Molecular Human Reproduction, Vol. 9, No. 4, 189-198,
April 2003
© 2003 European Society of Human Reproduction and Embryology
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Hormonal and embryonic regulation of chemokine receptors CXCR1, CXCR4, CCR5 and CCR2B in the human endometrium and the human blastocyst
Submitted on July 30, 2002; resubmitted on September 5, 2002. accepted on December 13, 2002
1 Instituto Valenciano de Infertilidad Foundation (FIVIER) and 2 Department of Pediatrics, Obstetrics and Gynecology, Valencia University School of Medicine, Valencia and 3 Department of Obstetrics and Gynecology Hospital Dr. Peset, Valencia, Spain
4 To whom correspondence should be addressed at: Instituto Valenciano de Infertilidad, Plaza de la Policia Local 4 Valencia 46015, Spain. e-mail: csimon{at}interbook.net
Chemokines are implicated in the implantation process. The aim of this study was to investigate mRNA expression and protein levels of chemokine receptors CXCR1, CXCR4, CCR5 and CCR2B in human endometrium throughout the menstrual cycle, during HRT and in the human blastocyst. The regulation of chemokine receptors in the endometrial epithelium was also studied using an in-vitro model for the apposition phase of human implantation. We found up-regulation of endometrial CXCR1 mRNA (419-fold increase), CCR5 mRNA (612-fold increase) and CCR2B mRNA (657 fold-increase) during the luteal phase peaking in the pre-menstrual endometrium. CXCR4 mRNA levels presented a specific although modest (18-fold increase) up-regulation during the implantation window. These findings were corroborated at the protein level in natural and HRT cycles. Immunoreactive CCR5 and CCR2B receptors were detected in human blastocysts whereas CXCR4 and CXCR1 were not present. Chemokine receptors in cultured endometrial epithelial cells showed an up-regulation and polarization of CXCR1, CXCR4 and CCR5 receptors when a human blastocyst was present. The specific distribution and regulation of chemokine receptors in the endometrial epithelium and the human blastocyst suggest a possible implication of these receptors in the apposition and adhesion phases of human implantation.
Key words: blastocyst/chemokine receptors/endometrial epithelial cells/human endometrium/implantation
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