Pyroptosis in the Pathogenesis of Common Gynecological Diseases

doi:10.12280/gjszjk.20250299

Abstract

Abstract:

Pyroptosis is an inflammatory form of programmed cell death. The abnormal activation or inhibition of pyroptosis is closely associated with the occurrence of inflammatory diseases, autoimmune diseases, and tumors in gynecology. For instance, in gynecological inflammatory diseases, pathogen infection can activate intracellular inflammasomes, trigger pyroptosis, and release a large number of inflammatory factors that exacerbate the inflammatory response, leading to tissue damage and disease progression. In gynecological tumors such as endometrial carcinoma and cervical cancer, pyroptosis may serve as a defensive mechanism for the body to eliminate tumor cells. However, tumor cells may also evade pyroptosis through certain mechanisms, promoting their own proliferation and metastasis. The role of pyroptosis is also important in pregnancy-related diseases. The in-depth study on the role of pyroptosis in common gynecological diseases can provide new insights and potential targets for early diagnosis and treatment of the diseases.

Key words: Pyroptosis, Genital diseases, female, Genital neoplasms, female, Abortion, habitual, Inflammasome, Gasdermins

HUANG Jing-ting, MA Li, YAO Bo, FENG Xiao-ling. Pyroptosis in the Pathogenesis of Common Gynecological Diseases[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(1): 71-76.

