Inflammasome-mediated cell death pathways in female reproductive disorders: from apoptosis, pyroptosis, and necroptosis to PANoptosis.
7 affiliations
- 1Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- 2Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
- 3Department of Medical Biology, Medical School, University of Pécs, Pécs, 7624, Hungary.
- 4János Szentágothai Research Centre, University of Pécs, Pécs, 7624, Hungary.
- 5Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. [email protected].
- 6Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. [email protected].
- 7Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. [email protected].
Abstract
Female reproductive disorders, including endometriosis, polycystic ovary syndrome (PCOS), preeclampsia (PE), recurrent pregnancy loss (RPL), premature ovarian insufficiency (POI), and implantation-related complications, are frequently associated with chronic inflammation, immune dysregulation, and impaired tissue homeostasis. Increasing evidence suggests that inflammasomes play central roles in regulating inflammatory responses and multiple forms of programmed cell death, including apoptosis, pyroptosis, necroptosis, and the recently described integrated cell death pathway known as PANoptosis. Inflammasome activation promotes the maturation of pro-inflammatory cytokines such as interleukin (IL)-1β and IL-18 and contributes to cellular and tissue injury through downstream cell death signaling pathways. Here, we review the existing knowledge on the molecular mechanisms linking inflammasome signaling to the regulated cell death pathways in female reproductive disorders. The role of apoptosis, pyroptosis and necroptosis in the pathogenesis of endometriosis, PCOS, PE, RPL, POI and other pregnancy related complications and the role of NLRP3 and other inflammasome complexes in disease progression are discussed. Recent studies suggest that crosstalk between these cell death pathways can lead to inflammatory pathology via PANoptosis-related mechanisms, although direct evidence for PANoptosis in reproductive diseases is still lacking. We also review current and potential therapeutic approaches targeting inflammasomes and associated cell death pathways such as NLRP3 inhibitors, IL-1β blockade and regulators of pyroptotic signaling. Together, the available evidence suggest that inflammasome-associated cell death pathways are important contributors to reproductive disease pathogenesis and may offer new diagnostic and therapeutic opportunities. Further mechanistic and clinical studies are needed to elucidate the role of PANoptosis and determine whether targeting key inflammasome and PANoptosis-related regulators can improve reproductive outcomes.
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BibTeX
@article{mardi2026inflammasomemediated,
title = {{Inflammasome-mediated cell death pathways in female reproductive disorders: from apoptosis, pyroptosis, and necroptosis to PANoptosis.}},
author = {Amirhossein Mardi and Hamid Ahmadi and Samaneh Abdolmohammadi-Vahid and Pouya Zahmatkesh and Golaleh Savari and Mohammad Sadegh Soltani-Zangbar and Leili Aghebati-Maleki},
journal = {Journal of ovarian research},
year = {2026},
month = jul,
doi = {10.1186/s13048-026-02221-8},
url = {https://europepmc.org/article/MED/42928293},
note = {CC BY},
}
RIS
TY - JOUR
TI - Inflammasome-mediated cell death pathways in female reproductive disorders: from apoptosis, pyroptosis, and necroptosis to PANoptosis.
AU - Amirhossein Mardi
AU - Hamid Ahmadi
AU - Samaneh Abdolmohammadi-Vahid
AU - Pouya Zahmatkesh
AU - Golaleh Savari
AU - Mohammad Sadegh Soltani-Zangbar
AU - Leili Aghebati-Maleki
PY - 2026
DA - 2026/07/29
JO - Journal of ovarian research
DO - 10.1186/s13048-026-02221-8
UR - https://europepmc.org/article/MED/42928293
AB - Female reproductive disorders, including endometriosis, polycystic ovary syndrome (PCOS), preeclampsia (PE), recurrent pregnancy loss (RPL), premature ovarian insufficiency (POI), and implantation-related complications, are frequently associated with chronic inflammation, immune dysregulation, and impaired tissue homeostasis. Increasing evidence suggests that inflammasomes play central roles in regulating inflammatory responses and multiple forms of programmed cell death, including apoptosis, pyroptosis, necroptosis, and the recently described integrated cell death pathway known as PANoptosis. Inflammasome activation promotes the maturation of pro-inflammatory cytokines such as interleukin (IL)-1β and IL-18 and contributes to cellular and tissue injury through downstream cell death signaling pathways. Here, we review the existing knowledge on the molecular mechanisms linking inflammasome signaling to the regulated cell death pathways in female reproductive disorders. The role of apoptosis, pyroptosis and necroptosis in the pathogenesis of endometriosis, PCOS, PE, RPL, POI and other pregnancy related complications and the role of NLRP3 and other inflammasome complexes in disease progression are discussed. Recent studies suggest that crosstalk between these cell death pathways can lead to inflammatory pathology via PANoptosis-related mechanisms, although direct evidence for PANoptosis in reproductive diseases is still lacking. We also review current and potential therapeutic approaches targeting inflammasomes and associated cell death pathways such as NLRP3 inhibitors, IL-1β blockade and regulators of pyroptotic signaling. Together, the available evidence suggest that inflammasome-associated cell death pathways are important contributors to reproductive disease pathogenesis and may offer new diagnostic and therapeutic opportunities. Further mechanistic and clinical studies are needed to elucidate the role of PANoptosis and determine whether targeting key inflammasome and PANoptosis-related regulators can improve reproductive outcomes.
SN - 1757-2215
ER -