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Placental ischemia, resulting from inadequate remodeling of uterine spiral arteries, is a factor in the development of preeclampsia. However, the effect of endothelial progenitor cells that play a role in the vascular injury-repair program is largely unexplored during remodeling. Here, we observe that preeclampsia-afflicted uterine spiral arteries transition to a synthetic phenotype in vascular smooth muscle cells and characterize the regulatory axis in endothelial progenitor cells during remodeling in human decidua basalis. Excessive sEng, secreted by AMP-activated protein kinase (AMPK)-deficient endothelial progenitor cells through the inhibition of HO-1, damages residual endothelium and leads to the accumulation of extracellular matrix produced by vascular smooth muscle cells during remodeling, which is further confirmed by animal models. Collectively, our findings suggest that the impaired functionality of endothelial progenitor cells contributes to the narrowing of remodeled uterine spiral arteries, leading to reduced utero-placental perfusion. This mechanism holds promise in elucidating the pathogenesis of preeclampsia., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the expression of Krüppel-like factor 8 (KLF-8) and matrix metalloproteinase 9 (MMP-9) in placentas and their relationship with the pathogenesis of preeclampsia (PE)., Methods: Twenty-two women with PE(mild PE:4 cases; severe PE:18 cases) who received cesarean sections in the First Affiliated Hospital of Chongqing Medical University from September 2011 to March 2012 were recruited as the PE group (n = 22). And twenty women who received elective term cesarean section without perinatal complications were chosen as the control group (n = 20). Placentas were collected and immunohistochemical SP method were employed to detect the localization of KLF-8 protein.KLF-8 mRNA level was determined by quantitative real-time PCR technique and western blot analysis was used to quantify KLF-8 and MMP-9 protein levels., Results: (1) There was no difference of KLF-8 protein distribution in placentas of the PE group and the control group.It was mainly located in the nuclear and cytoplasm of syncytiotrophoblasts.KLF-8 immunostaining was apparently decreased in the placentas of preeclamptic women when compared with the control group.(2)The KLF-8 mRNA levels were significantly decreased in placentas of the PE group (0.69 ± 0.08) compared to those of the control group (1.14 ± 0.09, P < 0.01). (3) KLF-8 and MMP-9 protein levels significantly decreased in the PE placentas (0.68 ± 0.05 and 0.21 ± 0.03) when compared to the control group (0.94 ± 0.06 and 0.34 ± 0.03, respectively, P < 0.01).(4) There was a positive correlation between the expression of KLF-8 and MMP-9 protein in the placentas from PE and normal pregnancies (r = 0.64, P < 0.01)., Conclusions: KLF-8 mRNA and protein levels were decreased in placentas of PE patients compared to those of normotensive women.KLF-8 protein was primarily located in the invasion-related trophoblast cells and its expression had a positive correlation with MMP-9 levels.KLF-8 might have an important role in the pathogenesis of PE by regulation of trophoblast invasion.

Objective: To evaluate the expression of pentraxin 3 (PTX3) and tumor necrosis factor-alpha (TNF-α) in preeclampsia., Methods: Twenty-two preeclamptic patients, six preeclamptic patients with intrauterine growth restriction (IUGR) and 30 women with uncomplicated pregnancies were included in this study. The expression of PTX3 and TNF-α in placental tissue was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western immunoblotting. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of PTX3 and TNF-α in maternal sera. The localization and immunoreaction of PTX3 and TNF-α in placenta were determined via immunohistochemistry (IHC)., Results: Expression of PTX3 and TNF-α in placental tissues and maternal sera was significantly increased in preeclamptic patients, as well as in those with IUGR. PTX3 was mainly expressed in villous stroma, decidual cells and terminal villi, and TNF-α was mostly localized in trophoblast, vascular endothelial cells, decidual cells and in the stroma of the stem villi. Moreover, PTX3 expression was correlated with TNF-α expression in maternal sera of preeclamptic women., Conclusions: PTX3 and TNF-α are increased in preeclampsia and are likely involved in the pathogenesis of preeclampsia.

