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.