References 41

[1]	Black RA, Kronheim SR, Merriam JE, et al. A pre-aspartate-specific protease from human leukocytes that cleaves pro-interleukin-1 beta[J]. J Biol Chem, 1989, 264(10):5323-5326. doi: 10.1016/0167-4838(89)90081-2. pmid: 2784432
[2]	Cookson BT, Brennan MA. Pro-inflammatory programmed cell death[J]. Trends Microbiol, 2001, 9(3):113-114. doi: 10.1016/s0966-842x(00)01936-3. pmid: 11303500
[3]	Rao Z, Zhu Y, Yang P, et al. Pyroptosis in inflammatory diseases and cancer[J]. Theranostics, 2022, 12(9):4310-4329. doi: 10.7150/thno.71086. pmid: 35673561
[4]	Johnson DE, Cui Z. Triggering Pyroptosis in Cancer[J]. Biomolecules, 2025, 15(3):348. doi: 10.3390/biom15030348.
[5]	Wu J, Fernandes-Alnemri T, Alnemri ES. Involvement of the AIM2, NLRC4, and NLRP3 inflammasomes in caspase-1 activation by Listeria monocytogenes[J]. J Clin Immunol, 2010, 30(5):693-702. doi: 10.1007/s10875-010-9425-2. pmid: 20490635
[6]	Xu H, Yang J, Gao W, et al. Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome[J]. Nature, 2014, 513(7517):237-241. doi: 10.1038/nature13449.
[7]	Miao EA, Leaf IA, Treuting PM, et al. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria[J]. Nat Immunol, 2010, 11(12):1136-1142. doi: 10.1038/ni.1960. pmid: 21057511
[8]	Rühl S, Broz P. Caspase-11 activates a canonical NLRP3 inflammasome by promoting K+ efflux[J]. Eur J Immunol, 2015, 45(10):2927-2936. doi: 10.1002/eji.201545772.
[9]	Evavold CL, Hafner-Bratkovic I, Devant P, et al. Control of gasdermin D oligomerization and pyroptosis by the Ragulator-Rag-mTORC1 pathway[J]. Cell, 2021, 184(17):4495-4511.e19. doi: 10.1016/j.cell.2021.06.028 pmid: 34289345
[10]	Orzalli MH, Prochera A, Payne L, et al. Virus-mediated inactivation of anti-apoptotic Bcl-2 family members promotes Gasdermin-E-dependent pyroptosis in barrier epithelial cells[J]. Immunity, 2021, 54(7):1447-1462.e5. doi: 10.1016/j.immuni.2021.04.012. pmid: 33979579
[11]	中华医学会妇产科学分会感染性疾病协作组. 外阴阴道假丝酵母菌病中国诊治指南(2024版)[J]. 中华妇产科杂志, 2024, 59(7):499-504. doi: 10.3760/cma.j.cn112141-20240326-00185.
[12]	Peng Y, Xu Y, Li S, et al. Mechanism of Vaginal Epithelial Cell Pyroptosis Induced by the NLRP3 Inflammasome in Vulvovaginal Candidiasis[J]. Am J Reprod Immunol, 2024, 92(1):e13893. doi: 10.1111/aji.13893.
[13]	Jafarzadeh A, Nemati M, Salarkia E, et al. Inflammatory responses during trichomoniasis: The role of Toll-like receptors and inflammasomes[J]. Parasite Immunol, 2023, 45(8):e13000. doi: 10.1111/pim.13000.
[14]	中华医学会妇产科学分会感染性疾病协作组. 阴道毛滴虫病诊治指南(2021修订版)[J]. 中华妇产科杂志, 2021, 56(1):7-10. doi: 10.3760/cma.j.cn112141-20200717-00582.
[15]	Yao Q, Lin D, Yang Y, et al. Combination of Doxycycline with Metronidazole Protects against Pyroptosis in Rats with Endometritis through the Modulation of TLR4/NF-κB Pathway[J]. Discov Med, 2024, 36(180):140-149. doi: 10.24976/Discov.Med.202436180.13.
[16]	Xiong S, Xu C, Yang C, et al. FuKe QianJin capsule alleviates endometritis via inhibiting inflammation and pyroptosis through modulating TLR4/ NF-κB /NLRP3 pathway[J]. J Ethnopharmacol, 2025, 337(Pt 3):118962. doi: 10.1016/j.jep.2024.118962.
[17]	Taravat M, Asadpour R, Jozani RJ, et al. Enhanced anti-inflammatory effect of Rosmarinic acid by encapsulation and combination with the exosome in mice with LPS-induced endometritis through suppressing the TLR4-NLRP3 signaling pathway[J]. J Reprod Immunol, 2023, 159:103992. doi: 10.1016/j.jri.2023.103992.
[18]	Li L, Qi J, Tao H, et al. Protective effect of the total flavonoids from Clinopodium chinense against LPS-induced mice endometritis by inhibiting NLRP3 inflammasome-mediated pyroptosis[J]. J Ethnopharmacol, 2023, 312:116489. doi: 10.1016/j.jep.2023.116489.
[19]	Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis[J]. BMJ, 2022, 379:e070750. doi: 10.1136/bmj-2022-070750.
[20]	Guo Q, Zhou C, Xiang Y, et al. Pyroptosis orchestrates immune responses in endometriosis[J]. Int Immunopharmacol, 2023, 118:110141. doi: 10.1016/j.intimp.2023.110141.
[21]	An M, Fu X, Meng X, et al. PI3K/AKT signaling pathway associates with pyroptosis and inflammation in patients with endometriosis[J]. J Reprod Immunol, 2024, 162:104213. doi: 10.1016/j.jri.2024.104213.
