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

Abstract 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...

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Autores principales:	Weiguo He, Huiqing Liu, Linlin Hu, Yaohui Wang, Lane Huang, Aihong Liang, Xuan Wang, Qing Zhang, Yi Chen, Yi Cao, Suyun Li, Junli Wang, Xiaocan Lei
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Icariin Reproductive protection Spermatogenesis Proliferation Apoptosis Gynecology and obstetrics RG1-991 Reproduction QH471-489
Acceso en línea:	https://doaj.org/article/dd65a757adca461b877e13df5c7d06ba
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spelling	oai:doaj.org-article:dd65a757adca461b877e13df5c7d06ba2021-11-14T12:38:29ZIcariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats10.1186/s12958-021-00851-91477-7827https://doaj.org/article/dd65a757adca461b877e13df5c7d06ba2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12958-021-00851-9https://doaj.org/toc/1477-7827Abstract 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.Weiguo HeHuiqing LiuLinlin HuYaohui WangLane HuangAihong LiangXuan WangQing ZhangYi ChenYi CaoSuyun LiJunli WangXiaocan LeiBMCarticleIcariinReproductive protectionSpermatogenesisProliferationApoptosisGynecology and obstetricsRG1-991ReproductionQH471-489ENReproductive Biology and Endocrinology, Vol 19, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Icariin Reproductive protection Spermatogenesis Proliferation Apoptosis Gynecology and obstetrics RG1-991 Reproduction QH471-489
spellingShingle	Icariin Reproductive protection Spermatogenesis Proliferation Apoptosis Gynecology and obstetrics RG1-991 Reproduction QH471-489 Weiguo He Huiqing Liu Linlin Hu Yaohui Wang Lane Huang Aihong Liang Xuan Wang Qing Zhang Yi Chen Yi Cao Suyun Li Junli Wang Xiaocan Lei Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats
description	Abstract 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.
format	article
author	Weiguo He Huiqing Liu Linlin Hu Yaohui Wang Lane Huang Aihong Liang Xuan Wang Qing Zhang Yi Chen Yi Cao Suyun Li Junli Wang Xiaocan Lei
author_facet	Weiguo He Huiqing Liu Linlin Hu Yaohui Wang Lane Huang Aihong Liang Xuan Wang Qing Zhang Yi Chen Yi Cao Suyun Li Junli Wang Xiaocan Lei
author_sort	Weiguo He
title	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_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_sort	icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats
publisher	BMC
publishDate	2021
url	https://doaj.org/article/dd65a757adca461b877e13df5c7d06ba
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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

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