Dissecting the miR-451a-Mif Pathway in Endometriosis Pathophysiology Using a Syngeneic Mouse Model: Temporal Expression of Lesion Mif Receptors, Cd74 and Cxcr4

Abstract

Endometriosis is an enigmatic disease characterized by pain and infertility in which endometrial tissue grows in ectopic locations, predominantly the pelvic cavity. The pathogenesis and pathophysiology of endometriosis is complex and postulated to involve alterations in inflammatory, cell proliferation and post-transcriptional regulatory pathways among others. Our understanding on the pathogenesis and pathophysiology of endometriosis is further complicated by the fact that endometriosis can only be diagnosed by laparoscopy only after the disease has manifested. This makes it difficult to understand the true pathogenesis as a cause-and-effect relationship is difficult to ascertain. To aid in our understanding on endometriosis pathogenesis and pathophysiology, numerous rodent models have been developed. In this case, we discuss further assessment of a miR-451a—macrophage migration inhibitory factor (Mif) pathway which contributes to lesion survival. Specifically, we evaluate the temporal expression of lesion Mif receptors, Cd74 and Cxcr4 using host mice which express wild-type or miR-451a deficient lesions. Similar to that observed in humans and a non-human primate model of endometriosis, Cd74 expression is elevated in lesion tissue in a temporal fashion while that of Cxcr4 shows minimal increase during initial lesion establishment but is reduced later during the lifespan. Absence of miR-451a during initial lesion establishment is associated with an augmentation of Cd74, but no Cxcr4 expression. The data obtained in this study provide further support for a role of Mif receptors, Cd74 and Cxcr4 in the pathophysiology of endometriosis.

New Insights into Risk Factors for Postoperative Infections in Colorectal Cancer

“…Laparoscopic surgery, a signi cant advancement in modern science, has emerged as a new option for curative resection of colorectal cancer [67, 99,100]. It allows for precise observation of the surrounding tissue of the lesion, thus minimizing damage [101].…”

The Pathological Role of miRNAs in Endometriosis

“…miRNAs have highly stable structures and play a significant role in regulating various pathological processes during the formation of EMS, they are involved in controlling the adhesion, invasion, apoptosis, angiogenesis, and proliferation of endometriotic cells [185,189,190]. Within the cells, miRNAs directly participate in the post-transcriptional regulation of target genes, while outside the cells, they can bind to proteins or extracellular vesicles, thus avoiding degradation by ribonucleases [165,191].…”

Impact of Chronic Exposure to Endometriosis on Perinatal Outcomes: Establishment of a Mouse Model

“…To date, various rodent models of endometriosis have been established to elucidate its pathophysiology [ 5 , 6 , 7 , 8 ] and to test the efficacy of the treatment [ 9 , 10 , 11 ]. On the other hand, only a few rodent models have been reported to evaluate endometriosis-related adverse perinatal outcomes [ 12 , 13 , 14 , 15 , 16 ].…”