Increased levels of serum IL-33 is associated with adverse maternal outcomes in placenta previa accreta

Özler, Sibel; Öztaş, Efser; Guler, Basak Gumus; Çağlar, Ali Turhan

doi:10.1080/14767058.2019.1679766

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…Although this study is focused on how IL-33 signaling contributes to pregnancy in mice, our findings may shed light on why abnormalities in IL-33 signaling are associated with a broad spectrum of pregnancy disorders and poor pregnancy outcomes in humans ( 4 , 5 , 7 – 17 , 68 , 69 ). Indeed, several key findings from our work parallel observations from studies on women with pregnancy disorders.…”

Section: Discussionmentioning

confidence: 99%

“…Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) in the IL33 gene that are associated with recurrent or idiopathic pregnancy loss ( 4 – 6 ). Other groups have reported abnormal levels of IL-33 or ST2 in serum or uterine tissue from women with preeclampsia ( 7 – 11 ), placenta previa accreta ( 12 ), gestational diabetes mellitus ( 13 ), and recurrent or impending pregnancy loss ( 14 , 15 ). Notably, both reduced and excessive IL-33 expression have been observed in distinct pregnancy disorders, suggesting that the magnitude and/or timing of IL-33 signaling may be a critical determinant of its specific biological effects on pregnancy outcomes ( 4 , 5 , 7 , 10 – 13 , 15 , 16 ).…”

mentioning

confidence: 99%

“…Other groups have reported abnormal levels of IL-33 or ST2 in serum or uterine tissue from women with preeclampsia ( 7 – 11 ), placenta previa accreta ( 12 ), gestational diabetes mellitus ( 13 ), and recurrent or impending pregnancy loss ( 14 , 15 ). Notably, both reduced and excessive IL-33 expression have been observed in distinct pregnancy disorders, suggesting that the magnitude and/or timing of IL-33 signaling may be a critical determinant of its specific biological effects on pregnancy outcomes ( 4 , 5 , 7 , 10 – 13 , 15 , 16 ). Nevertheless, few studies have addressed the functional requirement for IL-33 during pregnancy progression in vivo, and these have principally focused on very late gestation in lipopolysaccharide (LPS)-challenged mice ( 17 , 18 ).…”

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confidence: 99%

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Maternal IL-33 critically regulates tissue remodeling and type 2 immune responses in the uterus during early pregnancy in mice

Valero-Pacheco

Tang

Massri

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The pregnant uterus is an immunologically rich organ, with dynamic changes in the inflammatory milieu and immune cell function underlying key stages of pregnancy. Recent studies have implicated dysregulated expression of the interleukin-1 (IL-1) family cytokine, IL-33, and its receptor, ST2, in poor pregnancy outcomes in women, including recurrent pregnancy loss, preeclampsia, and preterm labor. How IL-33 supports pregnancy progression in vivo is not well understood. Here, we demonstrate that maternal IL-33 signaling critically regulates uterine tissue remodeling and immune cell function during early pregnancy in mice. IL-33–deficient dams exhibit defects in implantation chamber formation and decidualization, and abnormal vascular remodeling during early pregnancy. These defects coincide with delays in early embryogenesis, increased resorptions, and impaired fetal and placental growth by late pregnancy. At a cellular level, myometrial fibroblasts, and decidual endothelial and stromal cells, are the main IL-33 + cell types in the uterus during decidualization and early placentation, whereas ST2 is expressed by uterine immune populations associated with type 2 immune responses, including ILC2s, Tregs, CD4 + T cells, M2- and cDC2-like myeloid cells, and mast cells. Early pregnancy defects in IL-33–deficient dams are associated with impaired type 2 cytokine responses by uterine lymphocytes and fewer Arginase-1 + macrophages in the uterine microenvironment. Collectively, our data highlight a regulatory network, involving crosstalk between IL-33–producing nonimmune cells and ST2 + immune cells at the maternal–fetal interface, that critically supports pregnancy progression in mice. This work has the potential to advance our understanding of how IL-33 signaling may support optimal pregnancy outcomes in women.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Maternal IL-33 critically regulates tissue remodeling and type 2 immune responses in the uterus during early pregnancy in mice

Valero-Pacheco

Tang

Massri

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Gal-3 contributes to placentation by promoting trophoblastic proliferation and inhibiting its apoptosis [17] and enhancing the adhesion of trophoblastic cells to maternal decidua [18] . In PAS, decidual defects create a hypoxic environment that encourages further trophoblastic production of Gal-3 [19] , which subsequently enhances further trophoblastic invasion [18] .Additionally, the associated exaggerated inflammatory state, particularly the overproduction of interleukin (IL)-6 and IL-33, activates circulating macrophages, which in turn secrete Gal-3 [20,21] .…”

