Dynamics of HOXA10 expression in ectopic endometrium of a mouse model of endometriosis

Abstract

Introduction: Homeobox gene A10 (HOXA10) is a transcription factor that plays a key role in maintaining endometrial homeostasis. In women with endometriosis, HOXA10 expression is downregulated, which is thought to cause progesterone resistance. However, it is unknown whether this downregulation is a cause or consequence of endometriosis. Materials and Methods: In this study, we used a mouse model of endometriosis and demonstrated that compared to the normal endometrium, the expression of HOXA10 is progressively downregulated during lesion development (from day 10 to day 65). Results: We observed that the expression of HOXA10 is lower in both well-differentiated and mixed types of endometriosis. During lesion development, the levels of HOXA10 were initially downregulated in epithelial cells more than in stromal cells. However, as the lesion development progressed further, the stromal expression was drastically reduced. While the nucleocytoplasmic ratio of HOXA10 was identical between control and endometriosis lesions at the initial stages, at later time points, HOXA10 remained largely nuclear, with little expression in the stroma. Conclusion: We conclude that the downregulation of HOXA10 is a consequence of endometriosis and may contribute toward its pathogenesis.