DNA Microarray Technology may Identify Differential Gene Expression in the Endometrial Tissue of Infertile Women with Endometriosis Compared to Fertile Controls: A Prospective Study

Background and Significance: Controversy exists regarding the pathogenesis of endometriosis. Abnormalities in the endometrium of women with endometriosis could predispose to attachment and growth of these cells on the peritoneum and ovaries. If the endometrial tissue is abnormal, alterations in gene expression should be detected using DNA microarray technology. Objective: To use DNA microarray technology to examine differential gene expression in the endometrial tissue of infertile women with endometriosis compared to that of fertile controls. Materials and Methods: In this prospective, IRB approved study, enrollment included 10 case women undergoing laparoscopic surgery for infertility, 5 with ASRM stage I to II disease and 5 with stage III to IV disease. The five controls were fertile women undergoing laparoscopic tubal sterilization with a visually normal pelvis. All had regular cycles and were operated on in the mid-follicular phase. A pipelle endometrial biopsy was performed immediately before laparoscopy or uterine manipulation. DNA microarray technology was applied to the mRNA extracted from each of the biopsy samples to determine changes in gene expression between cases and controls. Results: IGF binding protein 1 (IGF-BP1) was 30 fold down regulated and interleukin receptor 1 was 10 fold down regulated in the endometrium of all cases when compared to controls, regardless of the severity of the disease. Matrix metalloproteinases (MMPs) 1,3, 10 and 12 were found to be 10 to 30 fold down regulated in stage I to II endometriosis compared to controls, but were not different when stage III to IV cases were compared to the controls. Several other genes, whose significance in the pathogenesis of endometriosis is undescribed, were also found to be differentially expressed. Conclusions: A decrease in gene expression for both the MMPs and interleukin receptor-1 may contribute to the abnormal implantation and growth of endometriosis. The decreased gene expression of IGF-BP1 may provide an explanation for the increased infertility associated with the disease. If our findings are supported in other studies, it is possible that office endometrial biopsy could be used as a minimally invasive technique to both diagnose and stage endometriosis.