Low calcitonin receptor like receptor expression in endometrial vessels from women with unexplained infertility

Abstract

Adrenomedullin (AM) and its receptor subunit, calcitonin receptor-like receptor (CLR) are known to be important for endothelial function. The genotypes and phenotypes of AM and CLR in the endometrium were studied in relation to unexplained infertility. Endometrial biopsies from 12 fertile and 11 infertile women and blood samples from 156 fertile and 106 infertile women were collected. Protein and mRNA expression of AM and CLR was determined using immunohistochemistry and real time PCR. Allele and genotype frequencies in the AM (rs4399321 and rs7944706) and CLR genes (rs696574, rs1528233 and rs3771073) were performed using Taqman genotyping assays. Unexplained infertility was characterised by lower number of vessels stained with CLR in endometrium compared to fertile controls. There was no difference in AM expression. This could not be explained by SNP analysis in the AM or CLR genes. Imbalance in the AM/CLR system might alter endothelial function in women with unexplained infertility.

Keywords:

• Adrenomedullin
• unexplained infertility
• calcitonin receptor-like receptor
• polymorphism

Acknowledgements

The authors thank Dr. Leonid Nikitenko for provision of the CLR antibody. They would like to thank Dr. David Poyner, University of Aston, Birmingham, UK for his helpful comments. Support from the Swedish Research Council (2005-7293), Swedish Medical Society, Åke Wibergs Foundation, Magn Bergvalls Foundation, Family planning foundation, Uppsala University and Karolinska Institutet is greatly acknowledged.