Inhibition of proprotein convertase 5/6 activity: potential for nonhormonal women-centered contraception

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• 作者：Mohamad Aljofan^a ; ^{Mo.aljofan@monash.edu} ; Harmeet Singh^a ; Huiting Ho^a ; ^b ; Shuwu Xie^c ; Yan Zhu^c ; Zhaogui Sun^c ; Xiangjie Guo^c ; Jian Wang^b ; Guiying Nie^a
• 关键词：Proprotein convertase 5/6 ; Female contraception ; Embryo implantation ; Decidualization ; Vaginal delivery
• 刊名：Contraception
• 出版年：2012
• 期刊代码：71_00107824
• 类别：med
• 出版时间：June, 2012
• 卷：85
• 期：6
• 页码：602-610
• 文件大小：737 K

摘要

Background

Proprotein convertase 5/6 (PC6) is critical for endometrial epithelial receptivity and stromal cell decidualization for embryo implantation in women. We hypothesized that inhibiting PC6 could block implantation for contraception. The aim of this study was to prove this concept using human cell models and rabbits.

Study Design

A potential PC6 inhibitor, C1239-PEG-Poly R, was biochemically confirmed to be a potent PC6 inhibitor. The potential contraceptive action of the inhibitor was then tested in decidualization of primary human endometrial stromal cells in a human trophoblast spheroid attachment model and in vivo in rabbits.

Results

The PC6 inhibitor C1239-PEG-Poly R inhibited in a dose-dependent manner both decidualization and spheroid attachment. Vaginal delivery of 200 渭L of the inhibitor at a final concentration of 5 mM to rabbits over a 3-day period starting 6 days after mating resulted in a 60%decrease in implantation and, hence, pregnancy.

Conclusions

This study presents proof of concept that PC6 inhibition has the potential to block embryo implantation, providing nonhormonal contraception for women.