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The expression of CXCR4 is induced by the luteinizing hormone surge and mediated by progesterone receptors in human preovulatory granulosa cells

Journal article
Authors Y. Choi
J. Y. Park
K. Wilson
K. L. Rosewell
Mats Brännström
J. W. Akin
T. E. Curry
M. Jo
Published in Biology of Reproduction
Volume 96
Issue 6
Pages 1256-1266
ISSN 0006-3363
Publication year 2017
Published at Institute of Clinical Sciences, Section for the Health of Women and Children, Department of Obstetrics and Gynecology
Pages 1256-1266
Language English
Links doi.org/10.1093/biolre/iox054
Keywords CXCL12, CXCR4, granulosa cells, progesterone receptor, human, human chorionic-gonadotropin, migration inhibitory factor, chemokine, receptors, human ovary, factor-i, follicles, ovulation, gene, recruitment, ligand, Reproductive Biology
Subject categories Obstetrics, Gynecology and Reproductive Medicine

Abstract

The chemokine CXC motif ligand 12 (CXCL12) and its cognate receptor, CXCR4, have been implicated in the ovulatory process in various animal models. However, little is known about the expression and regulation of CXCL12 and CXCR4 and their functions during the ovulatory period in the human ovary. In this study, we characterized the expression patterns of CXCL12 and CXCR4 in preovulatory follicles collected before the luteinizing hormone (LH) surge and at defined hours after hCG administration in women with the regular menstrual cycle. The levels of mRNA and protein for CXCR4 were increased in granulosa cells of late ovulatory follicles, whereas CXCL12 expression was constant in follicles throughout the ovulatory period. Both CXCR4 and CXCL12 were localized to a subset of leukocytes around and inside the vasculature of human preovulatory follicles. Using a human granulosa cell culture model, the regulatory mechanisms and functions of CXCL12 and CXCR4 expression were investigated. Human chorionic gonadotropin (hCG) stimulated CXCR4 expression, whereas CXCL12 expression was not affected, mimicking in vivo expression patterns. Both RU486 (progesterone receptor antagonist) and CoCl2 (HIFs activator) blocked the hCG-induced increase in CXCR4 expression, whereas AG1478 (EGFR inhibitor) had no effect. The treatment with CXCL12 had no effect on granulosa cell viability but decreased hCG-stimulated CXCR4 expression. In conclusion, these results suggest that the CXCL12/CXCR4 system plays a role(s) in the LH surgeinduced follicular changes and infiltration of leukocytes in dominant follicles during the ovulatory period in humans.

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