Objective: To explore the expression of pentraxin-3 (PTX3) in placentas from patients with severe preeclampsia and the relationship between PTX3 and the pathogenesis of severe preeclampsia., Methods: Fifty-three pregnant women who delivered from October 2010 to March 2011 in the First Affiliated Hospital of Chongqing Medical University were included in the study. Twenty-three women with severe preeclampsia were chosen as the preeclampsia group, and thirty healthy pregnant women were identified as the control group. All the women received cesarean section. The location of PTX3 protein in placentas was studied by immunohistochemical SP method. Quantitative real-time PCR technique and western blot analysis were employed to assay the levels of PTX3 mRNA and protein in placentas, respectively., Results: (1) The location of PTX3 protein in placentas: PTX3 protein was expressed in placentas from both groups, and there was no difference of PTX3 distribution between normal and preeclamptic placentas. PTX3 was mainly located in perivascular stroma, decidual cells and terminal villi. Neutrophilic infiltration was observed in the preeclamptic placentas. (2) The expression of PTX3 mRNA and protein in placentas:the level of PTX3 mRNA in placentas from the preeclampsia group was higher than that in the control group (1.98 ± 0.54 vs. 0.87 ± 0.27, P < 0.05). Compared with the control group, the level of PTX3 protein was significantly elevated in the preeclampsia group (1.42 ± 0.29 vs. 0.56 ± 0.25, P < 0.01)., Conclusion: The high expression of PTX3 in placentas from the preeclamptic patients suggests that PTX3 may be involved in the pathologic process of preeclampsia.

Objective: To study expression and activation of p38 mitogen activated protein kinase (MAPK) in vascular endothelial cells dysfunction in preeclampsia., Methods: From Sept. 2009 to Mar. 2010, 54 pregnant women underwent deliveries in the First Affiliated Hospital of Chongqing Medical University were enrolled in this study, including 20 patients in mild preeclampsia group, 16 patients in severe preeclampsia group and 18 women with term cesarean section without perinatal complications as control group. Placental endothelial cells were labeled by CD₃₄ to assay microvessel density (MVD) of each group. Immunohistochemical SP and western blot were used to detect localization and expression of p-p38 MAPK protein, respectively. The levels of sera soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured by ELISA., Results: (1) The MVD of placenta were 103 ± 3 in control group, 81 ± 5 in mild preeclampsia group and 63 ± 4 in severe group, respectively, which showed statistical difference among each group (P < 0.05). (2) The expression of p38 MAPK protein were 0.84 ± 0.05 in control group, 0.90 ± 0.14 in mild group and 0.86 ± 0.18 in severe group, which did not reach remarkable difference among each group (P > 0.05). The expression of p-p38 MAPK protein were 0.13 ± 0.05 in control group, 0.59 ± 0.12 in mild group and 1.16 ± 0.18 in severe group, which show statistical difference among each group (P < 0.05). (3) The localization of p-p38 was in trophoblast, endothelial cells and a few stromal cells in placenta. (4) The level of sFlt-1 and sEng: (1) The concentration of sFlt-1 and sEng were (5.2 ± 0.3) and (10.9 ± 0.4) µg/L in control group, (12.5 ± 1.2) and (20.4 ± 5.3) µg/L in mild group and (19.3 ± 3.0) and (29.5 ± 3.7) µg/L in severe group. When drawing paired comparison in those groups, the differences showed statistical difference (P < 0.05). (2) There were positive correlations between p-p38 MAPK protein levels and the concentrations of serum sFlt-1, sEng in preeclampsia groups (r = 0.68, P < 0.05; r = 0.87, P < 0.05)., Conclusions: The remarkable activation of the p38 MAPK in the placenta of patients with preeclampsia induced the increased levels of sFlt-l and sEng in maternal serum, which confer the injury of vascular endothelial cells that caused the significant decline of MVD in placentas. p38 MAPK signaling might be one of the key pathways in vascular endothelial cell dysfunction in preeclampsia.

