Sulforaphane ameliorates endometriosis in rats by modulating autophagy and mitochondrial dysfunction

In: Molecular & Cellular Toxicology · 2025 · doi:10.1007/s13273-025-00570-x · W4414113054
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Sulforaphane inhibited endometriosis lesion growth in rats by downregulating VEGF, upregulating apoptosis, and modulating autophagy and mitochondrial dysfunction in endometrial stromal cells.

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The study investigated whether sulforaphane (SFN) ameliorates endometriosis in a rat model generated by autotransplantation, using dose-ranging SFN administration alongside measurements of lesion volume/weight, histopathology (HE staining), VEGF and apoptosis-related proteins (Western blot), and autophagy proteins (immunofluorescence). SFN inhibited lesion growth in a dose-dependent manner, reduced endometrial pathological changes, downregulated VEGF, and increased apoptosis in endometrial tissues and in rat endometrial stromal cells (ESCs), where it also decreased cell viability, migration, and invasion while disrupting mitochondrial function; SFN effects were concentration-dependent. Mechanistically, SFN altered autophagy-related proteins and inhibited autophagic flux, and the autophagic flux inhibitor chloroquine showed that autophagy inhibition also impaired ESC phenotypes and mitochondrial function, with combined SFN and chloroquine producing synergistic effects. The paper does not explicitly discuss limitations such as sample size, blinding/randomization, or whether findings translate to humans. This paper is centrally about endometriosis — it tests SFN treatment in rats and links its effects to autophagy modulation and mitochondrial dysfunction.

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Abstract

Objective The aim of this study was to investigate the role and mechanism of Sulforaphane (SFN) in ameliorating endometriosis (EMs).

Methods

EMs’ rat model was established by autotransplantation method and administered with low, medium, and high doses of SFN. The volume and weight of the lesions were measured, the histopathological changes of the endometrium were observed by HE staining, and autophagy proteins were detected by immunofluorescence staining, whereas VEGF and apoptosis-related proteins were detected by Western blot. Rat primary endometrial stromal cells (ESCs) were isolated. Cell viability was determined by MTT, apoptosis by Tunel, migration and invasion by Transwell, and apoptotic and autophagic proteins by Western blot. Mitochondrial membrane potential, ATP content, and ROS levels were assessed for cellular mitochondrial function. Chloroquine (CQ), an autophagic flux inhibitor (AFI), was used alone or in combination with SFN to intervene cells.

Results

SFN inhibited the growth of EMs rat lesions in a dose-dependent pattern, alleviated the pathological changes of endometrium, downregulated VEGF, and upregulated apoptosis in endometrial tissues. Different concentrations of SFN effectively inhibited cell viability, migration, and invasion, and promoted apoptosis in rat ESCs, and the effects were concentration-dependent. SFN regulated autophagy proteins and inhibited autophagic flux. SFN disrupted the mitochondrial function of ESCs. CQ intervention alone inhibited ESCs cell viability, migration, and invasion, promoted apoptosis, and disrupted cellular mitochondrial function. Combined CQ intervention had a synergistic effect on SFN in regulating the biological phenotype and mitochondrial function of ESCs.

Conclusion

SFN ameliorates EMs in rats by modulating autophagy and mitochondrial dysfunction. Similar content being viewed by others Availability of data and materials The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

