Abstract
Preeclampsia (PE) is a multisystem disorder unique to Homo sapiens that is known to cause maternal and perinatal mortality and morbidity. Between 5–7% of all pregnancies are affected by PE and it is responsible for approximately 50,000 maternal deaths annually. The pathogenesis of PE remains poorly understood. However, the results of this study indicated that insufficient decidualization plays a significant role. NR5A1 and NR5A2 are orphan members of the Ftz-F1 subfamily of nuclear receptors and are involved in mammal follicular development, female reproduction, steroidogenesis, and decidualization. The expression of NR5A1 and NR5A2 in the human decidua and their functions during decidualization were investigated using in vitro cultured cells by real-time PCR, immunohistochemistry, western blotting, and siRNA techniques. The results demonstrated that the levels of NR5A2 mRNA and protein in the decidual tissues of women with PE were lower than those of normal pregnant women. However, the levels of NR5A1 mRNA and protein did not significantly differ between groups. The expression of NR5A2 was upregulated after in vitro decidualization, but the expression of NR5A1 remained low and showed no difference compared with that of the control cells. Knocking down of NR5A2 in human endometrial stromal cells (hESC) resulted in a significant reduction in their expression of decidualization markers (IGFBP1 and PRL) and signaling pathway molecules (WNT4 and BMP2) (P < 0.05). From these data, we concluded that NR5A2 is pivotal for the decidualization of decidual tissues and cultured human endometrial stromal cells. Disorders of the endometrium in decidual tissues may be associated with the abnormal decidualization thought to cause PE.
Highlights
Preeclampsia (PE) is characterized by the occurrence of hypertension and/or proteinuria after 20 weeks of gestation
The present study represents a comprehensive investigation of NR5A1 and NR5A2 expression levels in PE pregnancies
Transcription and translation of NR5A2 were significantly lower in the decidual tissues of women with severe preeclampsia (SPE) compared to those of the women in the gestational matched control group, whereas no significant differences in NR5A1 expression were observed between the two groups
Summary
Preeclampsia (PE) is characterized by the occurrence of hypertension and/or proteinuria after 20 weeks of gestation. It is a serious complication of the second half of pregnancy, labor, or the early period after delivery. PE is responsible for maternal and fetal morbidity and mortality affecting 5–7% of all pregnancies [1] and is responsible for 42% of all maternal deaths and 15% of all preterm deliveries [2]. Fetal PE syndrome can manifest as preterm delivery, growth restriction, placental abruption, and fetal distress [3]. The long-term effects of PE can include cardiovascular complications for both the mother and the child
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