Increased Toll-Like Receptor-Myeloid Differentiation Factor 88 Expression at the Maternal-Fetal Interface Is Associated with Spontaneous Abortion

He, Mengzhou; Zhou, Yuan; Jiang, Min; Li, Fanfan; Yang, Meitao; Fan, Yu; Deng, Dan

doi:10.1159/000468931

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…In this study, anti-β2-GP1 antibodies and ACAs were induced by injecting mice with β2-GP1 to construct the autoimmune RSA mouse model ( 17 ). Based on the current understanding of that disease model, aspirin, VitD3, and progesterone were used to intervene in the pregnancy outcome of autoimmune RSA.…”

Section: Introductionmentioning

confidence: 99%

Effects of aspirin, vitamin D3, and progesterone on pregnancy outcomes in an autoimmune recurrent spontaneous abortion model

Chen

Wei

et al. 2021

Braz J Med Biol Res

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High proportions of placental lymphocytes expressing DX5+/CD25+/FOXP3+/CD45+/CD4+ are beneficial to maintain immune tolerance and improve pregnancy outcomes. This study aimed to compare and evaluate the therapeutic effects of aspirin, vitamin D3 (VitD3), and progesterone on the autoimmune recurrent spontaneous abortion (RSA) model. The autoimmune RSA mouse model was constructed, and the embryo loss rate was calculated for each group. Then, primary mouse placental lymphocytes were isolated, and the expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ was detected through flow cytometry. The serum levels of anti-cardiolipin antibody (ACA), β2-GP1, CXCL6, IFN-γ, and IL-6 were measured by ELISA to evaluate the proportion of Th1 and Th2 cells. Autoimmune RSA significantly increased the embryo loss rate, which was improved by aspirin, VitD3, and progesterone treatment, and progesterone treatment had the best effect among the three treatments. The positive expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ in the VitD3 and progesterone groups was significantly higher than that in the autoimmune RSA group, and the expression was highest in the progesterone treatment group. In the plasma of autoimmune RSA mice, the ACA, β2-GP1, CXCL6, and IFN-γ levels were significantly higher and the IL-6 level was lower than the levels in control mice. All these changes could be reversed by aspirin and progesterone treatment. In conclusion, aspirin, VitD3 and progesterone treatment improved pregnancy outcomes in autoimmune RSA mice by regulating the Th1/Th2 balance and cytokines, and progesterone had the best effect of the three treatments.

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Section: Introductionmentioning

confidence: 99%

Effects of aspirin, vitamin D3, and progesterone on pregnancy outcomes in an autoimmune recurrent spontaneous abortion model

Chen

Wei

et al. 2021

Braz J Med Biol Res

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“…129 Specifically, it may shift the immune responses to the Th1 inflammatory responses and induce the death of trophoblast, which can result in miscarriage. 130 Furthermore, Inflammatory activation of endometrial immune cells by viruses can cause an excessive maternal immune response toward the trophoblastic invasion and induce miscarriage. 131 IL-1, IL-6, and tumor necrosis factor TNF-α are involved in the local inflammatory process and attract neutrophils to the site of infection.…”

Section: Alteration Of Trophoblast Invasion and Placental Dysfunctionmentioning

confidence: 99%

Potential role of viral infections in miscarriage and insights into the underlying molecular mechanisms

Heydarifard

Zadheidar

Yavarian

et al. 2022

Congenital Anomalies

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Intrauterine viruses can infect the decidua and placenta and cause adverse effects on the fetus during gestation. This review discusses the contribution of various viral infections to miscarriage and the molecular mechanisms by which viruses can cause devastating effects on healthy fetuses and induce miscarriage. Severe acute respiratory syndrome coronavirus 2 as newly emerged coronavirus was considered here, due to the concerns about its role during pregnancy and inducing miscarriage, as well.In this narrative review, an extensive literature search was conducted to find all studies investigating viral infections in miscarriage and their molecular mechanisms published over the past 20 years. The results of various studies investigating the roles of 20 viral infections in miscarriage are presented. Then, the mechanisms of pregnancy

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“…Recent studies have suggested that the placenta functions as an active immunologic barrier by trophoblasts recognizing and responding to microbes through innate immune pattern recognition receptors (PRRs) (6)(7)(8)(9). PRRs are essential for innate immune system responses to infectious microorganisms and recognize conserved sequences known as pathogen-associated molecular patterns (PAMPs).…”

Section: Introductionmentioning

confidence: 99%

NLRP3 mediates trophoblastic inflammasome activation and protects against Listeria monocytogenes infection during pregnancy

Gao¹,

Zhou²,

Zhang³

et al. 2022

Ann Transl Med

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Background: Intrauterine Listeria monocytogenes (L. monocytogenes) infections pose a major threat during pregnancy via affecting placental immune responses. However, the underlying mechanisms of placental defense against this pathogen remain ill-defined. Therefore, this study aims to investigate the function and the mechanism of inflammasomes on against L. monocytogenes infection during pregnancy.Methods: A listeriosis murine model and cell culture system was used to investigate the role of trophoblastic nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) in orchestrating innate immune responses to L. monocytogenes infection. Caspase-1 activity was determined using a caspase-1 activity colorimetric kit. NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) in placental tissue was detected by immunohistochemistry. NLRP3 in HTR-8/SVneo cells was also detected by immunofluorescence. The expression of interleukin 1β (IL-1β), NLRP3, ASC, and caspase-1 was detected by Western blot. We characterized the NLRP3 inflammasome in trophoblast cells according to whether L. monocytogenes infection increased the activation of caspase-1 and the release of IL-1β. For human or mouse IL-1β in the culture supernatants and mouse tissue lysates were analyzed using ELISA Kits.Results: Trophoblast cells constitutively expressed the components of the NLRP3 inflammasome. In vitro, L. monocytogenes triggers NLRP3 inflammasome activation in trophoblast cells by inducing caspase-1 activation, increasing the NLRP3 protein levels, IL-1β maturation and secretion in HTR-8/SVneo cells. In vivo, L. monocytogenes induces fetal resorption and IL-1β processing in pregnant mice. In addition, NLRP3-deficient mice were more prone to fetal loss than their wild-type counterparts following infection with L. monocytogenes at a lower infective dose. Conclusions:We conclude that trophoblast cells respond to L. monocytogenes infection through the NLRP3 receptor, resulting in inflammasome activation and IL-1β production, which prevents listeriosis during pregnancy.

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Increased Toll-Like Receptor-Myeloid Differentiation Factor 88 Expression at the Maternal-Fetal Interface Is Associated with Spontaneous Abortion

Cited by 5 publications

References 42 publications

Effects of aspirin, vitamin D3, and progesterone on pregnancy outcomes in an autoimmune recurrent spontaneous abortion model

Effects of aspirin, vitamin D3, and progesterone on pregnancy outcomes in an autoimmune recurrent spontaneous abortion model

Potential role of viral infections in miscarriage and insights into the underlying molecular mechanisms

NLRP3 mediates trophoblastic inflammasome activation and protects against Listeria monocytogenes infection during pregnancy

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