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Mouse model for endometriosis is characterized by proliferation and inflammation but not epithelial-to-mesenchymal transition and fibrosis

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Abstract

Endometriosis is a common disorder of unknown etiology, and non-surgical therapies are still a challenge. To understand the pathogenesis and preclinical testing of drugs for endometriosis, animal models are highly desirous. Herein, we carried out longitudinal characterization of a mouse model for endometriosis where uterine tissue was transplanted onto the intestinal mesentery. During the course of lesion development from day 15 to 60 post-induction, the ectopic endometrium became pale, fluid-filled and the animals developed peritoneal adhesions. Most lesions resembled a well-differentiated type of endometriosis and ~ 13% of animals had mixed type of lesions. There was extensive stromal compaction in the ectopic tissue. During the progression of endometriosis, there was increased proliferation of epithelial and stromal cells as evident by PCNA staining. Cyp19a1 (aromatase) mRNA was detected in the ectopic lesions on day 15 and 30 post-induction of endometriosis, by day 60 the expression was reduced. As compared to the control endometrium, the mRNA levels of Esr1 progressively reduced while the levels of inflammation associated genes (Esr2, Ifng, Tnf and Il1b) increased in the ectopic lesions. Infiltration of macrophages and polymorphonuclear leucocytes was also observed in the ectopic lesions indicative of inflammation. As compared to control, there was no change in levels of Cytokeratin and E-cadherin in the epithelial cells of ectopic endometrium. We did not observe excessive collagen deposition or α-SMA positive myofibroblasts in the stroma of the ectopic endometrium. Thus, epithelial-to-mesenchymal transition and fibrosis are not detected in the mouse model of endometriosis. Our results show that the mouse model of endometriosis mimics some but not all the features of human endometriosis.

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Acknowledgements

We express our gratitude to Dr Lalita Shankar Savardekar for sparing the Artisan™ Masson’s Trichrome Stain Kit. We thank the staff of the Animal House (NIRRH) for their help during surgeries and animal maintenance. The help of Dr Atahar Husein in editing the manuscript is gratefully acknowledged. The manuscript bears the NIRRH ID: RA/791/08–2019. DM’s lab is funded by grants from ICMR, India. The study was funded by grants from the Department of Biotechnology (DBT), India (BT/OR6587/MED/30/886/2012) to DM. AM is the recipient of the Junior and Senior Research fellowship from the University Grants Commission (UGC), India. MG was the recipient of the ICMR postdoctoral fellowship (sixth batch).

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Authors and Affiliations

  1. Molecular and Cellular Biology Laboratory, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), Mumbai, 400 012, India

    Anuradha Mishra, Mosami Galvankar, Shantashri Vaidya & Deepak Modi

  2. Primate Biology Laboratory, ICMR-National Institute for Research in Reproductive Health, Indian Council of Medical Research (ICMR), Mumbai, 400 012, India

    Uddhav Chaudhari

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  1. Anuradha Mishra
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  2. Mosami Galvankar
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  5. Deepak Modi
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Correspondence to Deepak Modi.

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Communicated by Ullas Kolthur-Seetharam.

Corresponding editor: Ullas Kolthur-Seetharam

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Mishra, A., Galvankar, M., Vaidya, S. et al. Mouse model for endometriosis is characterized by proliferation and inflammation but not epithelial-to-mesenchymal transition and fibrosis. J Biosci 45, 105 (2020). https://doi.org/10.1007/s12038-020-00073-y

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