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体外补充瑞格列奈对改善正常精子和弱精子症患者精子运动参数、活力和 DNA 完整性的影响。

Effects of in vitro repaglinide supplementation on improving sperm motility parameters, viability, and DNA integrity in normozoospermic and asthenozoospermic men.

机构信息

Infertility Treatment Center of ACECR, Kermanshah, Iran.

Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.

出版信息

JBRA Assist Reprod. 2023 Sep 12;27(3):482-489. doi: 10.5935/1518-0557.20230038.

DOI:10.5935/1518-0557.20230038
PMID:37698460
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10712804/
Abstract

OBJECTIVE

Human sperm motility and hyperactivation (HA) are induced by different factors such as intracellular calcium concentration. Repaglinide is an antidiabetic drug that, via the blocking of ATP-sensitive potassium channels (K-ATP channels), depolarization of the β-cell membrane, and opening of the voltage-gated calcium channels leads to an increase in intracellular calcium. The present study aimed to examine the effects of repaglinide on in vitro sperm motility parameters, viability, and DNA integrity in normozoospermic and asthenozoospermic men.

METHODS

Semen samples were collected from two groups of normozoospermic donors and asthenozoospermic patients. The samples were washed free of seminal plasma and then treated with medium alone (control) or with 100 nM and 1µM concentrations of repaglinide. After 1 h of incubation, percent sperm motility and hyperactivation were assessed; after 2 h of incubation, sperm viability and DNA fragmentation rate were evaluated by the Eosin-Y and acridine orange staining, respectively.

RESULTS

In both groups, repaglinide at a concentration of 100 nM and 1µM significantly improved percent sperm motility, hyperactivation, and vital sperms with normal DNA; in specimens from normozoospermic men, the 1µM concentration had a noticeable effect on progressive motility; in samples from asthenozoospermic men, the highest hyperactivation rate was seen at a concentration of 100 nM as compared with the 1µM concentration and controls (p<0.05).

CONCLUSIONS

Our results suggest that repaglinide can improve sperm motility, hyperactivity, viability, and DNA integrity in both normozoospermic and asthenozoospermic men.

摘要

目的

人类精子的运动能力和超激活(HA)是由不同的因素诱导的,如细胞内钙离子浓度。瑞格列奈是一种抗糖尿病药物,通过阻断 ATP 敏感性钾通道(K-ATP 通道)、β细胞膜去极化和电压门控钙通道的开放,导致细胞内钙离子增加。本研究旨在研究瑞格列奈对正常精子和弱精子症患者体外精子运动参数、活力和 DNA 完整性的影响。

方法

从两组正常精子供体和弱精子症患者中收集精液样本。将样本洗脱去精液,然后用单独的培养基(对照)或 100 nM 和 1µM 浓度的瑞格列奈处理。孵育 1 小时后,评估精子运动百分比和超激活率;孵育 2 小时后,通过伊红 Y 和吖啶橙染色分别评估精子活力和 DNA 碎片率。

结果

在两组中,100 nM 和 1µM 浓度的瑞格列奈均显著提高了精子运动百分比、超激活率和具有正常 DNA 的活精子;在正常精子组的标本中,1µM 浓度对前向运动有明显影响;在弱精子症组的标本中,与 1µM 浓度和对照组相比,100 nM 浓度时出现了最高的超激活率(p<0.05)。

结论

我们的结果表明,瑞格列奈可以改善正常精子和弱精子症患者的精子运动能力、超活性、活力和 DNA 完整性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b92b/10712804/0b6f08a3f2c6/jbra-27-03-0482-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b92b/10712804/961ea69e82a9/jbra-27-03-0482-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b92b/10712804/00f4e263be66/jbra-27-03-0482-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b92b/10712804/0b6f08a3f2c6/jbra-27-03-0482-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b92b/10712804/961ea69e82a9/jbra-27-03-0482-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b92b/10712804/00f4e263be66/jbra-27-03-0482-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b92b/10712804/0b6f08a3f2c6/jbra-27-03-0482-g03.jpg

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本文引用的文献

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The Role of Sperm Proteins IZUMO1 and TMEM95 in Mammalian Fertilization: A Systematic Review.精子蛋白 IZUMO1 和 TMEM95 在哺乳动物受精中的作用:系统评价。
Int J Mol Sci. 2022 Apr 1;23(7):3929. doi: 10.3390/ijms23073929.
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Hum Reprod. 2022 Mar 1;37(3):466-475. doi: 10.1093/humrep/deac007.
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Current Insights and Latest Updates in Sperm Motility and Associated Applications in Assisted Reproduction.
精子活力的最新研究进展及其在辅助生殖中的相关应用
Reprod Sci. 2022 Jan;29(1):7-25. doi: 10.1007/s43032-020-00408-y. Epub 2020 Dec 7.
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Novel pharmacological actions of trequinsin hydrochloride improve human sperm cell motility and function.盐酸曲奎辛的新药理作用可改善人精子的运动和功能。
Br J Pharmacol. 2019 Dec;176(23):4521-4536. doi: 10.1111/bph.14814. Epub 2019 Dec 11.
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The beneficial effect of repaglinide on in vitro maturation and development ability of immature mouse oocytes.瑞格列奈对未成熟小鼠卵母细胞体外成熟及发育能力的有益作用。
In Vitro Cell Dev Biol Anim. 2017 Aug;53(7):626-631. doi: 10.1007/s11626-017-0152-3. Epub 2017 Apr 21.
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Drug discovery for male subfertility using high-throughput screening: a new approach to an unsolved problem.利用高通量筛选发现治疗男性生育力低下的药物:解决未解决问题的新方法。
Hum Reprod. 2017 May 1;32(5):974-984. doi: 10.1093/humrep/dex055.
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Antioxidant properties of repaglinide and its protections against cyclosporine A-induced renal tubular injury.瑞格列奈的抗氧化特性及其对环孢素A诱导的肾小管损伤的保护作用。
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Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF.精子膜电位去极化是男性生育力低下的一个常见特征,并且与体外受精时的低受精率相关。
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