Downregulation of decidual SP1 and P300 is associated with severe preeclampsia

Abstract

Preeclampsia (PE) is a pregnancy-induced disorder characterized by hypertension and proteinuria after 20 weeks of gestation, affecting 5-7% of pregnancies worldwide. So far, the etiology of PE remains poorly understood. Abnormal decidualization is thought to contribute to the development of PE. SP1 belongs to the Sp/KLF superfamily and can recruit P300 to regulate the transcription of several genes. SP1 is also very important for decidualization as it enhances the expression of tissue factor. In this study, we investigated the expression of SP1 and P300 in deciduae and their relationship with PE. A total of 42 decidua samples were collected, of which 21 were from normal pregnant (NP) and 21 from severe PE. SP1 and P300 expression in deciduae and the levels of SP1 and P300 in cultured human endometrial stromal cells (hESCs) and primary hESCs during decidualization were determined. To further investigate the role of SP1 and P300 in human decidualization, RNA interference was used to silence SP1 and P300 in hESCs and primary hESCs. The following results were obtained. We found that the expressions of SP1 and P300 were reduced in decidual tissues with PE compared to those from NP. In the model of induction of decidualization, we found an increase in both and levels. Silencing of and resulted in abnormal decidualization and a significant reduction of decidualization markers such as insulin-like growth factor-binding protein1 and prolactin. Furthermore, the expression of vascular endothelial growth factor was also decreased upon and silencing. Similar results were observed in primary hESCs. Our results suggest that SP1 and P300 play an important role during decidualization. Dysfunction of SP1 and P300 leads to impaired decidualization and might contribute to PE.

Dysregulated GLUT1 May Be Involved in the Pathogenesis of Preeclampsia by Impairing Decidualization

“…Defective decidualization would cause adverse obstetric outcomes including PE. Our recent studies highlight the causative role of the abnormal decidualization in the progression of PE [11][12][13], and this view has been con rmed by other researches [14,15]. Nevertheless, our understanding of the association between abnormal decidualization and PE is just emerging.…”

Dysfunction of Decidual Macrophages Is a Potential Risk Factor in the Occurrence of Preeclampsia

“…Since no one can obtain a pregnant woman's decidua during her pregnancy, the samples analyzed were collected at the time of delivery. Although we cannot know the real state of the decidua in the first trimester of pregnancy when the placenta is formed, many studies have found that numerous decidualization-related genes are abnormally expressed in the decidua of PE patients (28,(61)(62)(63)(64)(65). Exploring the relationship between impaired decidualization and PE revealed that the maturity of the endometrium in the decidua and the natural killer cells of the uterus before the development of PE did not reach the ideal level (66).…”

Downregulation of decidual SKP2 is associated with human recurrent miscarriage

“…Proliferative endometrial tissues were obtained from women with normal menstrual cycles via endometrial biopsy at the time of diagnostic hysteroscopy. Primary ESCs were isolated according to previously described methods [ 26 ]. Briefly, endometrial tissues were fully washed with PBS and then minced in DMEM/F12.…”