Tissue Specific Necroptosis in the Cervix, Uterus, and Placenta in an LPS-induced Preterm Birth Model.

Preterm birth remains a preventable cause of death for both mothers and infants. However, due to its association with numerous biological mechanisms, its underlying processes remain poorly understood. Although components of the PANoptotic pathway have garnered increasing interest, particularly over the past decade, the literature concerning their role in preterm birth and pregnancy is still limited. To contribute to the understanding of mechanisms, we aimed to investigate the relationship between preterm birth and necroptosis markers such as receptor-interacting protein kinase-3 (RIPK3/RIP3) and mixed lineage kinase domain-like pseudokinase (MLKL) in the cervix, uterus, and placental tissues using lipopolysaccharide (LPS)-induced preterm birth model. Our objective was to determine the expression levels of RIPK3 and MLKL, explore their association with inflammation, assess how their levels change during preterm birth, and examine the potential role of Necrostatin-1 (NEC-1) in this mechanism. Our findings suggest that necroptosis is a component of LPS-mediated preterm birth, with RIPK3 and MLKL proteins being differentially expressed across the uterus, cervix, and placenta. The data indicate that necroptosis may be activated by distinct proteins depending on the reproductive tissue. Furthermore, the LPS-induced depletion of MLKL in the amniotic membrane suggests that this protein may play a key role in preterm membrane rupture, warranting further investigation. Although it is evident that the necroptosis pathway in preterm birth is a complex process which requires additional studies for complete elucidation, we believe that the results of our study will provide a foundation for future research in this area.