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

Mohamad Aljofan, Harmeet Singh, Huiting Ho, Shuwu Xie, Yan Zhu, Zhaogui Sun, Xiangjie Guo, Jian Wang, Guiying Nie

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

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 muL 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.
Original languageEnglish
Pages (from-to)602 - 610
Number of pages9
JournalContraception
Volume85
Issue number6
DOIs
Publication statusPublished - 2012

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