Aspirin modulates STOX1 expression and reverses STOX1-induced insufficient proliferation and migration of trophoblast cells

He, Yuanying; Chen, Li; Liu, Chunhong; Han, Ying; Liang, Chao; Xie, Qingji; Cheng, Zhongping

doi:10.1016/j.preghy.2019.12.011

Cited by 9 publications

(6 citation statements)

References 21 publications

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“…Translational research suggests that aspirin and SPMs may improve both EVT invasion (deep placentation, a primary prevention) and decrease inflammatory pathways associated with the development of the great obstetrical syndromes (a tertiary prevention) 59–61 . Supporting the hypothesis that SPMs improve EVT invasion, He et al showed that aspirin modulates the storkhead‐box protein and improved trophoblast migration in a cell line model 62 . Ulu et al demonstrated that G protein‐coupled receptor 18 (GPR‐18, a receptor for RvD) was present in EVT cells 60 .…”

Section: Potential Therapeutic Treatments For the Great Obstetrical S...mentioning

confidence: 99%

“…[59][60][61] Supporting the hypothesis that SPMs improve EVT invasion, He et al showed that aspirin modulates the storkhead-box protein and improved trophoblast migration in a cell line model. 62 Ulu et al demonstrated that G protein-coupled receptor 18 (GPR-18, a receptor for RvD) was present in EVT cells. 60 Similarly, MacDonald et al described that formyl peptide receptor 2 (FPR2, a lipoxin receptor) was expressed in the decidua, and that LXA4 was upregulated by the beta-subunit of human chorionic gonadotropin (β-HCG), a hormone that peaks in the first trimester during EVT invasion.…”

Section: Biological Rationale For Aspirin As Treatment For the Great ...mentioning

confidence: 99%

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The great obstetrical syndromes and the placenta

Hoffman

2023

BJOG

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Although historically pre‐eclampsia, preterm birth, abruption, fetal growth restriction and stillbirth have been viewed as clinically distinct entities, a growing body of literature has demonstrated that the placenta and its development is the root cause of many cases of these conditions. This has led to the term ‘the great obstetrical syndromes’ being coined to reflect this common origin. Although these conditions mostly manifest in the second half of pregnancy, a failure to complete deep placentation (the transition from histiotrophic placentation to haemochorial placenta at 10–18 weeks of gestation via a second wave of extravillous trophoblast invasion), is understood to be key to the pathogenesis of the great obstetrical syndromes. While the reasons that the placenta fails to achieve deep placentation remain active areas of investigation, maternal inflammation and thrombosis have been clearly implicated. From a clinical standpoint these mechanisms provide a biological explanation of how low‐dose aspirin, which affects the COX‐1 receptor (thrombosis) and the COX‐2 receptor (inflammation), prevents not just pre‐eclampsia but all the components of the great obstetrical syndromes if initiated early in pregnancy. The optimal dose of low‐dose aspirin that is maximally effective in pregnancy remains a question open for further research. Additionally, other candidate medications have been identified that may also prevent pre‐eclampsia, and further study of them may offer therapeutic options beyond low‐dose aspirin. Interestingly, three of the eight identified compounds (hydroxychloroquine, metformin and pravastatin) are known to decrease inflammation.

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Section: Potential Therapeutic Treatments For the Great Obstetrical S...mentioning

confidence: 99%

Section: Biological Rationale For Aspirin As Treatment For the Great ...mentioning

confidence: 99%

The great obstetrical syndromes and the placenta

Hoffman

2023

BJOG

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“…Aspirin has favorable effects through alterations in phosphoproteins, transcription factors, and microRNAs implicated in placental apoptosis and trophoblast migration [128][129][130][131]. Aspirin facilitates trophoblast invasion by regulating a family of microRNAs that inhibit trophoblast invasion [131].…”

Section: Mysterious Beneficial Effects Of Low-dose Aspirin-is Cyclooxygenase Involved?mentioning

confidence: 99%

“…Thus, aspirin may augment extracellular trophoblast remodeling of the spiral arteries, which is deficient in preeclampsia. COX-2 is elevated in the process of apoptosis [129], so aspirin may decrease placental apoptosis by inhibiting COX-2.…”

