Decidual and placental NOD1 is associated with inflammation in normal and preeclamptic pregnancies

Rakner, Johanne Johnsen; Silva, Gabriela Brettas; Mundal, Siv Boon; Thaning, Astrid Josefin; Elschot, Mattijs; Ostrop, Jenny; Thomsen, Liv Cecilie Vestrheim; Bjørge, Line; Gierman, Lobke; Iversen, Ann‐Charlotte

doi:10.1016/j.placenta.2021.01.014

Cited by 11 publications

(7 citation statements)

References 60 publications

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“…Moreover, a higher level of NOD1 protein is related to development of IUGR, which leads to fetal and neonatal morbidity [ 38 ]. On the other hand, there is a higher level of NOD1 in trophoblasts in normal pregnancy, which has direct effects on maternal–fetal communication [ 39 ]. Therefore, changes in expression of NOD1 may be associated with maternal–fetal communication, which may be beneficial for pregnancy establishment in sheep.…”

Section: Discussionmentioning

confidence: 99%

Early Pregnancy Modulates Expression of the Nod-like Receptor Family in Lymph Nodes of Ewes

Zhao

Cao

et al. 2022

Animals

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NOD receptors (NLRs) mediate adaptive immune responses and immune tolerance. Nevertheless, it is not clear if gestation modulates the NLR signaling pathway in lymph nodes of ewes. In this study, lymph nodes of ewes were collected at day 16 of the estrous cycle, and at days 13, 16 and 25 of gestation (n = 6 for each group). RT-qPCR, Western blot and immunohistochemistry analysis were used to analyze the expression of the NLR family, including NOD1, NOD2, CIITA, NAIP, NLRP1, NLRP3 and NLRP7. The data showed that early gestation enhanced expression of NOD1, CIITA, NLRP1, NLRP3 and NLRP7 mRNA, as well as proteins at day 16 of gestation, and the expression levels of NOD2, CIITA, NLRP1 and NLRP7 were higher at days 13 and 25 of gestation than day 16 of the estrous cycle. However, NOD1 expression was lower on days 13 and 25 of gestation compared to day 16 of the estrous cycle, and early gestation suppressed NAIP expression. In summary, early pregnancy modulated expression of the NLR family in ovine lymph nodes, which participates in immune regulation, and this modulation may be necessary for pregnancy establishment in ewes.

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Section: Discussionmentioning

confidence: 99%

Early Pregnancy Modulates Expression of the Nod-like Receptor Family in Lymph Nodes of Ewes

Zhao

Cao

et al. 2022

Animals

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“…PE is associated with increased decidual NOD1 expression. Activation of NOD1 is involved in the physiological in ammation that occurs during pregnancy through a cellular communication mechanism at the maternal-fetal interface and persists throughout pregnancy (Rakner et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of immune-related genes and immune cell infiltration in preeclampsia

Chen

Han

Zhang

et al. 2022

Preprint

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Preeclampsia (PE) is a complex multisystem disease, and its etiology remains unclear. The aim of this study was to identify potential immune-related diagnostic genes for PE, analyze the role of immune cell infiltration in PE. We used the dataset GSE25906 from Gene Expression Omnibus and immune-related genes from the ImmPort database. The differentially expressed genes (DEGs) were identified using the “limma” package, and the differentially expressed immune-related genes (DEIGs) were extracted from the DEGs and immune-related genes using Venn diagrams. The potential functions of DEIGs were determined. Furthermore, the protein–protein interaction network was obtained from the STRING database, and it was visualized using the Cytoscape software. Least absolute shrinkage and selection operator logistic regression and seven machine learning algorithms were used to verify the diagnostic markers of PE and build a predicting model. The model was validated using datasets GSE66273 and GSE75010. Finally, CIBERSORT was used to evaluate the infiltration of immune cells in PE tissues. Six genes (ACTG1, ENG, IFNGR1, ITGB2, NOD1, and SPP1) were identified. Datasets GSE66273 and GSE75010 were used to validate the model, and the area under the curve was 0.77 and 0.82, respectively. Immune cell infiltration analysis revealed an increase in plasma cells and gamma delta T cells and a decrease in resting natural killer cells in the high score group according to the predictive model risk values. We developed a risk model to predict PE and proved that immune imbalance at the maternal–fetal interface plays a key role in the pathogenesis of PE.

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“…A custom ImageJ script was used for the background correction and stitching of images [60][61][62]. The large tissue scans were further analyzed using custom MATLAB scripts (MathWorks, Natick, MA, USA, version 2017a) developed for the identification and automatic quantification of staining intensity [63][64][65], with the examiner blinded to the pregnancy outcome. Regions of the decidua with muscle cells, villous placental tissue, blood vessels, endometrial glands, and poor morphology were excluded by manually defining regions of disinterest (Figure 5A).…”

Section: Automated Quantification Of Protein Expressionmentioning

confidence: 99%

Divergent Regulation of Decidual Oxidative-Stress Response by NRF2 and KEAP1 in Preeclampsia with and without Fetal Growth Restriction

Mundal

Rakner

Silva

et al. 2022

IJMS

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Utero-placental development in pregnancy depends on direct maternal–fetal interaction in the uterine wall decidua. Abnormal uterine vascular remodeling preceding placental oxidative stress and placental dysfunction are associated with preeclampsia and fetal growth restriction (FGR). Oxidative stress is counteracted by antioxidants and oxidative repair mechanisms regulated by the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2). We aimed to determine the decidual regulation of the oxidative-stress response by NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) in normal pregnancies and preeclamptic pregnancies with and without FGR. Decidual tissue from 145 pregnancies at delivery was assessed for oxidative stress, non-enzymatic antioxidant capacity, cellular NRF2- and KEAP1-protein expression, and NRF2-regulated transcriptional activation. Preeclampsia combined with FGR was associated with an increased oxidative-stress level and NRF2-regulated gene expression in the decidua, while decidual NRF2- and KEAP1-protein expression was unaffected. Although preeclampsia with normal fetal growth also showed increased decidual oxidative stress, NRF2-regulated gene expression was reduced, and KEAP1-protein expression was increased in areas of high trophoblast density. The trophoblast-dependent KEAP1-protein expression in preeclampsia with normal fetal growth indicates control of decidual oxidative stress by maternal–fetal interaction and underscores the importance of discriminating between preeclampsia with and without FGR.

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Decidual and placental NOD1 is associated with inflammation in normal and preeclamptic pregnancies

Cited by 11 publications

References 60 publications

Early Pregnancy Modulates Expression of the Nod-like Receptor Family in Lymph Nodes of Ewes

Early Pregnancy Modulates Expression of the Nod-like Receptor Family in Lymph Nodes of Ewes

Identification and validation of immune-related genes and immune cell infiltration in preeclampsia

Divergent Regulation of Decidual Oxidative-Stress Response by NRF2 and KEAP1 in Preeclampsia with and without Fetal Growth Restriction

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