Maternal microbiome and the hypertensive disorder of pregnancy, preeclampsia

Beckers, Kalie F.; Sones, Jenny L.

doi:10.1152/ajpheart.00469.2019

Cited by 41 publications

(34 citation statements)

References 97 publications

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“…The levels of BP, urine protein and fetal death were increased, whereas fetal body weight was decreased in the L-NAME group in the present study. hypertension is one of the pathophysiological factors resulting in PE and injuries of the systematic inflammatory response (22). E2 improved the biochemical indexes and neonatal outcome by reducing BP, urine protein and the rate of stillbirths, increasing fetal weight and attenuating pathological injury, which indicated that the improvement of PE was associated with E2 treatment.…”

Section: Discussionmentioning

confidence: 95%

The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia

Lin¹,

Jin²,

Shan³

2020

Int J Mol Med

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Preeclampsia (PE), a hypertensive disorder during pregnancy, has adverse effects to both the mother and the fetus. Maternal inflammatory and vascular endothelial dysfunction are important factors in the pathogenesis of PE. The present study aimed to investigate the effects of estradiol (E2) on inflammatory and endothelial dysfunction in an N (omega)-nitro-L-arginine methyl ester (L-NAME)-induced rat model of PE. Adult pregnant female Sprague-dawley rats were divided into four equal groups between days 7 and 11 of gestation and treated as follows: i) Pregnant rats receiving daily intraperitoneal (i.p.) injections of equal volume of 0.9% normal saline (NS) (control group, n=12); ii) pregnant rats receiving daily i.p. injections of L-NAME at 50 mg/kg (L-NAME group, n=12); iii) pregnant rats receiving a daily i.p. injection of 50 mg/kg L-NAME and NS from day 11 (L-NAME + NS group, n=12); and iv) pregnant rats receiving daily i.p. injections of 50 mg/kg L-NAME and 100 µg/kg/day E2 from day 11 (L-NAME + E2 group, n=12). On day 21, blood pressure (BP) and the level of 24-h urine protein in the maternal rats, fetal weight and percentage of stillbirths following a cesarean section were recorded. The activities of nitric oxide (NO) and inducible NO synthase (iNOS), the levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, interferon-γ and monocyte chemoattractant protein-1], adherence factors (cd49d, intracellular adhesion molecule 1 and lymphocyte function-associated antigen-1) and uterine angiogenic status (Fms-like tyrosine kinase-1, vascular cell adhesion molecule and matrix metalloproteinase 2/9) were also assessed. In addition, the histopathology of the placenta, the expression of estrogen receptor α 36 (ERα36), ERα, ERβ and G protein-coupled ER, as well as the activation of the toll-like receptor 4 (TLR4) signaling pathway (TLR4, myeloid differentiation primary response 88, IL-1 receptor-associated kinase 4 and tumor necrosis factor receptor-associated factor 6) were evaluated by H&E staining, immunofluorescence and western blot assays. Treatment with L-NAME increased the BP, urine protein and rate of stillbirths and suppressed fetal weight compared with those in the control group. The L-NAME-induced effects were attenuated by the administration of E2. In addition, the administration of E2 decreased inflammation and NO levels and altered the uterine angiogenic status. The histological analysis of PE rat placenta in the E2-treated group confirmed the effects on biochemical parameters. Of note, E2 treatment significantly suppressed the TLR4 signaling pathway. In the rat model of PE, adverse outcomes including BP, fetal rat weight and proteinuria, high neonatal death rate, inflammatory response, oxidative stress and endothelial dysfunction were attenuated by exogenous E2 administration, which may present a novel approach for the clinical treatment of PE.

