The CXL12/CXCR4/CXCR7 axis in female reproductive tract disease: Review

Initial studies on the chemokine stromal derived factor 1 (now referred to as CXCL12) were proposed to be enhanced in several diseases including those which affect the female reproductive tract. These include endometriosis, Asherman's syndrome, endometrial cancers, and ovarian cancers. Additionally, recent studies from our laboratory suggest that CXCL12 signaling is involved in leiomyomas (fibroids). These diseases present an inflammatory/hypoxic environment which further promotes pathology. At first, studies focused on signaling by CXCL12 via its well-known receptor, CXCR4. However, the discovery of CXCR7 as another receptor for CXCL12 with rather high binding affinity and recent reports about its involvement in endometrial disease and cancer progression has questioned the potential of "selective blockade"' of CXCR4 to treat these ailments. This review will focus on the signaling and effects of the potent chemokine CXCL12, and its long-known G protein-coupled receptor CXCR4, as well as the alternate receptor CXCR7 on the female reproductive tract and related diseases such as endometriosis, Asherman's syndrome, leiomyomas, endometrial cancer, and ovarian cancer. Although several other mechanisms are inherent to these diseases such as gene mutations, differential expression of miRNAs and epigenetics, for this review, we will focus on the CXCL12/CXCR4/CXCR7 axis as a novel target.