Protective effects of &lt;i&gt;Lycium barbarum&lt;/i&gt; polysaccharide on male sexual dysfunction and fertility impairments by activating hypothalamic pituitary gonadal axis in streptozotocin-induced type-1 diabetic male mice

Shi, Guangjiang; Zheng, Jie; Wu, Jing; Qiao, Hai-Qi; Chang, Qing; Niu, Yang; Sun, Tao; Li, Yuxiang; Yu, Jian‐Qiang

doi:10.1507/endocrj.ej16-0430

Cited by 49 publications

(41 citation statements)

References 46 publications

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“…The decrease in mating and fertility indexes in DC group has a direct link with testosterone level. Both human (Hackett et al ., ) and experimental (Shi et al ., ; Yang et al ., ) studies have reported decreased testosterone level and suppressed sexual function in diabetic state. Testosterone replacement therapy in diabetic males significantly improves sexual appetite and erectile function (Hackett et al ., , ), thus suggesting the importance of testosterone in male fertility.…”

Section: Discussionmentioning

confidence: 99%

Down‐regulation of steroidogenesis‐related genes and its accompanying fertility decline in streptozotocin‐induced diabetic male rats: ameliorative effect of metformin

et al. 2018

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Background: Metformin has long been used for glycemic control in diabetic state. Recently, other benefits of metformin beyond blood glucose regulation have emerged. Objectives: To investigate the effect of metformin on the expression of testicular steroidogenesis-related genes, spermatogenesis, and fertility of male diabetic rats. Materials and methods: Eighteen adult male Sprague Dawley rats were divided into three groups, namely normal control (NC), diabetic control (DC), and metformin-treated (300 mg/kg body weight/day) diabetic rats (D+Met). Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.), followed by oral treatment with metformin for four weeks. Results: Diabetes decreased serum and intratesticular testosterone levels and increased serum but not intratesticular levels of luteinizing hormone. Sperm count, motility, viability, and normal morphology were decreased, while sperm nuclear DNA fragmentation was increased in DC group, relative to NC group. Testicular mRNA levels of androgen receptor, luteinizing hormone receptor, cytochrome P450 enzyme (CYP11A1), steroidogenic acute regulatory (StAR) protein, 3b-hydroxysteroid dehydrogenase (HSD), and 17b-HSD, as well as the level of StAR protein and activities of CYP11A1, 3b-HSD, and 17b-HSD, were decreased in DC group. Similarly, decreased activities of epididymal antioxidant enzymes and increased lipid peroxidation were observed in DC group. Consequently, decreased litter size, fetal weight, mating and fertility indices, and increased pre-and post-implantation losses were recorded in DC group. Following intervention with metformin, we observed increases in serum and intratesticular testosterone levels, Leydig cell count, improved sperm parameters, and decreased sperm nuclear DNA fragmentation. Furthermore, mRNA levels and activities of steroidogenesis-related enzymes were increased, with improved fertility outcome. Discussion and conclusion: Diabetes mellitus is associated with dysregulation of steroidogenesis, abnormal spermatogenesis, and fertility decline. Controlling hyperglycemia is therefore crucial in preserving male reproductive function. Metformin not only regulates blood glucose level, but also preserves male fertility in diabetic state. Research has shown that DM impairs several aspects of the male reproductive function (Nna et al., 2017a). Decreased daily sperm production, sperm count, motility and viability, increased 110

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Section: Discussionmentioning

confidence: 99%

Down‐regulation of steroidogenesis‐related genes and its accompanying fertility decline in streptozotocin‐induced diabetic male rats: ameliorative effect of metformin

et al. 2018

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“…Furthermore, the decreased fertility outcome in DC group is indicative of poor spermatozoa quality and is consistent with previous studies. 8,58 In fact, studies have demonstrated that sperm DNA fragmentation is a major contributor to spontaneous miscarriages. 49,59 The significant positive associations between pre-and post-implantation losses, with sperm nDNA fragmentation in the present study further confirms the fact that spermatozoa health not only determines whether fertilization will be successful or not, but also determines (in part) the survival of pregnancies after successful implantation.…”

