PC6 levels in uterine lavage are closely associated with uterine receptivity and significantly lower in a subgroup of women with unexplained infertility

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Sophea Heng1, Natalie J. Hannan1, Luk J.F. Rombauts2, Lois A. Salamonsen1 and Guiying Nie1,*

1Prince Henry's Institute of Medical Research, PO Box 5152, 246 Clayton Rd, Clayton, VIC 3168, Australia

2Department of Obstetrics and Gynecology, Monash University, Clayton, VIC 3168, Australia *Correspondence address. Tel: +61-3-9594-4380; Fax: +61-3-9594-6125; E-mail: guiying.nie{at}princehenrys.orgReceived November 15, 2010. Revision received December 19, 2010. Accepted December 29, 2010. BACKGROUND Embryo implantation requires a healthy embryo and a receptive uterus. Uterine incompetence contributes significantly to implantation failure and infertility. To date, there are no reliable biochemical methods that can determine whether the uterus is receptive. Proprotein convertase 5/6 (PC6) is tightly regulated in the uterus and critical for receptivity and implantation; its secretory nature predicts PC6 to be secreted into the uterine cavity. The present study examines whether PC6 is detectable in uterine lavage and whether there is any correlation between secreted PC6 levels and uterine receptivity.

METHODS Western blotting determined the presence of PC6 protein in uterine lavage. A sensitive and high-throughput activity assay was established and validated. This assay was applied to 103 lavages collected from different phases of the menstrual cycle from women with proven fertility or unexplained infertility.

RESULTS Uterine lavage contained PC6 protein with levels paralleling enzymatic activity. PC6 levels were significantly higher in the receptive than in the non-receptive phase in fertile women, and the putative receptive phase levels in a subgroup of women with unexplained infertility were significantly lower than in the fertile counterparts.

CONCLUSIONS PC6 levels in uterine lavage are significantly elevated in the luteal phase of fertile women and markedly reduced in a subgroup of women with unexplained infertility. Uterine fluid is a valuable source of material to evaluate uterine function. Detection of PC6 in uterine fluid may lead to the development of a rapid and relatively non-surgical assessment of uterine receptivity.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 840-846. doi: 10.1093/humrep/der002 First published online: January 27, 2011

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