Suppressed Immune-Related Profile Rescues Abortion-Prone Fetuses: A Novel Insight Into the CBA/J × DBA/2J Mouse Model

Yi, Xiao-chun; Zhang, Jie; Liu, Huixiang; Yi, Tianxia; Ou, Yuhua; Liu, Meilan; Zhu, Liqiong; Chen, Hui; Zhang, Jianping

doi:10.1177/1933719119828042

Cited by 6 publications

(3 citation statements)

References 46 publications

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“…The mating combination CBA/J×DBA/2 has been widely used to mimic RSA due to the characteristic high fetal resorption rate and normal karyotype [61], providing a useful system to investigate immune system-related mechanisms that lead to the rejection of the semiallogeneic embryo and to explore methods that prevent pregnancy failure [62]. Many studies have suggested that fetal absorption in this model is due to an imbalance in Th1/Th2 cells, which can amplify inflammation and result in fetal rejection [63,64], while adoptive transfer of regulatory T cells (Tregs) can reestablish maternal immune tolerance and significantly reduce fetal resorption rates [65][66][67].…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle-Mediated Secretion of HLA-E by Trophoblasts Maintains Pregnancy by Regulating the Metabolism of Decidual NK Cells

Jiang¹,

Fei²,

Jin³

et al. 2021

Int. J. Biol. Sci.

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Extracellular vesicles derived from trophoblasts (T-EVs) play an important role in pregnancy, but the mechanism is not entirely clear. In this study, we found that HLA-E, which is mostly confined to the cytoplasm of trophoblast cells, was secreted by T-EVs. The level of HLA-E in T-EVs from unexplained recurrent spontaneous abortion (URSA) patients was lower than that in normal pregnancy (NP) and RSA patients who had an abnormal embryo karyotype (AK-RSA). T-EVs promoted secretion of IFN-γ and VEGFα by decidual NK (dNK) cells from URSA patients via HLA-E, VEGFα was necessary for angiogenesis and trophoblast growth, and IFN-γ inhibited Th17 induction. Glycolysis and oxidative phosphorylation (OxPhos) were involved in this process. Glycolysis but not OxPhos of dNK cells facilitated by T-EVs was dependent on mTORC1 activation. Inhibition of T-EV production in vivo increased the susceptibility of mice to embryo absorption, which was reversed by transferring exogenous T-EVs. T-EVs promoted secretion of IFN-γ and VEGFα by dNK cells to maintain pregnancy via Qa-1 in abortion-prone mouse models. This study reveals a new mechanism of pregnancy maintenance mediated by HLA-E via T-EVs.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicle-Mediated Secretion of HLA-E by Trophoblasts Maintains Pregnancy by Regulating the Metabolism of Decidual NK Cells

Jiang¹,

Fei²,

Jin³

et al. 2021

Int. J. Biol. Sci.

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“…After intraperitoneal exposure to PS-MPs, Hu et al observed a reduction in uterine blood supply and the proportion of decidual natural killer (dNK) cells while an increase of placental T helper cells, a polarization of M2 macrophage, and an immune suppressive state of cytokines ( Hu et al, 2021 ). Due to the intricacy of gestation, this result may not entirely align with our general conception ( Yi et al, 2019 ). Therefore, further research is necessary to uncover the mechanism underlying the MPs/NPs induced embryonic loss.…”

Section: Cross-generational Toxicity Of Mps/npsmentioning

confidence: 70%

Toxicity of microplastics and nanoplastics: invisible killers of female fertility and offspring health

Geng,

Liu,

et al. 2023

Front. Physiol.

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Microplastics (MPs) and nanoplastics (NPs) are emergent pollutants, which have sparked widespread concern. They can infiltrate the body via ingestion, inhalation, and cutaneous contact. As such, there is a general worry that MPs/NPs may have an impact on human health in addition to the environmental issues they engender. The threat of MPs/NPs to the liver, gastrointestinal system, and inflammatory levels have been thoroughly documented in the previous research. With the detection of MPs/NPs in fetal compartment and the prevalence of infertility, an increasing number of studies have put an emphasis on their reproductive toxicity in female. Moreover, MPs/NPs have the potential to interact with other contaminants, thus enhancing or diminishing the combined toxicity. This review summarizes the deleterious effects of MPs/NPs and co-exposure with other pollutants on female throughout the reproduction period of various species, spanning from reproductive failure to cross-generational developmental disorders in progenies. Although these impacts may not be directly extrapolated to humans, they do provide a framework for evaluating the potential mechanisms underlying the reproductive toxicity of MPs/NPs.

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“…The fetuses were small and dark, accompanied by necrosis and hemorrhage as absorbed fetuses. The absorption rate of fetuses was calculated as the number of absorbed fetuses/number of total fetuses × 100% ( 24 , 25 ).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation

et al. 2021

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Recurrent spontaneous abortion (RSA) is a common complication of pregnancy that affects the physical and mental health of pregnant women, and approximately 50% of the mechanisms are unclear. Our previous studies have found that high mobility group box 1 (HMGB1) molecules are highly expressed at the maternal-fetal interface of unexplained recurrent spontaneous abortion (URSA) patients. The purpose of this study was to further detect the expression of HMGB1 and pyroptosis in decidual tissue of URSA patients, and explore the potential mechanism of the protective role of HMGB1 in URSA patients and mouse model. The decidua tissues of 75 URSA patients and 75 women who actively terminated pregnancy were collected, and URSA mouse models were established and treated with HMGB1 inhibitor-aspirin. The expression of HMGB1, and their receptors (RAGE, TLR2, TLR4), pyroptosis-associated proteins (NLRP-3, caspase-1, GSDMD) and NF-κB was examined at the maternal-fetal interface of human and mouse. Our study found that HMGB1, NLRP-3, Caspase-1, GSDMD, RAGE, TLR2 and TLR4 were highly expressed and NF-κB signaling pathway were activated in the decidua tissue of URSA group. Moreover, immune cell disorder and co-localization of HMGB1 and macrophages were found at the maternal-fetal interface of URSA mice. However, HMGB1, TLR2, TLR4, NF-κB, and pyroptosis-associated proteins can be down-regulated by administering low-dose aspirin. These data may indicate that highly expressed HMGB1 was actively secreted by macrophages and then activated pyroptosis through the TLR2/TLR4-NF-κB pathway to cause aseptic inflammation, leading to the occurrence and development of URSA. Moreover, low-dose aspirin can reduce HMGB1 protein levels of serum and decidual in URSA.

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Suppressed Immune-Related Profile Rescues Abortion-Prone Fetuses: A Novel Insight Into the CBA/J × DBA/2J Mouse Model

Cited by 6 publications

References 46 publications

Extracellular Vesicle-Mediated Secretion of HLA-E by Trophoblasts Maintains Pregnancy by Regulating the Metabolism of Decidual NK Cells

Extracellular Vesicle-Mediated Secretion of HLA-E by Trophoblasts Maintains Pregnancy by Regulating the Metabolism of Decidual NK Cells

Toxicity of microplastics and nanoplastics: invisible killers of female fertility and offspring health

Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation

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