Enriched Environment Decelerates the Development of Endometriosis in Mouse

We tested the hypothesis that enriched environment (EE), consisting of enlarged space, and increased physical activity and social interactions, hinders the development of endometriosis through attenuated adrenergic signaling, enhanced autophagy, and reduced leptin levels. Two mouse experiments were performed. In Experiment 1, 40 female Balb/C mice were randomly divided into four equal-sized groups, the SE (standard environment), EE, p-EE (EE instituted after endometriosis induction), and the d-EE (SE housing but received uterine fragments from EE donors) groups. Housing intervention was initiated 3 weeks before the induction of endometriosis and continued for 3 weeks after induction. In Experiment 2, 20 female mice were randomly divided into SE and EE groups, and the plasma leptin levels were measured. We measured lesion weight and hotplate latency and performed Masson trichrome staining as well as immunohistochemistry analysis of β2 adrenergic receptor (ADRB2), dopamine receptor D2 (DRD2), vascular endothelial growth factor (VEGF), and microtubule-associated protein light chain 3 (LC3). We found that EE reduced the lesion weight by 40.8% as compared with SE mice, but the reduction in p-EE and d-EE mice did not reach statistical significance. EE significantly reduced staining levels of ADRB2 and VEGF as well as the extent of lesional fibrosis but increased staining levels of LC3 and DRD2 in lesions as compared with the SE group. EE mice had reduced plasma leptin levels as compared with SE mice. Thus, EE decelerates the development of endometriosis and fibrogenesis and improved generalized hyperalgesia, possibly through increased DRD2 expression but decreased expression of ADRB2 and VEGF as well as enhanced autophagy and reduced leptin level. Similar content being viewed by others

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Eur J Neurosci. 2004;20:1341–7. Acknowledgments We would like to thank two anonymous reviewers for their constructive comments and suggestions on an earlier version of this manuscript. Funding This research was supported in part by grants 81530040 (SWG), 81771553 (SWG), and 81671436 (XSL) from the National Science Foundation of China and an Excellence in Centers of Clinical Medicine grant (2017ZZ01016) from the Science and Technology Commission of Shanghai Municipality. Author information Authors and Affiliations Corresponding authors Ethics declarations Conflict of Interest The authors declare that they have no conflict(s) of interest. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material ESM 1 (download DOCX ) (DOCX 5373 kb) Rights and permissions About this article Cite this article Yin, B., Jiang, H., Liu, X. et al. Enriched Environment Decelerates the Development of Endometriosis in Mouse. Reprod. Sci. 27, 1423–1435 (2020). https://doi.org/10.1007/s43032-019-00117-1 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-019-00117-1