Analysis of expression levels of endoplasmic reticulum stress and trophoblast apoptosis-related markers in placental tissues of early and late-onset severe preeclampsia

Acta Universitatis Medicinalis Anhui 2025 01 v.60 102-108     font:big middle small

Found programs: National Natural Science Foundation of China (No. 81801477);Funding for the Training of Echelon Talents and Academic Leaders in The First Affiliated Hospital of Anhui Medical University (No. 1310)

Authors:Kang Fen; Wu Yongyuan; Li Xiaolan

Keywords:preeclampsia;placenta;endoplasmic reticulum stress;proliferation;apoptosis;gestation weeks

DOI:10.19405/j.cnki.issn1000-1492.2025.01.014

〔Abstract〕 Objective To explore the correlation between the expression levels of endoplasmic reticulum stress(ERS) and trophoblast apoptosis-related markers and severe preeclampsia(SPE) in placental tissues of pregnant women with early-and late-onset SPE and normal pregnancy. Methods Placental tissues from 20 early and late haired severe preeclamptic singleton pregnant women who attended the Hospital were collected(early-onset group, late-onset group), and 20 cases pregnant women of normal blood pressure and no other pregnancy complications who delivered in our hospital during the same period were selected as the normal group. Transmission electron microscopy was used to observe the ultrastructure of the endoplasmic reticulum of trophoblast cells in placental tissues. Protein blotting assay was used to detect the expression levels of endoplasmic reticulum stress-related proteins, including Glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), Phosphorylated eukaryotic translation initiation factor 2α(p-eIF2α) and Phosphatidylinositol-requiring enzyme 1(p-IRE1)α. Immunohistochemistry assay was used to detect the expression of proliferating cell nuclear antigen(Ki67), a proliferation marker, in placental tissues, and TUNEL staining was used to detect placental tissue trophoblast apoptosis. Results The endoplasmic reticulum of trophoblast cells in the placental tissues of the normal pregnant women group was normal in volume, with no dilatation or swelling. In contrast, the endoplasmic reticulum of placental tissues in the severe preeclampsia group showed obvious edema and significant dilatation, and the dilatation was more obvious in the early-onset group than in the late-onset group. The expression level of endoplasmic reticulum stress-related proteins GRP78(P<0.001,P<0.05) and CHOP(P<0.01,P<0.001), the phosphorylation levels of eIF2α(P<0.000 1,P<0.01) and IRE1α(P<0.000 1,P<0.001) increased in placental tissues of both early-onset and late-onset groups compared to those of the normal group. The p-eIF2α/eIF2α(P<0.001) to p-IRE1α/IRE1α ratio(P<0.05) and GRP78(P<0.01) protein expression levels were significantly higher in the early-onset group than in the late-onset group. Compared with the normal group, the number of Ki67-positive cells per field of view was significantly reduced in the early-onset and late-onset groups(P<0.000 1,P<0.05), and the number of Ki67-positive cells was significantly lower in the early-onset group than in the late-onset group(P<0.01). There were more positive apoptotic cells per field of view in the placental tissues of the early-onset group, and the apoptosis rate of trophoblast cells was significantly higher than that in the other two groups(P<0.001,P<0.01). Conclusion Increased trophoblast apoptosis and suppressed proliferation in placental tissues of patients with severe preeclampsia may be associated with endoplasmic reticulum stress overactivation, and the activation level is higher in placental tissues of early-onset severe preeclampsia than that of late-onset group.