{"paper_id":"8fa66831-634b-4beb-bc0a-fa6aca02c426","body_text":"Abstract\nExtensive preclinical and clinical studies have shown that exposure to green light-emitting diodes (gLED) exerts analgesic effect. We hypothesized that exposure to gLED alleviates endometriosis-associated pain. To test this, we induced deep endometriosis in 16 Balb/C female mice. Four weeks post-induction, the mice were randomized into gLED and white LED (wLED) groups (n = 8 each), exposed daily to gLED (520–525 nm in wavelength) and wLED (500–700 nm), respectively, for 8 h over 2 weeks, and were then sacrificed. Endometriotic lesions were weighed and analyzed via immunohistochemistry for E-cadherin, α-Sma, phosphorylated Creb (p-Creb), adrenergic receptor β2 (Adrb2), α7 nicotinic acetylcholine receptor (α7nAChR), κ- and µ-opioid receptors (Kor and Mor), and cannabinoid receptor 1 and 2 (Cb1 and Cb2), alongside Masson trichrome staining. Pain and depression-like behavior was assessed via hotplate tests, tail suspension tests and sucrose preference tests, and serum noradrenaline levels were quantified. Exposed to gLED significantly reduced lesion weight, shortened tail suspension immobility time and increased hotplate latency compared to wLED. Lesions from gLED mice exhibited significantly reduced α-Sma staining, marginally reduced fibrosis, and elevated systemic noradrenaline. IHC analysis revealed significantly lower staining of p-Creb, Adrb2, Cb1 and Cb2 but increased α7nAChR and Mor staining in gLED lesions. These results demonstrate that exposure to gLED significantly alleviates endometriosis-induced pain while decelerates lesional progression in mice with induced deep endometriosis, possibly through the suppression of the Creb-Adrb2-Cb2 signaling pathway as well as increased systemic noradrenaline levels. 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We thank the two anonymous reviewers for their constructive and expert comments and suggestions on an earlier version of this manuscript.\nFunding\nThis research was funded by grant 82071623 (SWG) from the National Natural Science Foundation of China.\nAuthor information\nAuthors and Affiliations\nContributions\nJ.D.: Execution and implementation, data acquisition, initial data analysis, manuscript drafting, review and approval.\nX.L.: Study design, project supervision, manuscript writing, review and approval.\nY.W.: Randomization test analysis, manuscript review and revision, and approval.\nS.-W.G.: Study conception and design, funding, data analysis, manuscript drafting, revision and final approval.\nCorresponding author\nEthics declarations\nEthics Approval and Consent to Participate\nThe experiment was performed under the US National Research Council’s Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Experimental Animals Review Committee of Shanghai OB/GYN Hospital, Fudan University.\nConflict of interest\nJ.D., Y.W. and X.L. have no conflict of interest. S.W.G. is a member of the Scientific Advisory Board of Heranova BioSciences, FimmCyte A.G., E3A Healthcare, Foraviset, and Maipl Therapeutics and has provided consultancy advice to these companies, and received a travel support from Ziwig, but these activities had no bearing on this work.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nSupplementary Information\nBelow is the link to the electronic supplementary material.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nDong, J., Liu, X. & Guo, SW. Exposure to Green Light-emitting Diodes Alleviates Endometriosis-associated Pain in Mice with Induced Deep Endometriosis. Reprod. Sci. 33, 729–741 (2026). https://doi.org/10.1007/s43032-026-02084-w\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s43032-026-02084-w","source_license":"public-domain-us","license_restricted":false}