Expression and Clinical Significance of NOD-Like Receptor Protein 3 (NLRP3) and Caspase-1 in Fetal Membrane and Placental Tissues of Patients with Premature Rupture of Membrane

Zhu, Jinming; He, Miao; Ma, Chunling; Peng, Fengyun; Su, Yu‐Li; Huang, Lei

doi:10.12659/msm.906157

Cited by 5 publications

(4 citation statements)

References 12 publications

(11 reference statements)

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“…Similarly, KEGG pathway enrichment analysis for upregulated genes in the amnion included three inflammatory pathways: cytokine-cytokine interaction, TNF signaling and the CXCL family. These findings are consistent with previous studies which have described dysregulation of cytokines and chemokines to be involved in PPROM [ 29 – 31 ], and confirm that both layers of the fetal membrane are targets of inflammatory pathway dysregulation during PPROM. Interestingly, neither KEGG pathways nor gene ontology enrichment analyses identified any pathways enriched for down-regulated genes in the chorion.…”

Section: Discussionsupporting

confidence: 93%

Transcriptomic analysis delineates preterm prelabor rupture of membranes from preterm labor in preterm fetal membranes

Underhill,

Mennella,

Tollefson

et al. 2024

BMC Med Genomics

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Background Globally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not occur simultaneously: preterm labor and preterm prelabor rupture of membranes (PPROM). To further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events, we compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with PPROM deliveries. We hypothesized that the fetal membrane tissue from preterm labor with PPROM cases will have an RNA-seq profile divergent from the fetal membrane tissue from preterm labor controls. Methods Chorioamnion, separated into amnion and chorion, was collected from eight gestationally age-matched cases and controls within 15 min of birth, and analyzed using RNA sequencing. Pathway enrichment analyses and functional annotations of differentially expressed genes were performed using KEGG and Gene Ontogeny Pathway enrichment analyses. Results A total of 1466 genes were differentially expressed in the amnion, and 484 genes were differentially expressed in the chorion (log2 fold change > 1, FDR < 0.05) in cases (preterm labor with PPROM), versus controls (preterm labor only). In the amnion, the most significantly enriched (FDR < 0.01) KEGG pathway among down-regulated genes was the extracellular matrix receptor interaction pathway. Seven of the most significantly enriched pathways were comprised of multiple genes from the COL family, including COL1A, COL3A1, COL4A4, and COL4A6. In the chorion, the most significantly enriched KEGG pathways in up-regulated genes were chemokine, NOD receptor, Toll-like receptor, and cytokine-cytokine receptor signaling pathways. Similarly, KEGG pathway enrichment analysis for up-regulated genes in the amnion included three inflammatory pathways: cytokine-cytokine interaction, TNF signaling and the CXCL family. Six genes were significantly up regulated in chorionic tissue discriminated between cases (preterm labor with PPROM) and controls (preterm labor only) including GBP5, CXCL9, ALPL, S100A8, CASP5 and MMP25. Conclusions In our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.

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Section: Discussionsupporting

confidence: 93%

Transcriptomic analysis delineates preterm prelabor rupture of membranes from preterm labor in preterm fetal membranes

Underhill,

Mennella,

Tollefson

et al. 2024

BMC Med Genomics

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“…In our study, we report a significant increase in mRNA expression for CASP1 in FGR compared to control pregnancies. These findings are supported by studies that show that CASP1 is detected, and its expression levels increased, in placentae from premature rupture of membrane (PROM) patients [68], women with a high BMI [69], and preeclamptic women [53], all of which are associated with inflammation. Furthermore, Brien et al (2017) report decreased expression of IL-6 and IL-1β following CASP1 inhibition in monosodium urate crystal-induced inflammation in human term placentae [48].…”

Section: Discussionmentioning

confidence: 57%

The Placental NLRP3 Inflammasome and Its Downstream Targets, Caspase-1 and Interleukin-6, Are Increased in Human Fetal Growth Restriction: Implications for Aberrant Inflammation-Induced Trophoblast Dysfunction