Section: Than Et Al (2015)mentioning

confidence: 99%

Galectin-3, a potential predictor and contributor of placenta accreta spectrum pathogenesis by inducing local vascular cell adhesion molecule-1 expression: A longitudinal study

Mohamed,

Abdel-Fadeil,

Ali

et al. 2023

BESPS

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Background: Galectin-3 (Gal-3) is a unique glycoprotein expressed in different tissues with several biological functions. Vascular cell adhesion molecule-1 (VCAM-1) is a cell adhesion molecule, expressed from vascular endothelium, and is implicated in the process of tissue angiogenesis. Both Gal-3 and VCAM-1 are expressed normally in placental tissue to achieve successful trophoblastic invasion. Placenta accreta spectrum (PAS) is a serious pregnancyrelated complication, with a progressively rising incidence worldwide. Massive trophoblastic invasion is a major contributor to its pathogenesis, and its diagnosis prenatally depends solely on Doppler ultrasonography. Aim: This study aimed to investigate the possible predictive value of serum Gal-3 in the occurrence of PAS and to highlight the potential involvement of Gal-3, macrophage recruitment, and VCAM-1 in its pathogenesis. Methods:This longitudinal study included 62 pregnant women; divided into group N, comprising31 pregnant women with normal placenta, and group P, comprising 31 pregnant women with PAS. Results: placental Gal-3 increased from 2.597 ± 0.061 to 4.392 ± 0.181 ng/mg protein, placental VCAM-1 increased from 2.901 ± 0.096 to 41.911 ± 1.885 ng/mg protein, and placental macrophage count increased from 2.323 ± 0.106 to 11.174 ± 0.643 /10 HPF. Serum Gal-3 had a significant predictive value for PA with a cutoff value ≥ 8.012 ng/ml. Conclusion:The overexpression of placental Gal-3 and VCAM-1 can be regarded as important key players in the pathogenesis of PAS. Remarkably, the detection of high serum levels of Gal-3 as early as the second trimester can predict the occurrence of PAS.

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“…IL-8 promotes migration and invasion of extravillous trophoblast cells during pregnancy, and its elevation in blood serum may serve as a biomarker for PAS [30]. The level of IL-33 is significantly higher in patients with PAS than in healthy pregnant women [31]. Despite the identified correlations between PAS and the levels of these circulating biomolecules in maternal blood, it is necessary to prove their specificity for PAS and their ability to distinguish it from other pregnancy complications.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during First-Trimester Screening

Timofeeva,

Fedorov,

Suhova

et al. 2024

IJMS

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Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial–myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, there is a high need for an additional non-invasive test to improve the diagnostic accuracy and to select the real PAS from the suspected ones in the first-trimester screening. miRNA signatures of placental tissue, myometrium, and blood plasma from women with PAS in the third trimester of pregnancy, as well as miRNA profiles in exosomes from the blood serum of women in the first trimester with physiologically progressing pregnancy, complicated by PAS or pre-eclampsia, were obtained using deep sequencing. Two logistic regression models were constructed, both featuring statistically significant parameters related to the levels of miR-26a-5p, miR-17-5p, and miR-101-3p, quantified by real-time PCR in native blood serum. These models demonstrated 100% sensitivity in detecting PAS during the first pregnancy screening. These miRNAs were identified as specific markers for PAS, showing significant differences in their blood serum levels during the first trimester in the PAS group compared to those in physiological pregnancies, early- or late-onset pre-eclampsia groups. Furthermore, these miRNAs exhibited differential expression in the PAS placenta and/or myometrium in the third trimester and, according to data from the literature, control angiogenesis. Significant correlations were found between extracellular hsa-miR-101-3p and nuchal translucency thickness, hsa-miR-17-5p and uterine artery pulsatility index, and hsa-miR-26a-5p and hsa-miR-17-5p with PLGF. The developed test system for early non-invasive PAS diagnosis based on the blood serum level of extracellular miR-26a-5p, miR-17-5p, and miR-101-3p can serve as an auxiliary method for first-trimester screening of pregnant women, subject to validation with independent test samples.

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Increased levels of serum IL-33 is associated with adverse maternal outcomes in placenta previa accreta

Cited by 7 publications

References 29 publications

Maternal IL-33 critically regulates tissue remodeling and type 2 immune responses in the uterus during early pregnancy in mice

Maternal IL-33 critically regulates tissue remodeling and type 2 immune responses in the uterus during early pregnancy in mice

Galectin-3, a potential predictor and contributor of placenta accreta spectrum pathogenesis by inducing local vascular cell adhesion molecule-1 expression: A longitudinal study

Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during First-Trimester Screening

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