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

Yohan Choi, Ji Yeon Park, Kalin Wilson, Katherine L. Rosewell, Mats Brännström, James W. Akin, Thomas E. Curry, Misung Jo

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish
Pages (from-to)1256-1266
Number of pages11
JournalBiology of Reproduction
Volume96
Issue number6
DOIs
StatePublished - Jun 2017

Bibliographical note

Funding Information:
1Department of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky, USA; 2Department of Obstetrics and Gynecology, University of Gothenburg, Gothenburg, and Stockholm IVF, Stockholm, Sweden and 3Bluegrass Fertility Center, Lexington, Kentucky, USA ∗Correspondence: Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0298, USA. Tel: 859-323-5800; Fax: 859-257-4742. E-mail: mjo2@uky.edu †Grant Support: This research was supported by the Lalor Foundation Postdoctoral Fellowship (YC and PH), R01HD061617 (MJ), PO1HD71875 (MJ, TEC, and MB) and the BTPSRF of the University of Kentucky Markey Cancer Center (P30CA177558).

Publisher Copyright:
© The Authors 2017.

Keywords

  • CXCL12
  • CXCR4
  • Granulosa cells
  • Human
  • Progesterone receptor

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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