Objective: To evaluate the expression and location of the growth arrest and DNA damage 45 alpha (Gadd45α) gene in human placenta and explore the relationship between Gadd45α and preeclampsia (PE)., Methods: Thirty-six women with preeclampsia who delivered from September 2009 to March 2010 in the First Affiliated Hospital of Chongqing Medical University were chosen as the study objects. They were classified into mild group (n = 20), severe group (n = 16) and elective term cesarean sections group without previous onset of labor and perinatal complications (control group, n = 18). Placentas were collected after they delivered and immunohistochemical streptravidin-biotin peroxidase (SP) method and histoscore were employed to detect the expression and localization of Gadd45α protein.Gadd45α mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR) technique and western blot analysis was used to quantify Gadd45α protein expression level., Results: (1) Gadd45α protein was detectable in placenta tissues of the mild and severe groups, mostly located in cytoplasm and nuclei of trophoblast, plus nuclei of vascular endothelial cells and a few stromal cells; whereas placenta tissues of control group showed weak staining, and only detectable in trophoblast, undetectable in vascular endothelial cells. (2) The Gadd45α mRNA levels in placenta tissues of the severe and mild groups were 0.75 ± 0.07 and 0.44 ± 0.13, respectively, significantly higher than that in control group (0.18 ± 0.04, P < 0.05); compared with mild group, Gadd45α mRNA level was significantly higher in severe group (P < 0.05). (3) The Gadd45α protein levels in placenta tissues of the severe and mild groups was 1.34 ± 0.17 and 0.65 ± 0.15, respectively, compared with mild group, Gadd45α protein level was higher in severe group (P < 0.05); they were both significantly higher than that in control group (0.22 ± 0.11, P < 0.05)., Conclusions: Gadd45α mRNA and protein levels in placenta tissues of patients with preeclampsia are higher than that of normotensive women, and up-regulated with aggravation of preeclampsia; the Gadd45α protein is located in trophoblast cells, which are closely related to pathogenesis of preeclampsia. These results indicate that Gadd45α plays an important role in the pathogenesis and progression of preeclampsia.

Objective: To determine the expression of Aquaporin 8(AQP8) in the fetal membrane and placenta of idiopathic polyhydramnios., Methods: The amnion, chorion and placenta were collected from 12 term pregnancies with idiopathic polyhydramnios( polyhydramnios group) and 12 term pregnancies who were normal (control group). The expression of AQP8 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of AQP8 protein was detected by immunohistochemistry., Results: The expression of AQP8 mRNA in amnion, chorion and placenta of polyhydramnios group was (0.78 +/- 0.13), (0.58 +/- 0.10), and (0.86 +/- 0.15) respectively, and that of control group was (0. 39 0.07), (0.45 +/- 0.09), and (0.34 +/- 0.09) respectively. The expression of AQP8 protein in amnion, chorion and placenta of polyhydramnios group was (0.195 +/- 0.024), (0.170 +/- 0.028), and (0.193 +/- 0.024) respectively, and that of control group was (0.151 +/- 0.018), (0.156 +/- 0.024), and (0.152 +/- 0.023) respectively. In all 3 types of tissues the expression of AQP8 mRNA of polyhydramnios group was higher than that of control group (P < 0.05). In amnion and placenta the expression of AQP8 protein of polyhydramnios group was also increased compared to that of control group (P < 0.05), but in chorion the difference in AQP8 protein expression between the two groups was not significant (P > 0.05)., Conclusion: The expression of AQP8 mRNA and protein is significantly increased in the amnion and placenta of polyhydramnios, suggesting that AQP8 may play an important role in the regulation of amniotic fluid volume.