Decidual macrophages in recurrent spontaneous abortion

Zhao, Qiuyan; Li, Qinghui; Fu, Yaoyao; Ren, Chune; Jiang, Aifang; Meng, Yuguang

doi:10.3389/fimmu.2022.994888

Cited by 22 publications

(14 citation statements)

References 123 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been fully elucidated that decidual macrophages contribute the second largest decidual leukocyte population at the maternal-foetal interface in the first trimester, next to natural killer cells [ 4 ]. Emerging evidence has indicated an association between the disturbance of decidual macrophages and the occurrence of RSM [ 2 ]. Our current study sought to integrate DNA methylation data with transcriptome profiles to explore key epigenetic features in decidual macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…Recurrent spontaneous miscarriage (RSM) refers to two or more consecutive spontaneous abortions with the same spouse before the 20th week of gestation [ 1 ]. RSM accounts for approximately 2–5% of the total pregnancies [ 2 ]. Although concentrated research has identified numerous causes of RSM, such as chromosomal abnormalities, abnormal reproductive structure, endocrinopathies, and thrombophilic disorders, 50% of RSM cases are still unexplained [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Upregulation of GPR133 expression impaired the phagocytosis of macrophages in recurrent spontaneous miscarriage

Sun,

Yao,

et al. 2024

Epigenetics

View full text Add to dashboard Cite

Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from microorganisms or pathogens. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia and recurrent spontaneous miscarriage (RSM). However, the mechanisms by which decidual macrophages are involved in the occurrence of adverse pregnancy outcomes have not been elucidated. Here we integrated DNA methylation and gene expression data from decidua macrophages to identify potential risk factors related to RSM. GPR133 was significantly hypomethylated and upregulated in decidual macrophages from RSM patients. Further demethylation analysis demonstrated that GPR133 expression in decidual macrophages was significantly increased by 5-Aza-dC treatment. In addition, the influence of GPR133 on the phagocytic ability of macrophages was explored. Phagocytosis was impaired in the decidual macrophages of RSM patients with increased GPR133 expression. Increased GPR133 expression induced by demethylation treatment in the decidual macrophages of healthy control patients led to a significant decrease in phagocytic function. Importantly, knockdown of GPR133 resulted in a significant improvement in the phagocytic function of THP-1 macrophages. In conclusion, the existing studies have shown the influence of GPR133 on the phagocytic function of decidual macrophages and pregnancy outcomes, providing new data and ideas for future research on the role of decidual macrophages in RSM.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Upregulation of GPR133 expression impaired the phagocytosis of macrophages in recurrent spontaneous miscarriage

Sun,

Yao,

et al. 2024

Epigenetics

View full text Add to dashboard Cite

show abstract

“…DMφ, characterised by M2-like macrophages, are integral components of decidual immune cells at the maternal-fetal interface, crucial for maintaining maternal-fetal tolerance and trophoblast invasion [29]. The removal of macrophages in pregnant rats results in abortions, highlighting their signi cance in sustaining normal pregnancies [16,30].…”

Section: Discussionmentioning

confidence: 99%

The effect of Toxoplasma gondii infection on Galectin-9 expression in decidual macrophages contributing to dysfunction of decidual NK cells during pregnancy