Section: Discussionmentioning

confidence: 99%

Malaysian propolis and metformin mitigate subfertility in streptozotocin‐induced diabetic male rats by targeting steroidogenesis, testicular lactate transport, spermatogenesis and mating behaviour

et al. 2019

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Background: Diabetes mellitus is one of the risk factors for male subfertility/infertility. Malaysian propolis is reported to decrease hyperglycaemia in diabetic state. Objectives:The present study investigated the protective effect of Malaysian propolis on diabetes-induced subfertility/infertility. Additionally, its combined beneficial effects with metformin were investigated. Materials and methods:Forty adult male Sprague Dawley rats were randomly assigned into five groups, namely normal control, diabetic control, diabetic + Malaysian propolis (300 mg/k.g. b.w.), diabetic + metformin (300 mg/kg b.w.) and diabetic + Malaysian propolis + metformin. Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.) and treatment lasted for 4 weeks. During the 4thweek, mating behavioural experiments were performed using sexually receptive female rats. Thereafter, fertility parameters were assessed in the female rats. Results: Malaysian propolis increased serum and intratesticular free testosterone levels, up-regulated the mRNA levels of AR and luteinizing hormone receptor, upregulated the mRNA and protein levels of StAR, CYP11A1, CYP17A1, 3β-HSD and 17β-HSD in the testes of diabetic rats. Furthermore, Malaysian propolis up-regulated testicular MCT2, MCT4 and lactate dehydrogenase type C mRNA levels, in addition to improving sperm parameters (count, motility, viability and normal morphology) and decreasing sperm nDNA fragmentation in diabetic rats. Malaysian propolis improved mating behaviour by increasing penile guanosine monophosphate levels. Malaysian propolis also improved fertility outcome as seen with decreases in pre-and postimplantation losses, increases in gravid uterine weight, litter size per dam and foetal weight. Malaysian propolis's effects were comparable to metformin. However, their combination yielded better results relative to the monotherapeutic interventions. Conclusion: Malaysian propolis improves fertility potential in diabetic state by targeting steroidogenesis, testicular lactate metabolism, spermatogenesis and mating

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“…Shi et al showed that LBP could exert protective effects on DM-induced spermatogenic dysfunction by increasing antioxidative enzyme activities and inhibiting cell death (19). In addition, LBP could exert functional recovery of male sexual dysfunction and fertility damage induced by DM in male mice by regulating the hypothalamus-pituitary-gonadal axis endocrine activity (20). However, detailed investigation into the molecular mechanisms underlying LBP-mediated protective effects on male reproductive dysfunction induced by DM is required.…”

Section: Introductionmentioning

confidence: 99%

Lycium barbarum Polysaccharides Improve Testicular Spermatogenic Function in Streptozotocin-Induced Diabetic Rats

et al. 2020

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The objective of this study was to investigate the protective effects of Lycium barbarum polysaccharides (LBP) on testicular spermatogenic function in streptozotocin (STZ)-induced diabetic rats. Compared to the control group, blood glucose levels were significantly increased and the insulin resistance was markedly aggravated in STZ-induced diabetic rats. Further, the weight of testis and epididymis and the sperm number and motility were decreased in diabetic rats. Pathological changes were also observed in the spermatogenic tubules, along with a decreased number of spermatogenic cells, downregulated proliferating cell nuclear antigen (PCNA) expression, and increased cell apoptosis in the testes. Compared to the saline-treated diabetic rat group, metformin and LBP treatment significantly decreased the level of blood glucose and improved insulin resistance and testicular function. After treatment with metformin and LBP, the pathological changes in the spermatogenic tubules improved significantly, with an increase in the number of spermatogenic cells, upregulation of PCNA, and suppression of apoptosis in the testes. The expressions of sirtuin 1 (SIRT1) and hypoxia-inducible factor 1-alpha (HIF-1α) in diabetic testes were also upregulated by metformin or LBP treatment. In summary, LBP exerted protective effects by increasing cell proliferation, inhibiting cell apoptosis, and regulating SIRT1/HIF-1α expression in the testes of diabetic rats.

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Protective effects of <i>Lycium barbarum</i> polysaccharide on male sexual dysfunction and fertility impairments by activating hypothalamic pituitary gonadal axis in streptozotocin-induced type-1 diabetic male mice

Cited by 49 publications

References 46 publications

Down‐regulation of steroidogenesis‐related genes and its accompanying fertility decline in streptozotocin‐induced diabetic male rats: ameliorative effect of metformin

Down‐regulation of steroidogenesis‐related genes and its accompanying fertility decline in streptozotocin‐induced diabetic male rats: ameliorative effect of metformin

Malaysian propolis and metformin mitigate subfertility in streptozotocin‐induced diabetic male rats by targeting steroidogenesis, testicular lactate transport, spermatogenesis and mating behaviour

Lycium barbarum Polysaccharides Improve Testicular Spermatogenic Function in Streptozotocin-Induced Diabetic Rats

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