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NRF2 protects against ROS-induced preterm premature rupture of membranes through regulation of mitochondria †
Biol Reprod. 2023 Jul 10:ioad075. doi: 10.1093/biolre/ioad075. Online ahead of print.ABSTRACTPreterm premature rupture of membranes (pPROM) is a major cause of preterm birth and neonatal mortality. Reactive oxygen species (ROS) have been identified as a critical factor in the development of pPROM. Mitochondria are known to be the primary source of ROS and play a vital role in maintaining cellular function. The Nuclear erythroid 2-related factor 2 (NRF2) has been demonstrated to play a crucial role in regulating mitochondrial function. However, research exploring the impact of NRF2-regulated mitochondria on pPROM is limited...
Source: Reproductive Biology - July 10, 2023 Category: Reproduction Medicine Authors: Xinyuan Zhang Xiao He Linna Wei Yang He Yunlong Li Yingxiong Wang Chunli Li Source Type: research

GIT2 deficiency attenuates inflammation induced expression of pro-labor mediators in human amnion and myometrial cells.
Abstract Untimely activation of the inflammatory response by sterile or infective insults in uterine tissues can result in preterm birth. Pro-inflammatory cytokines and pathogenic activation of toll-like receptors (TLRs) initiates a biochemical cascade of events leading to myometrial activation and contractility, cervical dilatation, and rupture of the chorioamniotic membranes. GIT2 is a signaling protein known to play a role in innate and adaptive immunity; however, its role in the inflammatory pathways of human labor are not known. In this article, we report that GIT2 expression is lower in human myometrium and ...
Source: Reproductive Biology - March 26, 2019 Category: Reproduction Medicine Authors: Lim R, Lappas M Tags: Biol Reprod Source Type: research

IRF5 is increased in labouring myometrium and regulates pro-labour mediators
Preterm birth continues to be the leading cause of neonatal mortality and morbidities that can extend into adult life. Few treatment options stem from our incomplete understanding of the mechanisms of human labour and delivery. Activation of the inflammatory response in gestational tissues by inflammation and/or infection leads to the production of pro-inflammatory and pro-labour mediators, thus preterm birth. Interferon regulatory factor 5 (IRF5) has recently emerged as an important pro-inflammatory transcription factor involved in acute and chronic inflammation. The aims of this study were to determine the expression of ...
Source: Reproduction - August 17, 2018 Category: Reproduction Medicine Authors: Lim, R., Barker, G., Lappas, M. Tags: Research Source Type: research

PARK7 regulates inflammation-induced pro-labour mediators in myometrial and amnion cells
Preterm birth is a prevalent cause of neonatal deaths worldwide. Inflammation has been implicated in spontaneous preterm birth involved in the processes of uterine contractility and membrane rupture. Parkinson protein 7 (PARK7) has been found to play an inflammatory role in non-gestational tissues. The aims of this study were to determine the expression of PARK7 in myometrium and fetal membranes with respect to term labour onset and to elucidate the effect of PARK7 silencing in primary myometrium and amnion cells on pro-inflammatory and pro-labour mediators. PARK7 mRNA expression was higher in term myometrium and fetal mem...
Source: Reproduction - January 22, 2018 Category: Reproduction Medicine Authors: Lim, R., Barker, G., Lappas, M. Tags: Research Source Type: research

The IL-1 β signalling pathway and its role in regulating pro-inflammatory and pro-labour mediators in human primary myometrial cells.
This study sought to determine the role of the adaptor proteins myeloid differentiation primary response 88 (MyD88), tumour necrosis factor receptor-associated factor 6 (TRAF6), IL-1 receptor-associated kinase 4 (IRAK4) and transforming growth factor beta-activated kinase 1 (TAK1) in IL-1β-induced formation of pro-inflammatory and pro-labour mediators in human myometrium. Human primary myometrial cells were transfected with siRNA against MyD88 (siMYD88), TRAF6 (siTRAF6), IRAK4 (siIRAK4) or TAK1 (siTAK1), treated with IL-1β, and assayed for the mRNA expression and or secretion of pro-inflammatory and pro-labour mediators....
Source: Reproductive Biology - October 6, 2017 Category: Reproduction Medicine Authors: Lappas M Tags: Reprod Biol Source Type: research

RKIP is decreased in laboring myometrium and modulates inflammation-induced pro-labor mediators
In conclusion, in human primary myometrial cells, RKIP negatively regulates IL1B- and TNF-induced expression and or secretion of pro-inflammatory and pro-labor mediators by inhibiting NF-B RELA activation.
Source: Reproduction - March 8, 2017 Category: Reproduction Medicine Authors: Lappas, M. Tags: Research Source Type: research

A Novel Role for SIRT3 in Regulating Mediators Involved in the Terminal Pathways of Human Labor and Delivery.
In this study, we determined the effect of term labor and pro-inflammatory cytokines on SIRT3, SIRT4, SIRT5 and SIRT7 expression in human myometrium. Functional studies were also employed to investigate the effect of siRNA knockdown of SIRTs in regulating inflammation-induced pro-labor mediators. Western blot analysis and qRT-PCR were used to determine SIRT3, SIRT4, SIRT5 and SIRT7 mRNA and protein expression in human myometrium. siRNA knockdown of SIRT3 in myometrial primary cells determined its role in response to inflammatory stimuli IL1B and TNF. SIRT3 mRNA and protein expression were significantly lower in term labori...
Source: Biology of Reproduction - September 13, 2016 Category: Reproduction Medicine Authors: Lim R, Barker G, Menon R, Lappas M Tags: Biol Reprod Source Type: research

Optineurin suppression activates the mediators involved in the terminal effector pathways of human labour and delivery.
Abstract Spontaneous preterm birth remains the major cause of neonatal death and morbidity. Studies in non-gestational tissues report that optineurin (OPTN) is critical in the termination of NFKB1 activity and control of inflammation, central features of spontaneous preterm birth. The aims of the present study were to determine: (1) OPTN expression in fetal membranes and the myometrium during labour; (2) the effects of IL1B on OPTN expression in primary myometrial cells; and (3) the effects of OPTN short interference (si) RNA on IL1B-stimulated proinflammatory and prolabour mediators. OPTN mRNA and protein express...
Source: Reproduction, Fertility, and Development - May 1, 2016 Category: Reproduction Medicine Authors: Lim R, Barker G, Lappas M Tags: Reprod Fertil Dev Source Type: research

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