Wang,

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Toxoplasma gondii infection causes adverse pregnancy outcomes by affecting the expression of immunotolerant molecules in decidual immune cells. Galectin-9 (Gal-9) is widely expressed in decidual macrophages (dMφ) and is crucial for maintaining normal pregnancy by interacting with the immunomodulatory protein Tim-3. However, the effects of T. gondii infection on Gal-9 expression levels in dMφ during pregnancy, as well as the impact of altered Gal-9 expression levels on the maternal-fetal tolerance function of dNK cells, are still unknown. Methods: Pregnancy outcomes of T. gondii infected C57BL/6 and Lgals9-/- pregnant mice models were recorded. The pathological change was evaluated by HE staining. The expression of Gal-9 in T. gondii infected dMφ were examined using flow cytometry and immunofluorescence. Expressions of Gal-9, JNK, p-JNK, FOXO1 were detected by Western Blot. The binding of FOXO1 to the promoter of Lgals9 was determined by ChIP-PCR. Supernatants from control or infected dMφ was co-cultured with purified human dNK cells with or without recombinant human Gal-9 protein (rhGal-9) or neutralized antibody of Tim-3, the expression of ERK, p-ERK, CREB, p-CREB, T-bet, IL-10 and IFN-γ were assayed by Western Blot. Results: T. gondii infection promoted JNK phosphorylation and increased FOXO1 expression in dMφ, resulting in reduction of Gal-9 due to the elevated binding of FOXO1 with Lgals9 promoter. Downregulation of Gal-9 enhanced the phosphorylation of ERK and inhibited phosphorylation of CREB and expression of IL-10, and promoted the expression of T-bet and IFN-γ. In mice model, knockout of Gal-9 aggravated adverse pregnancy outcomes caused by T. gondii infection during pregnancy. Conclusions: T. gondii infection suppressed Gal-9 expression in dMφ by activating the JNK/FOXO1 signaling pathway, and reduction of Gal-9 resulted in dysfunction of dNK via Gal-9/Tim-3 interaction. This study provided new insights for the molecular mechanisms of the adverse pregnancy outcomes caused by T. gondii.

show abstract

“…Thus, these results suggested that NCK1 may regulate PD-L1-mediated macrophage proliferation. Previous studies have reported that RM was closely associated with immune dysfunction, such as imbalance of macrophage polarization and dysfunction of macrophage cytokine secretion ( Zhao et al, 2022 ). Thus, enhanced proliferation of macrophages may be detrimental to pregnancy maintenance by causing immune dysfunction at the maternal-fetal interface.…”

Section: Discussionmentioning

confidence: 99%

Reduced NCK1 participates in unexplained recurrent miscarriage by regulating trophoblast functions and macrophage proliferation at maternal-fetal interface

Ding,

Zhang,

Bao

et al. 2023

Genet. Mol. Biol.

View full text Add to dashboard Cite

Recurrent miscarriage (RM) seriously affects the physical and mental health of women of childbearing age, and 50% of the causes are unknown. Thus, it is valuable to investigate the causes of unexplained recurrent miscarriage (uRM). Similarities between tumor development and embryo implantation make us realize that tumor studies are informative for uRM. The non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1) is highly expressed in some tumors, and can promote tumor growth, invasion and migration. In this present paper, we firstly explore the role of NCK1 in uRM. We find that the NCK1 and PD-L1 are greatly reduced in peripheral blood mononuclear cells (PBMC) and decidua from patients with uRM. Next, we construct NCK1-knockdown HTR-8/SVneo cells, and find that NCK1-knockdown HTR-8/SVneo cells exhibit reduced proliferation and migration ability. Then we demonstrate that the expression of PD-L1 protein is decreased when the NCK1 is knocked down. In co-culture experiments with THP-1 and differently treated HTR-8/SVneo cells, we observe significantly increased proliferation of THP-1 in NCK1-knockdown group. In conclusion, NCK1 may be involved in RM by regulating trophoblast proliferation, migration, and regulating PD-L1mediated macrophage proliferation at the maternal-fetal interface. Moreover, NCK1 has the potential to be a new predictor and therapeutic target.

show abstract

Decidual macrophages in recurrent spontaneous abortion

Cited by 22 publications

References 123 publications

Upregulation of GPR133 expression impaired the phagocytosis of macrophages in recurrent spontaneous miscarriage

Upregulation of GPR133 expression impaired the phagocytosis of macrophages in recurrent spontaneous miscarriage

The effect of Toxoplasma gondii infection on Galectin-9 expression in decidual macrophages contributing to dysfunction of decidual NK cells during pregnancy

Reduced NCK1 participates in unexplained recurrent miscarriage by regulating trophoblast functions and macrophage proliferation at maternal-fetal interface

Contact Info

Product

Resources

About