Gene Expression in Endometriosis

  • Niraj Joshi
  • Ren-Wei Su
  • Asgerally FazleabasEmail author


Endometriosis is a common gynecological disorder defined by the presence of endometrial tissue outside the uterus which affects 10–15% of women and is associated with pelvic pain and infertility. It is an estrogen-dependent, inflammatory disease associated with elevated tissue, peripheral and peritoneal cytokines. The presence of the disease results in aberrant gene expression in the eutopic endometrium, development of progesterone resistance, and impaired decidualization. The molecular mechanisms driving these phenotypic changes in both the eutopic and ectopic endometrium are not clear. Therefore, to study the mechanisms of disease onset and early development, animal models in which the onset of disease can be exactly controlled are necessary. The use of nonhuman primates is advantageous for the study of endometriosis because they are phylogenetically similar to humans. Among all the available nonhuman primate models, the baboon (Papio anubis) is preferred because of its size, similar reproductive anatomy and physiology, and the ability to evaluate disease pathogenesis from the onset of disease induction. This chapter summarizes our findings on how the presence of ectopic lesions influences the eutopic endometrial gene signature leading to altered endometrial function, progesterone resistance, and impaired decidualization. We suggest that the presence of endometriosis leads to rapid and significant changes in the expression of several microRNAs (miRNAs) which in turn may impact the altered gene signature contributing to the pathology of the disease including progesterone resistance. Notch signaling plays a vital role in cell survival, cellular communication, and differentiation throughout development in a variety of species. We document that decreased NOTCH1 signaling in eutopic endometrium compromises decidualization. Additionally, we demonstrate that altered signaling pathways (AKT, MAPK, ERK, and HIF1A-STAT3) along with epigenetic changes further contribute to progesterone resistance and decidualization defects. Thus, inflammation and altered microRNA expression, in both the eutopic and ectopic endometrium, impact the progesterone-regulated gene networks leading to compromised endometrial function as a consequence of endometriosis.


Endometriosis Progesterone resistance Decidualization microRNA Gene expression 



Portions of this research were supported by grants from the Eunice Kennedy Shriver NICHD R01-HD083273 and R01-HD042280 to Prof. Asgerally Fazleabas and SRI-Bayer Discovery grant to Dr. Niraj Joshi. The authors would like to thank the members of Fazleabas Laboratory at Michigan State University for their support in carrying out these experiments.


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Obstetrics, Gynecology and Reproductive BiologyCollege of Human Medicine, Michigan State UniversityGrand RapidsUSA
  2. 2.College of Veterinary Medicine, South China Agricultural UniversityGuangzhou, GuangdongChina

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