Expression of Estrogen Receptor α by Decidual Macrophages in Preeclampsia

Vishnyakova, Polina; Poltavets, Anastasiya; Nikitina, Maria; Midiber, Konstantin; Mikhaleva, Liudmila M.; Muminova, Muminova К.Т.; Potapova, Alena; Ходжаева, З.С.; Pyregov, Pyregov A.V.; Elchaninov, Andrey; Fatkhudinov, Timur; Сухих, Г. Т.

doi:10.3390/biomedicines9020191

Cited by 7 publications

(6 citation statements)

References 57 publications

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“…This, in turn, is believed to tip the balance of pro-and anti-inflammatory macrophages towards inflammation, thereby contributing to the pathogenesis of PE. 169 Dysfunction of the decidual macrophages predisposed to PE, preterm labor, and pregnancy loss.…”

Section: Macrophages In Deciduamentioning

confidence: 99%

“…Levels of estrogen receptor α in decidua were significantly decreased in EOPE, along with a reduction in anti‐inflammatory HGF and CD206. This, in turn, is believed to tip the balance of pro‐and anti‐inflammatory macrophages towards inflammation, thereby contributing to the pathogenesis of PE 169 . Dysfunction of the decidual macrophages predisposed to PE, preterm labor, and pregnancy loss.…”

Section: Other Players: the Role Of Macrophagesmentioning

confidence: 99%

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New immune horizons in therapeutics and diagnostic approaches to Preeclampsia

Mukherjee

Singh

Karmakar

et al. 2023

American J Rep Immunol

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Hypertensive disorders of pregnancy (HDP) are one of the commonest maladies, affecting 5%–10% of pregnancies worldwide. The American College of Obstetricians and Gynecologists (ACOG) identifies four categories of HDP, namely gestational hypertension (GH), Preeclampsia (PE), chronic hypertension (CH), and CH with superimposed PE. PE is a multisystem, heterogeneous disorder that encompasses 2%–8% of all pregnancy‐related complications, contributing to about 9% to 26% of maternal deaths in low‐income countries and 16% in high‐income countries. These translate to 50 000 maternal deaths and over 500 000 fetal deaths worldwide, therefore demanding high priority in understanding clinical presentation, screening, diagnostic criteria, and effective management. PE is accompanied by uteroplacental insufficiency leading to vascular and metabolic changes, vasoconstriction, and end‐organ ischemia. PE is diagnosed after 20 weeks of pregnancy in women who were previously normotensive or hypertensive. Besides shallow trophoblast invasion and inadequate remodeling of uterine arteries, dysregulation of the nonimmune system has been the focal point in PE. This results from aberrant immune system activation and imbalanced differentiation of T cells. Further, a failure of tolerance toward the semi‐allogenic fetus results due to altered distribution of Tregs such as CD4+FoxP3+ or CD4+CD25+CD127(low) FoxP3+ cells, thereby creating a cytotoxic environment by suboptimal production of immunosuppressive cytokines like IL‐10, IL‐4, and IL‐13. Also, intracellular production of complement protein C5a may result in decreased FoxP3+ regulatory T cells. With immune system dysfunction as a major driver in PE pathogenesis, it is logical that therapeutic targeting of components of the immune system with pharmacologic agents like anti‐inflammatory and immune‐modulating molecules are either being used or under clinical trial. Cholesterol synthesis inhibitors like Pravastatin may improve placental perfusion in PE, while Eculizumab (monoclonal antibody inhibiting C5) and small molecular inhibitor of C5a, Zilucoplan are under investigation. Monoclonal antibody against IL‐17(Secukinumab) has been proposed to alter the Th imbalance in PE. Autologous Treg therapy and immune checkpoint inhibitors like anti‐CTLA‐4 are emerging as new candidates in immune horizons for PE management in the future.

