ASIAN JOURNAL OF ANDROLOGY
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2023
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IF 2.9
Yang Yi-Ting,Yan Bin,Li Yu-Hua,Guo Li-Na,Wang Wei-Wei,Liu Li-Jie,Yu He-Guo,Diao Hua
Phosphodiesterase (PDE) inhibitors can improve sperm motility in patients with asthenozoospermia. However, the most commonly reported nonselective PDE inhibitor pentoxifylline and PDE5 inhibitor sildenafil have the disadvantages of requiring a high concentration and destroying sperm integrity. We examined the PDE10A inhibitor PF-2545920 to compare its ability to promote sperm motility with that of pentoxifylline and sildenafil . After seminal plasma was discarded, several semen samples were subjected to four treatments (control, PF-2545920, pentoxifylline , and sildenafil ) to evaluate their ability to affect motility, viability, and spontaneous acrosome reactions. Intracellular calcium and adenosine triphosphate (ATP), mitochondrial membrane potential, and penetration through viscous medium were assessed by flow cytometry, luciferase, and hyaluronic acid after treatment with PF-2545920. Statistical analyses were performed using the analysis of variance statistical test. PF-2545920 elevated the percentage of motile spermatozoa compared to the control, pentoxifylline , and sildenafil groups at 10 µmol l −1 ( P < 0.01). It is less toxic to GC-2spd mouse spermatocytes cells and spermatozoa and causes fewer spontaneous acrosomal reactions ( P < 0.05). PF-2545920 also increased mitochondrial membrane potential ( P < 0.001) and altered intracellular calcium ( P < 0.05) in a dose-dependent manner, including increasing sperm hyaluronic acid penetrating ability ( P < 0.05). Therefore, PF-2545920 might be an excellent choice for stimulating the sperm motility .
研究领域:
生殖生物学
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药理学
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男科学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Xinghua Yu,Yujun Zhang,Lingan Zeng,Haiyan Chen,Xuemei Dong,Tianfu Zhang,Ben Zhong Tang,Fei Sun
Asthenozoospermia, a major cause of male infertility characterized by impaired sperm motility, is critically driven by oxidative stress and dysregulated iron metabolism, which directly induce ferroptosis in sperm cells. To address this, a novel nanotheranostic platform utilizing ferritin nanocages to encapsulate vitexin, a natural flavonoid with potent antioxidant properties and unique aggregation-induced emission (AIE) characteristics, is introduced. This ferritin nanocage-loaded vitexin (HFn@VI) system combines the iron-chelating capability of ferritin with vitexin's ability to mitigate oxidative stress, enabling precise dual-targeting of the ferroptotic pathways in spermatogenic cells. In the asthenozoospermia model mice, HFn@VI significantly improves sperm count and kinematic parameters (motility, velocity) without observable systemic toxicity, demonstrating superior therapeutic efficacy. Mechanistic studies reveal that the ferritin component elevates ferritin heavy chain 1(FTH1) levels, sequestering free iron ions and reducing cellular iron overload. Concurrently, vitexin activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, enhancing glutathione peroxidase 4 (GPX4) expression to inhibit lipid peroxidation and ferroptosis. This study pioneers the application of vitexin, a natural product exhibiting AIE characteristics, as a therapeutic agent in reproductive medicine and underscores the potential of dual-target nanomedicines for precise ferroptosis intervention, establishing a new paradigm for treating male infertility through advances in material science.
研究领域:
纳米医学
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生殖医学
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泌尿科学
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分子生物学
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材料科学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Jinhui Dong,Xiaohui Tong,Jing Xu,Min Pan,Lei Wang,Fei Xu,Yajuan Wang,Li Li,Tongsheng Wang
Researches have proposed that obesity might contribute to development of oligoasthenospermia. This study was performed to confirm whether obesity contributes to oligoasthenospermia as well as the underlying mechanisms in mice fed with a high fat diet (HFD). Meanwhile, the actions of metformin, a drug of well-known weight-lowering effect, on sperm quality in obese mice were investigated. Our results showed that HFD feeding reduced sperm quality and steroid hormone levels in mice, associated with disruptions in testicular histomorphology and spermatogenesis. Moreover, obesity increased sperm apoptosis. These effects could be prevented by metformin treatment in HFD-fed mice. Mechanistically, an increasement in lipid contents associated with decreased hormone-sensitive lipase (HSL) protein expression in testes in HFD-fed mice was observed, which could be improved by metformin treatment. Then, the model of TM4 mouse Sertoli cells stimulated with palmitic acid (PA) was used to investigate the potential effect of lipid retention on testicular apoptosis and sperm quality reduction. In consistent, PA exposure elevated lipid contents as well as apoptosis in TM4 cells, which could also be improved by metformin treatment. Of note, the protein expression of HSL was reduced stimulated by PA in TM4 cells, also rescued by metformin. Then, anti-apoptosis effect of metformin would be lost with the deficiency of HSL . In summary, our study propose that obesity contributes to oligoasthenospermia by increasing sperm apoptosis induced by impaired lipid hydrolysis due to HSL down-regulation, which could be prevented with metformin treatment via regulating the expression of HSL in testis in mice.
研究领域:
生殖生物学
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内分泌学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2018
·Vol. 8
·期 1
·1-11
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IF 4.122
Jiang Zhihui,Zhou Bo,Li Xinping,Kirby Gordon M.,Zhang Xiaoying
Male infertility is a major health issue with an estimated prevalence of 4.2% of male infertility worldwide. Our early work demonstrated that Cistanche extracts protect against sperm damage in mice and that echinacoside (ECH) is one of the major active components. Here we report an essential role for ECH, a natural product that reverses or protects against oligoasthenospermia in rats. ECH was assayed by HPLC, the quantity and quality of sperm was evaluated and hormone levels were determined by radioimmunosorbent assay. ECH reduced levels of androgen receptor (AR) and key steroidogenic-related genes as determined by Western blot and qPCR analysis. The interaction between ECH and AR were evaluated by indirect ELISA and molecular docking. The results show that ECH combined with hypothalamic AR in the pocket of Met-894 and Val-713 to inhibit transfer of AR from the cytoplasm to nuclei in the hypothalamus. While negative feedback of sex hormone regulation was inhibited, positive feedback was stimulated to increase the secretion of luteinizing hormone and testosterone subsequently enhancing the quantity of sperm. Taken together, these data demonstrate that ECH blocks AR activity in the hypothalamus to increase the quantity of sperm and protect against oligoasthenospermia in rats.
研究领域:
药理学
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生殖生物学
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分子生物学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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