Evaluation of the novel vaginal contraceptive agent PPCM in preclinical studies using sperm hyaluronan binding and acrosome status assays.
Evaluation of the novel vaginal contraceptive agent PPCM in preclinical studies using sperm hyaluronan binding and acrosome status assays.
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DOI：
10.1111/andr.13110
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发表时间：
2022-03
期刊：
影响因子：
4.5
通讯作者：
Prins GS
中科院分区：
文献类型：
--
作者：
North BB;Weitzel MB;Waller DP;Birch WX;Feathergill KA;Birch LA;De Jonge CJ;Prins GS
聚亚苯基羧甲撑钠（PPCM）是一种很有前途的多用途技术，用于预防性传播感染（STI）和妊娠。在临床前研究中，PPCM已证明具有显著的（1）抗几种重要病毒和细菌病原体的抗菌活性和（2）与顶体过早丢失相关的避孕活性。利用重新利用的透明质酸结合试验（HBA）在临床前研究中进一步评估阴道抗菌化合物作为避孕药的作用。用浓度递增的PPCM或钙离子载体A23187（阳性对照）处理含有纯精液或洗涤精子的精液样本。通过两种方法测量精子灭活：（1）双重顶体染色（AS）和（2）透明质酸结合试验（HBA®）。比较未处理对照精子与用PPCM或A23187处理的精子之间的失活精子百分比。在两种试验中，PPCM对精子灭活具有显著（p < 0.05）和剂量依赖性影响，HBA检测到的灭活精子比例高于AS。PPCM不影响精子活力，在纯样本和清洗样本中表现出等同的反应。HBA和AS均证实，在实际使用条件下，在阴道中可能存在的PPCM浓度下，精子被快速灭活，时间范围与精子从精浆中体内迁移到宫颈粘液中相当。PPCM阴道凝胶可以提供避孕保护以及帮助预防性传播感染。HBA可能是一个敏感的和急需的精子活性的生物标志物，在未来的避孕发展。
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. To further evaluate a vaginal antimicrobial compound as a contraceptive agent in preclinical studies utilizing a repurposed hyaluronan binding assay (HBA). 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. 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. 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. 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.
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