References

Allaire C, Bedaiwy MA, Yong PJ (2023) Diagnosis and management of endometriosis. CMAJ 195(10):E363–E371 Allavena G, Carrarelli P, Del Bello B, Luisi S, Petraglia F, Maellaro E (2015) Autophagy is upregulated in ovarian endometriosis: a possible interplay with p53 and heme oxygenase-1. Fertil Steril 103(5):1244–51.e1 Aparicio R, Hansen M, Walker DW, Kumsta C (2020) The selective autophagy receptor SQSTM1/p62 improves lifespan and proteostasis in an evolutionarily conserved manner. Autophagy 16(4):772–774 Brichant G, Laraki I, Henry L, Munaut C, Nisolle M (2021) New therapeutics in endometriosis: a review of hormonal, non-hormonal, and non-coding RNA treatments. Int J Mol Sci. https://doi.org/10.3390/ijms221910498 Bulun SE, Yilmaz BD, Sison C, Miyazaki K, Bernardi L, Liu S et al (2019) Endometriosis. Endocr Rev 40(4):1048–1079 Chapron C, Marcellin L, Borghese B, Santulli P (2019) Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol 15(11):666–682 Chen Q, Zhou Y, Yu M, Zhu S, Sun J, Du W et al (2024) Transcription factor EB-mediated autophagy affects cell migration and inhibits apoptosis to promote endometriosis. Apoptosis 29(5–6):757–767 Debnath J, Gammoh N, Ryan KM (2023) Autophagy and autophagy-related pathways in cancer. Nat Rev Mol Cell Biol 24(8):560–575 Elkashty OA, Tran SD (2021) Sulforaphane as a promising natural molecule for cancer prevention and treatment. Curr Med Sci 41(2):250–269 Esfandyari S, Aleyasin A, Noroozi Z, Taheri M, Khodarahmian M, Eslami M et al (2021) The protective effect of sulforaphane against oxidative stress through activation of NRF2/ARE pathway in human granulosa cells. Cell J 23(6):692–700 Ham J, Song J, Song G, Lim W (2024) Autophagy regulation and redox perturbation by transcrocetin suppress the growth of endometriosis. Biomed Pharmacother 173:116284 Harrath AH, Rahman MA, Bhajan SK, Bishwas AK, Rahman MDH, Alwasel S et al (2024) Autophagy and female fertility: mechanisms, clinical implications, and emerging therapies. Cells 13(16) Horne AW, Missmer SA (2022) Pathophysiology, diagnosis, and management of endometriosis. BMJ 379:e070750 Hu Y, Zhou Y, Yang G, Wang Y, Zheng Z, Li J et al (2018) Sulforaphane-N-acetyl-cysteine inhibited autophagy leading to apoptosis via Hsp70-mediated microtubule disruption. Cancer Lett 431:85–95 Hung SW, Zhang R, Tan Z, Chung JPW, Zhang T, Wang CC (2021) Pharmaceuticals targeting signaling pathways of endometriosis as potential new medical treatment: a review. Med Res Rev 41(4):2489–2564 Jo C, Kim S, Cho SJ, Choi KJ, Yun SM, Koh YH et al (2014) Sulforaphane induces autophagy through ERK activation in neuronal cells. FEBS Lett 588(17):3081–3088 Kamal MM, Akter S, Lin CN, Nazzal S (2020) Sulforaphane as an anticancer molecule: mechanisms of action, synergistic effects, enhancement of drug safety, and delivery systems. Arch Pharm Res 43(4):371–384 Kapoor R, Sirohi VK, Gupta K, Dwivedi A (2019) Naringenin ameliorates progression of endometriosis by modulating Nrf2/Keap1/HO1 axis and inducing apoptosis in rats. J Nutr Biochem 70:215–226 Kapoor R, Stratopoulou CA, Dolmans MM (2021) Pathogenesis of endometriosis: new insights into prospective therapies. Int J Mol Sci. https://doi.org/10.3390/ijms222111700 Khashchenko EP, Vysokikh MY, Marey MV, Sidorova KO, Manukhova LA, Shkavro NN et al (2024) Altered glycolysis, mitochondrial biogenesis, autophagy and apoptosis in peritoneal endometriosis in adolescents. Int J Mol Sci. https://doi.org/10.3390/ijms25084238 Kobayashi H, Imanaka S, Yoshimoto C, Matsubara S, Shigetomi H (2024) Molecular mechanism of autophagy and apoptosis in endometriosis: current understanding and future research directions. Reprod Med Biol 23(1):e12577 Kvaskoff M, Mu F, Terry KL, Harris HR, Poole EM, Farland L, Missmer SA (2015) Endometriosis: a high-risk population for major chronic diseases? Hum Reprod Update 21(4):500–516 Li D, Shao R, Wang N, Zhou N, Du K, Shi J et al (2021) Sulforaphane activates a lysosome-dependent transcriptional program to mitigate oxidative stress. Autophagy 17(4):872–887 Li Y, An M, Fu X, Meng X, Ma Y, Liu H et al (2023) Bushen wenyang huayu decoction inhibits autophagy by regulating the SIRT1-FoXO-1 pathway in endometriosis rats. J Ethnopharmacol 308:116277 Liu Y, Zhang Z, Lu X, Meng J, Qin X, Jiang J (2020) Anti-nociceptive and anti-inflammatory effects of sulforaphane on sciatic endometriosis in a rat model. Neurosci Lett 723:134858 Lu Y, Zhang Y, Lou Y, Cui W, Miao L (2020) Sulforaphane suppresses obesity-related glomerulopathy-induced damage by enhancing autophagy via Nrf2. Life Sci 258:118153 Lu Z, Ren Y, Yang L, Jia A, Hu Y, Zhao Y et al (2021) Inhibiting autophagy enhances sulforaphane-induced apoptosis