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.
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.
The PC6 inhibitor C1239-PEG-Poly R inhibited in a dose-dependent manner both decidualization and spheroid attachment. Vaginal delivery of 200 ��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.
This study presents proof of concept that PC6 inhibition has the potential to block embryo implantation, providing nonhormonal contraception for women.
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Published online: November 14, 2011
Accepted: October 5, 2011
Received in revised form: October 4, 2011
Received: September 13, 2011
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.