{"paper_id":"015e9b91-7f51-4b95-8f5c-7b8dbdf48d4d","body_text":"Abstract\nEndometriosis is illustrated by the presence of ectopic endometrial cells capable of evading apoptosis outside the uterus. Apoptotic and anti-apoptotic factors in the extra uterine microenvironment can be compromised by the impairment in oxidative status. Angiotensin Converting Enzyme (ACE) Inhibitors and Nitric Oxide (NO) modulators play pivotal role in inflammation, angiogenesis, apoptosis and in abrogating oxidative imbalance. Therefore, in the current study we investigate the role of ACE inhibitor and or NO modulators in mitigating the proliferation of ectopic endometrial lesions in rat model. Sixty adult female virgin wistar rats were utilized; out of which fifteen were used as donor rats and rest forty-two were randomly divided into seven groups after surgical implantation of endometrial explants into rats (group II–VII). Histomorphometric assessment of uteri and ectopic lesions was performed by Hematoxylin and eosin (H-E) staining, followed by immunohistochemical study for Proliferating cell nuclear antigen (PCNA), Bax and Bcl-2. Oxidative stress parameters were evaluated by biochemical estimations, succeeded by immunoblotting of Poly [ADP-ribose] polymerase 1 (PARP1). Additionally, immunoblotting of Vascular endothelial growth factor (VEGF), Bax, Bcl-2 and caspase-3 was also performed. Significant decrease in the diameter of lesions with diffused staining at the extracellular spaces of stromal cells for PCNA accompanied by significant decrease in the expression of VEGF (p < 0.00001) was observed in group III. Furthermore, increased expression of Bax:Bcl-2 ratio (p < 0.001) and cleaved caspase-3 (p ≤ 0.0001) in ectopic lesions of group III was also observed. Administration of ramipril alone results in triggering oxidative stress mediated cleavage of PARP1, augmenting apoptosis in the ectopic lesions.\nSimilar content being viewed by others\nData availability\nNo datasets were generated or analysed during the current study.\nAbbreviations\n- OVX:\n-\nOvariectomy\n- ACE:\n-\nAngiotensin converting enzyme\n- NO:\n-\nNitric oxide\n- SNP:\n-\nSodium nitroprusside\n- L-NAME:\n-\nNω-Nitro-L-arginine methyl ester hydrochloride\n- PCNA:\n-\nProliferating cell nuclear antigen\n- PARP1:\n-\nPoly (ADP-ribose) polymerase 1\n- ROS:\n-\nReactive oxygen species\n- SOD:\n-\nSuperoxide dismutase\n- CAT:\n-\nCatalase\n- MDA:\n-\nMalondialdehyde\n- PBS:\n-\nPhosphate buffer saline\n- TBA-TCA:\n-\n2-Thiobarbituric acid-trichloroacetic acid\n- DCFH-DA:\n-\n2′,7′-Dichlorodihydrofuorescein diacetate\n- VCl3 :\n-\nVanadium (III) chloride\n- NEDD:\n-\nN-(1-Naphthyl) ethylenediamine dihydrochloride\n- SULF:\n-\nSulfanilamide\n- BSA:\n-\nBovine serum albumin\n- RIPA:\n-\nRadioimmunoprecipitation assay buffer\n- NBT:\n-\nNitro blue tetrazolium\n- BCIP:\n-\n5-Bromo-4-chloro-3-indoyl-phosphate\n- AP:\n-\nAlkaline phosphatase\n- HRP:\n-\nHorseradish peroxidase\n- BCA:\n-\nBicinchoninic acid method\n- HE:\n-\nHematoxylin-Eosin\n- EDTA:\n-\nEthylenediamine tetraacetic acid\nReferences\nAgarwal A, Gupta S, Sharma RK (2005) Role of oxidative stress in female reproduction. 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We are also grateful to DST-FIST ((DLS[SR/FST/LSI-560/2013(C)]), Government of India and DBT-BUILDER (BT/INF/22/SP45088/2022).\nAuthor information\nAuthors and Affiliations\nContributions\nPM has conceptualized, investigated, designed & performed the experiments, analyzed the results and written the original draft. SSB has conceptualized, supervised, acquired fund and laboratory resources, and revised the original draft. Both the authors reviewed the manuscript before the final submission.\nCorresponding author\nEthics declarations\nConflict of interest\nThe authors declare no competing interests.\nEthics approval and consent to participate\nAll animal procedures were performed in accordance with the Committee for Control and Supervision of Experiments on Animals (CCSEA) guidelines for the Humane Care of Laboratory Animals. All procedures were approved by the Presidency University, Kolkata, India University Institutional Animals Care and Use Committee.\nConsent for publication\nNot applicable.\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.\n10735_2025_10397_MOESM2_ESM.tif (download TIF )\nFig. S2 Immunohistochemical localization pattern of PCNA, Bax and Bcl-2 in the eutopic uterine section under 100X oil immersion. Representative photomicrographs of uterine sections stained for PCNA in Group I (a), Group II (b), Group III (c), Group IV (d), Group V (e), Group VI (f) and Group VII (g); for Bax in Group I (h), Group II (i), Group III (j), Group IV (k), Group V (l), Group VI (m) and Group VII (n); for Bcl-2 in Group I (o), Group II (p), Group III (q), Group IV (r), Group V (s), Group VI (t) and Group VII (u). Black thick arrows represent the distinctive pattern of PCNA, Bax and Bcl-2 in the endometrium lining\n10735_2025_10397_MOESM3_ESM.tif (download TIF )\nFig. S3 Immunohistochemical localization pattern of PCNA, Bax and Bcl-2 in the ectopic lesion under 100X oil immersion. Pictorial representation of ectopic endometrial sections stained for PCNA in Group II (a), Group III (b), Group IV (c), Group V (d), Group VI (e) and group VII (f); for Bax in Group II (g), Group III (h), Group IV (i'), Group V (j), Group VI (k) and Group VII (l); for Bcl-2 in Group II (m), Group III (n), Group IV (o), Group V (p), Group VI (q) and group VII (r). Blue thick arrows represent variable staining pattern of Bax and Bcl-2 in the ectopic endometrial glands and stroma\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\nMazumdar, P., Biswas, S.S. Ramipril ameliorates endometriosis by inducing oxidative stress-mediated apoptosis in the wistar rat. J Mol Histol 56, 117 (2025). https://doi.org/10.1007/s10735-025-10397-4\nReceived:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s10735-025-10397-4","source_license":"public-domain-us","license_restricted":false}