via targeting NRF2 in esophageal squamous cell carcinoma. Acta Pharm Sin B 11(5):1246–1260 Mangla B, Javed S, Sultan MH, Kumar P, Kohli K, Najmi A et al (2021) Sulforaphane: a review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials. Phytother Res 35(10):5440–5458 Mordecai J, Ullah S, Ahmad I (2023) Sulforaphane and its protective role in prostate cancer: a mechanistic approach. Int J Mol Sci. https://doi.org/10.3390/ijms24086979 Nezhat F, Datta MS, Hanson V, Pejovic T, Nezhat C, Nezhat C (2008) The relationship of endometriosis and ovarian malignancy: a review. Fertil Steril 90(5):1559–1570 Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148(6):1145–1159 Otoo RA, Allen AR (2023) Sulforaphane’s multifaceted potential: from neuroprotection to anticancer action. Molecules. https://doi.org/10.3390/molecules28196902 Pang C, Wu Z, Xu X, Yang W, Wang X, Qi Y (2021) Paeonol alleviates migration and invasion of endometrial stromal cells by reducing HIF-1α-regulated autophagy in endometriosis. Front Biosci (Landmark Ed) 26(9):485–495 Park S, Ham J, Yang C, Park W, Park H, An G et al (2023) Melatonin inhibits endometriosis development by disrupting mitochondrial function and regulating tiRNAs. J Pineal Res 74(1):e12842 Peng ZT, Gu P (2021) Sulforaphane suppresses autophagy during the malignant progression of gastric carcinoma via activating miR-4521/PIK3R3 pathway. Hum Exp Toxicol 40(12_suppl):S711–S720 Pizzimenti C, Fiorentino V, Ruggeri C, Franchina M, Ercoli A, Tuccari G, Ieni A (2024) Autophagy involvement in non-neoplastic and neoplastic endometrial pathology: the state of the art with a focus on carcinoma. Int J Mol Sci. https://doi.org/10.3390/ijms252212118 Saunders PTK, Horne AW (2021) Endometriosis: etiology, pathobiology, and therapeutic prospects. Cell 184(11):2807–2824 Taylor HS, Kotlyar AM, Flores VA (2021) Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet 397(10276):839–852 Treasure K, Harris J, Williamson G (2023) Exploring the anti-inflammatory activity of sulforaphane. Immunol Cell Biol 101(9):805–828 Vanduchova A, Anzenbacher P, Anzenbacherova E (2019) Isothiocyanate from broccoli, sulforaphane, and its properties. J Med Food 22(2):121–126 Vernon MW, Wilson EA (1985) Studies on the surgical induction of endometriosis in the rat. Fertil Steril 44(5):684–694 Wang S, Wang Y, Liu X, Yang Y, Wu S, Liu Y (2022) SFN enhanced the radiosensitivity of cervical cancer cells via activating LATS2 and blocking Rad51/MDC1 recruitment to DNA damage site. Cancers (Basel). https://doi.org/10.3390/cancers14081872 Yang HL, Mei J, Chang KK, Zhou WJ, Huang LQ, Li MQ (2017) Autophagy in endometriosis. Am J Transl Res 9(11):4707–4725 Zhan L, Li J, Wei B (2018) Autophagy in endometriosis: friend or foe? Biochem Biophys Res Commun 495(1):60–63 Zheng K, Ma J, Wang Y, He Z, Deng K (2020) Sulforaphane inhibits autophagy and induces exosome-mediated paracrine senescence via regulating mTOR/TFE3. Mol Nutr Food Res 64(14):e1901231 Zhou A, Hong Y, Lv Y (2019) Sulforaphane attenuates endometriosis in rat models through inhibiting PI3K/Akt signaling pathway. Dose Response 17(2):1559325819855538 Zhou Y, Zhao X, Zhang L, Xia Q, Peng Y, Zhang H et al (2022) Iron overload inhibits cell proliferation and promotes autophagy via PARP1/SIRT1 signaling in endometriosis and adenomyosis. Toxicology 465:153050

Acknowledgements

Not applicable. Funding Not applicable. Author information Authors and Affiliations Contributions DongMei Pang designed the research study. DongMei Pang performed the research. MouChang Qiu and FeiFei Xu provided help and advice. MouChang Qiu and FeiFei Xu analyzed the data. DongMei Pang wrote the manuscript. DongMei Pang reviewed and edited the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. Corresponding author Ethics declarations Competing interests DongMei Pang, MouChang Qiu and FeiFei Xu declare that they have no conflict of interest. Ethical statement All animal experiments were complied with the ARRIVE guidelines and performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The experiments were approved by the Institutional Animal Care and Use Committee of The Affiliated Taizhou People’s Hospital of Nanjing Medical University. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer 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. About this article Cite this article Pang, D., Qiu, M. & Xu, F. Sulforaphane ameliorates endometriosis in rats by modulating autophagy and mitochondrial dysfunction. Mol. Cell. Toxicol. (2025). https://doi.org/10.1007/s13273-025-00570-x Received: Revised: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s13273-025-00570-x

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