Section: Mysterious Beneficial Effects Of Low-dose Aspirin-is Cyclooxygenase Involved?mentioning

confidence: 99%

The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta

Walsh

Strauss

2021

IJMS

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The road to low-dose aspirin therapy for the prevention of preeclampsia began in the 1980s with the discovery that there was increased thromboxane and decreased prostacyclin production in placentas of preeclamptic women. At the time, low-dose aspirin therapy was being used to prevent recurrent myocardial infarction and other thrombotic events based on its ability to selectively inhibit thromboxane synthesis without affecting prostacyclin synthesis. With the discovery that thromboxane was increased in preeclamptic women, it was reasonable to evaluate whether low-dose aspirin would be effective for preeclampsia prevention. The first clinical trials were very promising, but then two large multi-center trials dampened enthusiasm until meta-analysis studies showed aspirin was effective, but with caveats. Low-dose aspirin was most effective when started <16 weeks of gestation and at doses >100 mg/day. It was effective in reducing preterm preeclampsia, but not term preeclampsia, and patient compliance and patient weight were important variables. Despite the effectiveness of low-dose aspirin therapy in correcting the placental imbalance between thromboxane and prostacyclin and reducing oxidative stress, some aspirin-treated women still develop preeclampsia. Alterations in placental sphingolipids and hydroxyeicosatetraenoic acids not affected by aspirin, but with biologic actions that could cause preeclampsia, may explain treatment failures. Consideration should be given to aspirin’s effect on neutrophils and pregnancy-specific expression of protease-activated receptor 1, as well as additional mechanisms of action to prevent preeclampsia.

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“…Storkhead Box 1 (STOX1) is a transcription factor that is structurally and functionally similar to the forkhead box family and has shown to be involved in regulating proliferation and migration in a choriocarcinoma cell culture model for trophoblasts (He et al, 2020). Polymorphisms in STOX1 have been reported as a risk factor for early-onset PE in studies of Dutch and Turkish populations; however, this association was not confirmed in a separate Dutch study, in studies of Finnish or Korean populations, nor in mothers with European-ancestry (van Dijk et al, 2005;Berends et al, 2007;Iglesias-Platas et al, 2007;Kivinen et al, 2007;Kim et al, 2009;Pinarbasi et al, 2020).…”

Section: Storkhead Box 1 Overexpressionmentioning

confidence: 99%

Current State of Preeclampsia Mouse Models: Approaches, Relevance, and Standardization

2021

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Preeclampsia (PE) is a multisystemic, pregnancy-specific disorder and a leading cause of maternal and fetal death. PE is also associated with an increased risk for chronic morbidities later in life for mother and offspring. Abnormal placentation or placental function has been well-established as central to the genesis of PE; yet much remains to be determined about the factors involved in the development of this condition. Despite decades of investigation and many clinical trials, the only definitive treatment is parturition. To better understand the condition and identify potential targets preclinically, many approaches to simulate PE in mice have been developed and include mixed mouse strain crosses, genetic overexpression and knockout, exogenous agent administration, surgical manipulation, systemic adenoviral infection, and trophoblast-specific gene transfer. These models have been useful to investigate how biological perturbations identified in human PE are involved in the generation of PE-like symptoms and have improved the understanding of the molecular mechanisms underpinning the human condition. However, these approaches were characterized by a wide variety of physiological endpoints, which can make it difficult to compare effects across models and many of these approaches have aspects that lack physiological relevance to this human disorder and may interfere with therapeutic development. This report provides a comprehensive review of mouse models that exhibit PE-like symptoms and a proposed standardization of physiological characteristics for analysis in murine models of PE.

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Aspirin modulates STOX1 expression and reverses STOX1-induced insufficient proliferation and migration of trophoblast cells

Cited by 9 publications

References 21 publications

The great obstetrical syndromes and the placenta

The great obstetrical syndromes and the placenta

The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta

Current State of Preeclampsia Mouse Models: Approaches, Relevance, and Standardization

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