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Spatial and temporal changes in the expression of steroid hormone receptors in mouse model of endometriosis

Journal of Assisted Reproduction and Genetics volume 37, pages 1069–1081 (2020)Cite this article

Abstract

Purpose

Endometriosis is recognized as a steroid hormone-dependent disorder. However, controversies exist regarding the status of the steroid hormone receptor expression in endometriotic tissues. The purpose of this study was to determine the ontogeny of cellular changes in the expression of estrogen receptors (ERα, ERβ), G protein-coupled estrogen receptor 1 (GPER1), and progesterone receptors (PRs) in endometriosis using a mouse model.

Methods

We used the autologous uterine tissue transfer mouse model and studied the mRNA and protein expression of ERα, ERβ, GPER1, and PR in ectopic lesions at 2, 4, and 8 weeks of induction of endometriosis.

Result

As compared to endometrium of controls, in the ectopic endometrium, ERα is reduced while ERβ was elevated in stromal cells; however, Gper1 and PR levels are reduced in both stromal and epithelial cells in a time-specific manner. There is a high inter-animal variation in the levels of these receptors in ectopic endometrium as compared to controls; the levels also varied by almost 100-fold within the same lesion resulting in “micro-heterogeneity.” The expression of all these receptors also deferred between two lesions from the same animal.

Conclusion

In the endometriotic tissue, there is extensive inter-animal and intra-lesion heterogeneity in the expression of ERα, ERβ, GPER1, and PR. These changes are not due to the influence of the peritoneal environment but appear to be tissue intrinsic. We propose that the variable outcomes in hormonal therapy for endometriosis could be possibly due to heterogeneity in the expression of steroid hormone receptors in the ectopic endometrium.

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Acknowledgments

We express our gratitude to Dr. Stacy Colaco and Mr. Abhishek Tiwari for help during the preparation of the manuscript. We thank Dr. Uddhav Chaudhari and the staff of the Animal House (NIRRH) for their help during surgeries and animal maintenance.

Funding

The manuscript bears the NIRRH ID: RA/756/03–2019. DM lab is funded by grants from ICMR, Govt of India. The study was funded by grants from the Department of Biotechnology (DBT); (BT/OR6587/MED/30/886/2012) and Department of Science and Technology (SR/SO/HS-0277/2012) Govt of India to DM. AM is a recipient of the junior and senior research fellowship from the University Grants Commission (UGC), Govt of India. MG was the recipient of the ICMR postdoctoral fellowship (6thBatch). NS is a recipient of the senior research fellowship from ICMR.

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Author notes

  1. Anuradha Mishra and Mosami Galvankar contributed equally to this work.

Authors and Affiliations

  1. Molecular and Cellular Biology Laboratory, ICMR-National Institute for Research in Reproductive Health, J.M. Street, Parel, Mumbai, 400012, India

    Anuradha Mishra, Mosami Galvankar, Neha Singh & Deepak Modi

Authors
  1. Anuradha Mishra
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  2. Mosami Galvankar
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  3. Neha Singh
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  4. Deepak Modi
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Corresponding author

Correspondence to Deepak Modi.

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This study was approved by the Institutional Animal Ethics Committee (IAEC) of the National Institute for Research in Reproductive Health (NIRRH), project number (05/12).

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The authors declare that there is no conflict of interest.

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Mishra, A., Galvankar, M., Singh, N. et al. Spatial and temporal changes in the expression of steroid hormone receptors in mouse model of endometriosis. J Assist Reprod Genet 37, 1069–1081 (2020). https://doi.org/10.1007/s10815-020-01725-6

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