The pathologic changes of human placental macrophages in women with hyperglycemia in pregnancy

Ning, Jie; Zhang, Muqiu; Cui, Dong; Yang, Huixia

doi:10.1016/j.placenta.2022.11.004

Cited by 8 publications

(6 citation statements)

References 83 publications

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“…A comprehensive statistical analysis of the data from 44 placental extracts associated protein levels of MDMX, PICALM, OT-R and V1aR with labor at term and a number of clinical parameters and gestational complications. The predominant expression of MDMX on fetal macrophages (HC) [ 40 ] and the association of MDMX levels in the villi with most of the clinical characteristics we tested, suggest that MDMX has a central role in comorbidities, that originate from deficient trophoblast proliferation [ 46 ], and are linked to pre-existing conditions and environmental exposures [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

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Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Ho,

Chaput,

Sinkey

et al. 2024

Cell Commun Signal

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VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20–150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood–brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10–8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

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Section: Discussionmentioning

confidence: 99%

“…MDMX is predominantly expressed (Fig. 3C and D) on Hofbauer cells (HC) [36][37][38][39][40] that are targets of Zika and other viruses [41]. Strong MDMX staining was limited to the cytoplasm of HC, easily identified within the villous stroma, some within stromal channels (Fig.…”

Section: Immunohistochemistry and Whole Mount Immunofluorescencementioning

confidence: 99%

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Ho,

Chaput,

Sinkey

et al. 2024

Cell Commun Signal

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“…According to some authors, there is a strong possibility that in diabetes, HBCs may undergo an inter-subgroup conversion or potentially adopt a novel, distinct phenotype, rather than simply maintaining M2 polarisation or transitioning to the pro-inflammatory M1 phenotype ( 49 ). This hypothesis is also supported by the fact that the production of proinflammatory cytokines is not solely associated with the M1 phenotype.…”

Section: Discussionmentioning

confidence: 99%

The interplay of inflammation and placenta in maternal diabetes: insights into Hofbauer cell expression patterns

Tauber,

Burianova,

Koubova

et al. 2024

Front. Immunol.

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IntroductionInflammation of the placenta is harmful to both the fetus and the mother. Inflammation is strongly associated with diabetes, a common complication of pregnancy. Hofbauer cells (HBCs), unique immune system cells of fetal origin in the placenta, play complex roles, including growth of placental villi and their branching, stromal remodelling, and angiogenesis.MethodsOur study investigated the expression of IL-1β, IL-10, CYP2C8, CYP2C9, CYP2J2 and sEH in HBCs from patients with type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM) compared to healthy controls using immunohistochemistry. We also assessed the structure of the villus stroma using Masson´s trichrome.ResultsIn T1DM, HBCs showed inflammatory activation characterised by increased IL-1β and decreased CYP epoxygenase expression compared to normal placentas. Conversely, significant inflammation in HBCs appeared less likely in GDM, as levels of IL-1β and CYP epoxygenases remained stable compared to normal placentas. However, GDM showed a significant increase in sEH expression. Both types of diabetes showed delayed placental villous maturation and hypovascularisation, with GDM showing a more pronounced effect.ConclusionThe expression profiles of IL-1β, CYP epoxygenases and sEH significantlly differ between controls and diabetic placentas and between T1DM and GDM. These facts suggest an association of the CYP epoxygenase-EETs-sEH axis with IL-1β expression as well as villous stromal hypovascularisation. Given the stable high expression of IL-10 in both controls and both types of diabetes, it appears that immune tolerance is maintained in HBCs.

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“…9 Some studies have shown that mechanisms related to glucose metabolism are involved in the pathogenesis of hypertensive disorders in pregnancy; in addition, PE and HIP share many common risk factors and similarities in pathophysiology, including immune system disorder, vascular endothelial dysfunction, and insulin resistance. [10][11][12][13][14][15] In this study, we focused on pregnant women with HIP, with the hope of screening those at risk of preeclampsia through simple routine pregnancy care information so that we can take more effective interventions.…”

Section: Introductionmentioning

confidence: 99%

A Prediction Model of Preeclampsia in Hyperglycemia Pregnancy

Fang,

Liu,

et al. 2024

DMSO

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To investigate the risk factors associated with preeclampsia in hyperglycemic pregnancies and develop a predictive model based on routine pregnancy care. Patients and Methods:The retrospective collection of clinical data was performed on 951 pregnant women with hyperglycemia, including those diagnosed with diabetes in pregnancy (DIP) and gestational diabetes mellitus (GDM), who delivered after 34 weeks of gestation at the Maternal and Child Health Hospital Affiliated to Anhui Medical University between January 2017 and December 2019. Observation indicators included liver and kidney function factors testing at 24-29 +6 weeks gestation, maternal age, and basal blood pressure. The indicators were screened univariately, and the "rms" package in R language was applied to explore the factors associated with PE in HIP pregnancy by stepwise regression. Multivariable logistic regression analysis was used to develop the prediction model. Based on the above results, a nomogram was constructed to predict the risk of PE occurrence in pregnant women with HIP. Then, the model was evaluated from three aspects: discrimination, calibration, and clinical utility. The internal validation was performed using the bootstrap procedure. Results: Multivariate logistic regression analysis showed that cystatin C, uric acid, glutamyl aminotransferase, blood urea nitrogen, and basal systolic blood pressure as predictors of PE in pregnancy with HIP. The predictive model yielded an area under curve (AUC) value of 0.8031 (95% CI: 0.7383-0.8679), with an optimal threshold of 0.0805, at which point the sensitivity was 0.8307 and specificity of 0.6604. Hosmer-Lemeshow test values were P = 0.3736, Brier score value was 0.0461. After 1000 Bootstrap resamplings for internal validation, the AUC was 0.7886, the Brier score was 0.0478 and the predicted probability of the calibration curve was similar to the actual probability. A nomogram was constructed based on the above to visualize the model. Conclusion:This study developed a model for predicting PE in pregnant women with HIP, achieving high predictive performance of PE risk through the information of routine pregnancy care.

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The pathologic changes of human placental macrophages in women with hyperglycemia in pregnancy

Cited by 8 publications

References 83 publications

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

The interplay of inflammation and placenta in maternal diabetes: insights into Hofbauer cell expression patterns

A Prediction Model of Preeclampsia in Hyperglycemia Pregnancy

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