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Section: Macrophages In Deciduamentioning

confidence: 99%

Section: Other Players: the Role Of Macrophagesmentioning

confidence: 99%

New immune horizons in therapeutics and diagnostic approaches to Preeclampsia

Mukherjee

Singh

Karmakar

et al. 2023

American J Rep Immunol

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“…In late pregnancy, the elevated macrophage and loss of trophoblast were observed under some abnormal pregnancy conditions, including early pregnancy loss, preeclampsia, FGR and gestational trophoblastic disease, indicating macrophages homeostasis is essential for maintaining decidual homeostasis in human pregnancy [47][48][49].…”

Section: Macrophagesmentioning

confidence: 99%

An Update Review of the Pathogenesis Hypothesis in Preeclampsia

Li¹,

Zhu²,

Xi³

2022

Clin. Exp. Obstet. Gynecol.

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Objectives: Hypertensive disorders occur in approximately 12% to 22% of pregnancies and cause substantial perinatal morbidity and mortality of both mother and fetus. Hypertensive disease is directly responsible for approximately 20% of maternal deaths and can be classified as chronic hypertension, gestational hypertension, preeclampsia-eclampsia, and chronic hypertension with superimposed preeclampsia. At present, the pathogenesis of preeclampsia is still unclear, we wrote this article to make a uptodate review of this disease. Mechanism: A comprehensive search of several databases was conducted from inception up to March 2022. The searched databases were Web of Science, MEDLINE,Ovid, and Cochrane Database of Systematic Reviews. The search strategy included the combinations of the following medical terms: Hypertensive disorders; preeclampsia; mechanism; pathogenesis hypothesis. Findings in Brief: At present,the pathogenesis of preeclampsia is still unclear, the theory of Genetic,Inflammatory Response, Immune Imbalance in Maternal-Fetal Interface, Oxidative Stress, Vascular Endothelial Cell Damage are supposed involved in the progress of preeclampsia. Conclusions: Although there are various theories mentioned above, none of the hypothesis can fully explain preeclampsia. More research is needed on the mechanism of preeclampsia.

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“…87 In addition, the lower expression of estrogen receptor a, hepatocyte growth factor, and CD206 has also been proved to lead to the imbalance of different inflammatory macrophages, thereby contributing to the pathogenesis of PE. 88 Finally, angiogenesis plays an important role not only in embryo implantation, but also in decidual angiogenesis in the early post-implantation period. The expression of COX2 is significantly decreased in the decidua of PE.…”

Section: Preeclampsia (Pe)mentioning

confidence: 99%

Decidualization and Related Pregnancy Complications

Tong

Yang

et al. 2021

Maternal-Fetal Medicine

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Decidualization is the differentiation of endometrial stromal cells into secretory decidual stromal cells. Human decidualization involves some amount of signaling molecules and pathways as well as genetic reprogramming, which is driven by the postovulatory rise in progesterone levels and local cyclic adenosine monophosphate production. Decidualization extends from the primary decidual zone to the secondary decidual zone, and then exits through apoptosis. Evidences support that decidual fibroblasts function as the pool of decidual stromal cells during pregnancy. Decidualization undergoes an acute inflammatory phase, an anti-inflammatory secretory phase to the final recession phase. The decidualization of the inner layer of endometrium, termed decidua, is the most critical determinant of pregnancy success, which can promote placenta formation, modulate immune tolerance, foster resistance to oxidative stress, sense embryo quality, and control labor. Failure to adequate decidualization in terms of hormones, biochemistry, and immunology leads to adverse pregnancy outcomes, including diseases such as preeclampsia, miscarriage, premature labor, repeated implantation failures, and some age-related decline in reproductive capacity. The development of animal models and in vitro culture systems combined with emerging technologies provides a powerful system to explore the mechanism of decidualization. However, decidualization is a dynamic, multi-step process, and translating of current research progress into disease predictions and interventions for pregnancy complications remains to be achieved. The study of periodic regeneration and spontaneous decidualization of the endometrium will be beneficial to the diagnosis and treatment of pregnancy diseases.

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Expression of Estrogen Receptor α by Decidual Macrophages in Preeclampsia

Cited by 7 publications

References 57 publications

New immune horizons in therapeutics and diagnostic approaches to Preeclampsia

New immune horizons in therapeutics and diagnostic approaches to Preeclampsia

An Update Review of the Pathogenesis Hypothesis in Preeclampsia

Decidualization and Related Pregnancy Complications

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