[22]	Du X, Yang H, Kang X, et al. Blocking GATA6 Alleviates Pyroptosis and Inhibits Abdominal Wall Endometriosis Lesion Growth Through Inactivating the PI3K/AKT Pathway[J]. Cell Biochem Biophys, 2025, 83(2):1757-1770. doi: 10.1007/s12013-024-01583-4.
[23]	Zhang M, Shi Z, Peng X, et al. NLRP3 inflammasome-mediated Pyroptosis induce Notch signal activation in endometriosis angiogenesis[J]. Mol Cell Endocrinol, 2023, 574:111952. doi: 10.1016/j.mce.2023.111952.
[24]	Huang Y, Jiang Y, Ji H, et al. CHS-Ⅳa activates the IGF1R/PI3K signal pathway with inhibited pyroptosis of endometrial stromal cells and progress of endometriosis[J]. Int Immunopharmacol, 2024, 143(Pt 3):113527. doi: 10.1016/j.intimp.2024.113527.
[25]	Xu K, Zhang M, Zou X, et al. Tetramethylpyrazine Confers Protection Against Oxidative Stress and NLRP3-Dependent Pyroptosis in Rats with Endometriosis[J]. Organogenesis, 2025, 21(1):2460261. doi: 10.1080/15476278.2025.2460261.
[26]	Lin Y, Zhang Y, Ding X, et al. Chlorogenic acid mitigates DHEA-induced oxidative stress in granulosa cells and alleviates ferroptosis via the NF-κB signaling pathway in PCOS[J]. Eur J Pharmacol, 2025, 1002:177870. doi: 10.1016/j.ejphar.2025.177870.
[27]	Chamanara S, Hozouri V, Irandoost E. Inhibition of NLRP3 inflammasome-A potential mechanistic therapeutic for treatment of polycystic ovary syndrome?[J]. J Biochem Mol Toxicol, 2024, 38(1):e23592. doi: 10.1002/jbt.23592.
[28]	Chen J, Zhu Z, Xu S, et al. HDAC1 participates in polycystic ovary syndrome through histone modification by regulating H19/miR-29a-3p/NLRP3-mediated granulosa cell pyroptosis[J]. Mol Cell Endocrinol, 2023, 573:111950. doi: 10.1016/j.mce.2023.111950.
[29]	Huang Q, Li Y, Chen Z, et al. Bushenhuoluo Decoction improves polycystic ovary syndrome by regulating exosomal miR-30a-5p/SOCS3/mTOR/NLRP3 signaling-mediated autophagy and pyroptosis[J]. J Ovarian Res, 2024, 17(1):29. doi: 10.1186/s13048-024-01355-x. pmid: 38302986
[30]	Zhang Y, Xie X, Ma Y, et al. Cyproterone Acetate Mediates IRE1α Signaling Pathway to Alleviate Pyroptosis of Ovarian Granulosa Cells Induced by Hyperandrogen[J]. Biology(Basel), 2022, 11(12):1761. doi: 10.3390/biology11121761.
[31]	Li K, Qiu J, Pan J, et al. Pyroptosis and Its Role in Cervical Cancer[J]. Cancers(Basel), 2022, 14(23):5764. doi: 10.3390/cancers14235764.
[32]	Chen J, Ge L, Shi X, et al. Lobaplatin Induces Pyroptosis in Cervical Cancer Cells via the Caspase-3/GSDME Pathway[J]. Anticancer Agents Med Chem, 2022, 22(11):2091-2097. doi: 10.2174/1871520621666211018100532.
[33]	Zhang W, Liu C, Li J, et al. Tanshinone IIA: New Perspective on the Anti-Tumor Mechanism of A Traditional Natural Medicine[J]. Am J Chin Med, 2022, 50(1):209-239. doi: 10.1142/S0192415X22500070.
[34]	Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3):209-249. doi: 10.3322/caac.21660.
[35]	Guo H, Qin W, Li J, et al. Cell-type-specific regulators landscape and regulatory mechanisms underlying pyroptosis in uterine corpus endometrial carcinoma[J]. J Cancer, 2025, 16(2):660-679. doi: 10.7150/jca.100547. pmid: 39744500
[36]	Su P, Mao X, Ma J, et al. ERRα promotes glycolytic metabolism and targets the NLRP3/caspase-1/GSDMD pathway to regulate pyroptosis in endometrial cancer[J]. J Exp Clin Cancer Res, 2023, 42(1):274. doi: 10.1186/s13046-023-02834-7. pmid: 37864196
[37]	Liu ZS, Jing CL. A novel risk prediction model of pyroptosis-related genes for the prognosis and immunotherapy response of endometrial cancer[J]. Eur Rev Med Pharmacol Sci, 2022, 26(7):2259-2278. doi: 10.26355/eurrev_202204_28456.
[38]	Wang J, Nuray U, Yan H, et al. Pyroptosis is involved in the immune microenvironment regulation of unexplained recurrent miscarriage[J]. Mamm Genome, 2024, 35(2):256-279. doi: 10.1007/s00335-024-10038-3.
[39]	Zhu D, Zou H, Liu J, et al. Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation[J]. Front Immunol, 2021, 12:782792. doi: 10.3389/fimmu.2021.782792.
[40]	Zhu X, Xu K, Ai S, et al. miR-126-5p protects from URSA via inhibiting Caspase-1-dependent pyroptosis of trophoblast cells[J]. Cell Mol Life Sci, 2025, 82(1):204. doi: 10.1007/s00018-025-05713-w. pmid: 40372489
[41]	Popli P, Oestreich AK, Maurya VK, et al. The autophagy protein ATG14 safeguards against unscheduled pyroptosis activation to enable embryo transport during early pregnancy[J]. Elife, 2025,13:RP97325. doi: 10.7554/eLife.97325.