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采用精子透明质酸结合和顶体状态检测方法评估新型阴道避孕剂 PPCM 在临床前研究中的效果。

Evaluation of the novel vaginal contraceptive agent PPCM in preclinical studies using sperm hyaluronan binding and acrosome status assays.

机构信息

Yaso Therapeutics Inc., Frisco, Texas, USA.

College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA.

出版信息

Andrology. 2022 Feb;10(2):367-376. doi: 10.1111/andr.13110. Epub 2021 Oct 4.

DOI:10.1111/andr.13110
PMID:34542939
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8760152/
Abstract

BACKGROUND

Polyphenylene carboxymethylene (PPCM) sodium salt is a promising multipurpose technology for prevention of both sexually transmitted infections (STIs) and pregnancy. In preclinical studies, PPCM has demonstrated significant (1) antimicrobial activity against several important viral and bacterial pathogens and (2) contraceptive activity associated with premature acrosome loss.

OBJECTIVE

To further evaluate a vaginal antimicrobial compound as a contraceptive agent in preclinical studies utilizing a repurposed hyaluronan binding assay (HBA).

MATERIALS AND METHODS

Semen samples containing either neat semen or washed spermatozoa were treated with increasing concentrations of PPCM or calcium ionophore A23187 (positive control). Sperm inactivation was measured by two methods: (1) double acrosome staining (AS), and (2) a hyaluronan binding assay (HBA ). Percentage of inactivated sperm was compared between untreated control sperm and those treated with PPCM or A23187.

RESULTS

PPCM had a significant (p < 0.05) and dose-dependent effect on sperm inactivation in both assays, with HBA detecting a higher proportion of inactivated sperm than AS. PPCM did not affect sperm motility and exhibited equivalent responses in the neat and washed samples.

DISCUSSION

Both HBA and AS confirmed that spermatozoa were rapidly inactivated at PPCM concentrations likely present in the vagina under actual use conditions and in a time-frame comparable to in vivo migration of spermatozoa out of seminal plasma into cervical mucus.

CONCLUSION

PPCM vaginal gel may provide contraceptive protection as well as help with STI prevention. HBA may be a sensitive and much needed biomarker for sperm activity in future contraceptive development.

摘要

背景

聚对苯二甲酸亚苯基羧甲基钠(PPCM)是一种有前途的多用途技术,可预防性传播感染(STIs)和妊娠。在临床前研究中,PPCM 已显示出对几种重要的病毒和细菌病原体的显著(1)抗菌活性,以及(2)与顶体过早丢失相关的避孕活性。

目的

利用重新利用的透明质酸结合测定法(HBA)进一步评估阴道抗菌化合物作为避孕剂在临床前研究中的应用。

材料和方法

含有新鲜精液或洗涤精子的精液样本用递增浓度的 PPCM 或钙离子载体 A23187(阳性对照)处理。通过两种方法测量精子失活:(1)双重顶体染色(AS),和(2)透明质酸结合测定法(HBA)。将未处理的对照精子与用 PPCM 或 A23187 处理的精子的失活精子百分比进行比较。

结果

PPCM 在两种测定中均对精子失活具有显著(p<0.05)和剂量依赖性作用,HBA 检测到的失活精子比例高于 AS。PPCM 不影响精子活力,在未处理和洗涤样本中表现出相同的反应。

讨论

HBA 和 AS 均证实,在实际使用条件下阴道中可能存在的 PPCM 浓度以及与精子从精液中迁移到宫颈粘液中的体内迁移时间相当的时间范围内,精子迅速失活。

结论

PPCM 阴道凝胶可能提供避孕保护,并有助于预防性传播感染。HBA 可能是未来避孕剂开发中精子活性的敏感且急需的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b4/9135057/6e38a0a2f0d5/ANDR-10--g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b4/9135057/026b52d77ff6/ANDR-10--g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b4/9135057/ece9a6dc8d77/ANDR-10--g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b4/9135057/7b2062c6e30f/ANDR-10--g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b4/9135057/6e38a0a2f0d5/ANDR-10--g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b4/9135057/026b52d77ff6/ANDR-10--g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b4/9135057/ece9a6dc8d77/ANDR-10--g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b4/9135057/7b2062c6e30f/ANDR-10--g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86b4/9135057/6e38a0a2f0d5/ANDR-10--g004.jpg

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