Alfian

Chakraborty

Yong

et al. 2022

Cells

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Fetal growth restriction (FGR) is commonly associated with placental insufficiency and inflammation. Nonetheless, the role played by inflammasomes in the pathogenesis of FGR is poorly understood. We hypothesised that placental inflammasomes are differentially expressed and contribute to the aberrant trophoblast function. Inflammasome gene expression profiles were characterised by real-time PCR on human placental tissues collected from third trimester FGR and gestation-matched control pregnancies (n = 25/group). The functional significance of a candidate inflammasome was then investigated using lipopolysaccharide (LPS)-induced models of inflammation in human trophoblast organoids, BeWo cells in vitro, and a murine model of FGR in vivo. Placental mRNA expression of NLRP3, caspases 1, 3, and 8, and interleukin 6 increased (>2-fold), while that of the anti-inflammatory cytokine, IL-10, decreased (<2-fold) in FGR compared with control pregnancies. LPS treatment increased NLRP3 and caspase-1 expression (>2-fold) in trophoblast organoids and BeWo cell cultures in vitro, and in the spongiotrophoblast and labyrinth in the murine model of FGR. However, the LPS-induced rise in NLRP3 was attenuated by its siRNA-induced down-regulation in BeWo cell cultures, which correlated with reduced activity of the apoptotic markers, caspase-3 and 8, compared to the control siRNA-treated cells. Our findings support the role of the NLRP3 inflammasome in the inflammation-induced aberrant trophoblast function, which may contribute to FGR.

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“…Moreover, NLRP3 is expressed by myometrial tissues from women at term pregnancy (119). Together with the fact that inflammatory caspases (caspase-1 and caspase-4) have been detected in the human placenta (111-114, 120, 121), chorioamniotic membranes (111,117,118,122,123), and myometrium (122), this evidence indicates that gestational tissues possess the machinery to initiate inflammasome-mediated immune responses during pregnancy. Fig.…”

Section: Inflammasomes During Normal Pregnancymentioning

confidence: 90%

“…In the first trimester, in vitro studies have shown that placental cells (e.g., trophoblasts) expressed NLRP1, NLRP3, and NLRC4 (107, 108), as well as NLRP2 (109). At term ($37 wk of gestation), placental tissues also expressed these sensor molecules (107,(110)(111)(112)(113)(114)(115). Mirroring the expression of the NLRs, the adaptor protein ASC (or PYCARD) is also expressed in the placenta throughout pregnancy (106-108, 114, 115).…”

Section: Inflammasomes During Normal Pregnancymentioning

confidence: 99%

Inflammasomes: Their Role in Normal and Complicated Pregnancies

Gomez‐Lopez

Motomura

Miller

et al. 2019

The Journal of Immunology

103

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Abbreviations used in this article: AIM2, absent in melanoma-2; ASC, apoptosisassociated speck-like protein containing a caspase recruitment domain; DAMP, damage-associated molecule pattern; GSDMD, gasdermin D; NAIP, NLR family apoptosis inhibitory protein; NLR, nucleotide-binding oligomerization domain leucine-rich repeat-containing protein; NLRC4, CARD domain-containing protein-4; NLRP, NLR and pyrin domain-containing protein; PAMP, pathogen-associated molecular pattern; T3SS, type 3 secretion system.

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Expression and Clinical Significance of NOD-Like Receptor Protein 3 (NLRP3) and Caspase-1 in Fetal Membrane and Placental Tissues of Patients with Premature Rupture of Membrane

Cited by 5 publications

References 12 publications

Transcriptomic analysis delineates preterm prelabor rupture of membranes from preterm labor in preterm fetal membranes

Transcriptomic analysis delineates preterm prelabor rupture of membranes from preterm labor in preterm fetal membranes

The Placental NLRP3 Inflammasome and Its Downstream Targets, Caspase-1 and Interleukin-6, Are Increased in Human Fetal Growth Restriction: Implications for Aberrant Inflammation-Induced Trophoblast Dysfunction

Inflammasomes: Their Role in Normal and Complicated Pregnancies

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