Table 2.
Representative studies investigating regulated cell death pathways in female reproductive disorders
| Disorder | Experimental model | Cell death pathway | Key molecular mediators | Principal findings | Level of evidence | Study (Ref.) |
|---|---|---|---|---|---|---|
| Endometriosis | Human endometriotic tissues | Pyroptosis | NLRP3, Caspase-1, IL-1β | Demonstrated activation of the NLRP3/caspase-1/IL-1β axis in endometriosis. | Human | [106] |
| Endometriosis | LPS-induced mouse endometritis + primary endometrial epithelial cells | Pyroptosis | TLR4, NF-κB, NLRP3 | TFC inhibited inflammasome activation and pyroptosis. | Animal + in vitro | [110] |
| Endometriosis | Mouse model | Pyroptosis | NLRP3, Autophagy | Melatonin attenuated endometritis through inhibition of NLRP3 activation. | Animal | [111] |
| PCOS | Human transcriptomic dataset | Necroptosis | IL-33, BCL2, TNFSF10 | Established a necroptosis-related risk signature for PCOS. | Human (bioinformatics) | [112] |
| PCOS | Testosterone-induced mouse model + granulosa cells | Pyroptosis | NLRP3, Caspase-1, GSDMD | Hyperandrogenism activated NLRP3-mediated pyroptosis. | Animal + Human + in vitro | [113] |
| PE | HTR8/SVneo cells + placental tissues | Apoptosis | IFN-γ, JAK1, STAT1, SOCS1 | IFN-γ impaired trophoblast invasion through JAK1/STAT1 activation. | Human + in vitro | [114] |
| PE | Human placentas + hypoxic trophoblasts | Necroptosis | RIPK1, RIPK3, MLKL, SIRT3 | Necroptosis contributed to trophoblast dysfunction in PE. | Human + in vitro | [115] |
| RPL | Human serum and placenta | Pyroptosis | NLRP3, Caspase-1, IL-18 | Increased inflammasome activation in women with RPL. | Human | [116] |
| RPL | Murine spontaneous abortion model | Pyroptosis | AIM2, ASC, Caspase-1, NLRP3 | Inflammasome activation associated with fetal loss. | Animal | [117] |
| POI | Cyclophosphamide-induced mouse model | Pyroptosis | NLRP3, GSDMD | Leonurine hydrochloride alleviated ovarian injury by suppressing pyroptosis. | Animal | [118] |
| POI | Mouse model | Proposed PANoptosis | NLRP3, RIPK3, CASP8 | Suppressed molecular signatures consistent with PANoptosis; canonical PANoptosome not confirmed. | Animal (emerging evidence) | [119] |
Abbreviations: PCOS Polycystic ovary syndrome, PE Preeclampsia, RPL Recurrent pregnancy loss, Premature ovarian insufficiency (POI); JAK1 Janus Kinase 1, BCL-2 Pro-apoptotic members of the B-cell lymphoma 2, GSDMD Gasdermin D, IL-1β interleukin-1β, IL-18 interleukin-18, NLRP3 NOD-, LRR-, and pyrin domain-containing protein 3, STAT1 Signal Transducer and Activator of Transcription 1, RIPK1 receptor-interacting protein kinase 1, MLKL Mixed Lineage Kinase Domain-Like, NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells, IFNγ Interferon γ, MAPK Mitogen-Activated Protein Kinase