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Section: Discussionmentioning

confidence: 95%

The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia

Lin¹,

Jin²,

Shan³

2020

Int J Mol Med

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“…The cytotrophoblast fails to remodel spiral arteries, leading to hypoperfusion and ischemia of the placenta that provoke generalized maternal endothelial dysfunction and consequently the clinical manifestations of disease. Until now, placenta and fetus delivery has been the only effective treatment ( Martinez-Fierro et al, 2018a ; Beckers and Sones, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor Type 2 (FGF2) Administration Attenuated the Clinical Manifestations of Preeclampsia in a Murine Model Induced by L-NAME

et al. 2021

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Background: In preeclampsia, a hypertensive disorder of pregnancy, the poor remodeling of spiral arteries leads to placental hypoperfusion and ischemia, provoking generalized maternal endothelial dysfunction and, in severe cases, death. Endothelial and placental remodeling is important for correct pregnancy evolution and is mediated by cytokines and growth factors such as fibroblast growth factor type 2 (FGF2). In this study, we evaluated the effect of human recombinant FGF2 (rhFGF2) administration in a murine model of PE induced by NG-nitro-L-arginine methyl ester (L-NAME) to test if rhFGF2 administration can lessen the clinical manifestations of PE.Methods: Pregnant rats were administrated with 0.9% of NaCl (vehicle), L-NAME (60 mg/kg), FGF2 (666.6 ng/kg), L-NAME+FGF2 or L-NAME + hydralazine (10 mg/kg) from the 10th to 19th days of gestation. Blood pressure (BP), urine protein concentrations and anthropometric values both rat and fetuses were assessed. Histological evaluation of organs from rats delivered by cesarean section was carried out using hematoxylin and eosin staining.Results: A PE-like model was established, and it included phenotypes such as maternal hypertension, proteinuria, and fetal growth delay. Compared to the groups treated with L-NAME, the L-NAME + FGF2 group was similar to vehicle: the BP remained stable and the rats did not develop enhanced proteinuria. Both the fetuses and placentas from rats treated with L-NAME + FGF2 had similar values of weight and size compared with the vehicle.Conclusion: The intravenous administration of rhFGF2 showed beneficial and hypotensive effects, reducing the clinical manifestations of PE in the evaluated model.

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“…1,2 PE is a placental disorder leading to high maternal and fetal morbidity and mortality. 3,4 However, due to the lack of early prediction and targeted therapy, termination of pregnancy has become the most effective treatment. 5 Mechanistically, abnormal trophoblast function and uterine spiral artery remodeling disorders are recognized as the pathophysiological basis of PE.…”

Section: Introductionmentioning

confidence: 99%

Downregulated ribosomal protein L39 inhibits trophoblast cell migration and invasion by targeting E‐cadherin in the placenta of patients with preeclampsia

Jie

Sun

et al. 2021

The FASEB Journal

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Early-onset preeclampsia (PE) is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes. However, the mechanisms underlying the development of early-onset PE are not fully understood. Ribosomal protein L39 (RPL39) is a member of the S39E family of ribosomal proteins that plays an important role in stem cell self-renewal, cancer metastasis, and chemoresistance. In this study, we aimed to explore the potential function of RPL39 in placental trophoblast cells. We analyzed the expression of RPL39 in early-onset PE and normal placental tissues using real-time PCR, western blot analysis, and immunohistochemistry. The results showed that RPL39 was markedly downregulated in early-onset PE placental tissues. RPL39 knockdown inhibited trophoblast cell proliferation, migration, and invasion, as well as placental explant outgrowth. Flow cytometry analysis suggested that knockdown of RPL39 resulted in cell cycle arrest at the G0/G1 phase, but had no significant effect on cell apoptosis. We also found that RPL39 knockdown could alter cell morphology. We then measured the expression of the epithelial cell marker E-cadherin following knockdown of RPL39 in Bewo and HTR8/SVneo cells. RPL39 knockdown increased the expression of E-cadherin. Furthermore, E-cadherin expression was upregulated in placental explant outgrowth tissues transfected with RPL39 small interfering RNA. In conclusion, RPL39 plays an essential role in proliferation, invasion, and migration of trophoblast cells by targeting E-cadherin. Our findings provide novel insight into the mechanisms underlying the occurrence of early-onset PE.

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Maternal microbiome and the hypertensive disorder of pregnancy, preeclampsia

Cited by 41 publications

References 97 publications

The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia

The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia

Fibroblast Growth Factor Type 2 (FGF2) Administration Attenuated the Clinical Manifestations of Preeclampsia in a Murine Model Induced by L-NAME

Downregulated ribosomal protein L39 inhibits trophoblast cell migration and invasion by targeting E‐cadherin in the placenta of patients with preeclampsia

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