a novel therapeutic strategy against DM-induced testicular damages.
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spelling pubmed-85768962021-11-10 Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats He, Weiguo Liu, Huiqing Hu, Linlin Wang, Yaohui Huang, Lane Liang, Aihong Wang, Xuan Zhang, Qing Chen, Yi Cao, Yi Li, Suyun Wang, Junli Lei, Xiaocan Reprod Biol Endocrinol Research BACKGROUND: Diabetes mellitus (DM), a chronic metabolic disease, severely impairs male reproductive function. However, the underpinning mechanisms are still incompletely defined, and there are no effective strategies or medicines for these reproductive lesions. Icariin (ICA), the main active component extracted from Herba epimedii, is a flavonoid traditionally used to treat testicular dysfunction. Whether ICA can improve male reproductive dysfunction caused by DM and its underlying mechanisms are still unclear. In this study, by employing metformin as a comparative group, we evaluated the protective effects of ICA on male reproductive damages caused by DM and explored the possible mechanisms. METHODS: Rats were fed with a high fat diet (HFD) and then intraperitoneally injected with streptozotocin (STZ) to induce diabetes. Diabetic rats were randomly divided into T2DM + saline group, T2DM + metformin group and T2DM + ICA group. Rats without the treatment of HFD and STZ were used as control group. The morphology of testicular tissues was examined by histological staining. The mRNA expression levels were determined by quantitative real-time PCR. Immunostaining detected the protein levels of proliferating cell nuclear antigen (PCNA), hypoxia-inducible factor 1-alpha (HIF-1α) and sirtuin 1 (SIRT1) in testicular tissues. TUNEL assay was performed to determine cell apoptosis in the testicular tissues. The protein expression levels of HIF-1α and SIRT1 in the testicular tissues were determined by western blot assay. RESULTS: ICA effectively improved male reproductive dysfunction of diabetic rats. ICA administration significantly decreased fasting blood glucose (FBG) and insulin resistance index (IRI). In addition, ICA increased testis weight, epididymis weight, sperm number, sperm motility and the cross-sectional area of seminiferous tubule. ICA recovered the number of spermatogonia, primary spermatocytes and Sertoli cells. Furthermore, ICA upregulated the expression of PCNA, activated SRIT1-HIF-1α signaling pathway, and inhibited intrinsic mitochondria dependent apoptosis pathway by upregulating the expression of Bcl-2 and downregulating the expression of Bax and caspase 3. CONCLUSION: These results suggest that ICA could attenuate male reproductive dysfunction of diabetic rats possibly via increasing cell proliferation and decreasing cell apoptosis of testis. ICA potentially represents a novel therapeutic strategy against DM-induced testicular damages. BioMed Central 2021-11-09 /pmc/articles/PMC8576896/ /pubmed/34753504 http://dx.doi.org/10.1186/s12958-021-00851-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
He, Weiguo
Liu, Huiqing
Hu, Linlin
Wang, Yaohui
Huang, Lane
Liang, Aihong
Wang, Xuan
Zhang, Qing
Chen, Yi
Cao, Yi
Li, Suyun
Wang, Junli
Lei, Xiaocan
Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats
title Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats
title_full Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats
title_fullStr Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats
title_full_unstemmed Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats
title_short Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats
title_sort icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576896/
https://www.ncbi.nlm.nih.gov/pubmed/34753504
http://dx.doi.org/10.1186/s12958-021-00851-9
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