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Dysfunction of Liver Receptor Homolog-1 in Decidua: Possible Relevance to the Pathogenesis of Preeclampsia.

Zhang D, Cheng D, Liu T, Zhang Y, Chen ZJ, Zhang C - PLoS ONE (2015)

Bottom Line: However, the results of this study indicated that insufficient decidualization plays a significant role.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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.

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The expression of NR5A1 and NR5A2 after the induction of decidualization for 6 days.(A) The mRNA expression of PRL and IGFBP1 after induction of decidualization. (B) The mRNA expression of NR5A1 and NR5A2. (C) Bands representing NR5A1, NR5A2, and β-actin proteins on a western blot. (D) The relative expression levels of NR5A1 and NR5A2 to that of β-actin. The data were shown as mean ± SEM, n = 5, *P < 0.05, and **P < 0.01. Ctrl, control hESCs; db-cAMP+MPA, treated hESCs. PRL, prolactin; IGFBP1, insulin-like growth factor binding protein 1; *P < 0.05; **P < 0.01.
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pone.0145968.g004: The expression of NR5A1 and NR5A2 after the induction of decidualization for 6 days.(A) The mRNA expression of PRL and IGFBP1 after induction of decidualization. (B) The mRNA expression of NR5A1 and NR5A2. (C) Bands representing NR5A1, NR5A2, and β-actin proteins on a western blot. (D) The relative expression levels of NR5A1 and NR5A2 to that of β-actin. The data were shown as mean ± SEM, n = 5, *P < 0.05, and **P < 0.01. Ctrl, control hESCs; db-cAMP+MPA, treated hESCs. PRL, prolactin; IGFBP1, insulin-like growth factor binding protein 1; *P < 0.05; **P < 0.01.

Mentions: The detection of endometrial decidualization biomarkers (IGFBP1 and PRL) mRNA after treatment with db-cAMP and MPA indicated that the in vitro induced decidualization system was reliable (Fig 4A). During decidualization, the mRNA expression level of NR5A2 mRNA level increased by about 11-fold, while the transcription rate of NR5A1 was low and showed no statistically significant differences compared to that of the controls (Fig 4B). Similar results were demonstrated by western blot analysis (Fig 4C and 4D).


Dysfunction of Liver Receptor Homolog-1 in Decidua: Possible Relevance to the Pathogenesis of Preeclampsia.

Zhang D, Cheng D, Liu T, Zhang Y, Chen ZJ, Zhang C - PLoS ONE (2015)

The expression of NR5A1 and NR5A2 after the induction of decidualization for 6 days.(A) The mRNA expression of PRL and IGFBP1 after induction of decidualization. (B) The mRNA expression of NR5A1 and NR5A2. (C) Bands representing NR5A1, NR5A2, and β-actin proteins on a western blot. (D) The relative expression levels of NR5A1 and NR5A2 to that of β-actin. The data were shown as mean ± SEM, n = 5, *P < 0.05, and **P < 0.01. Ctrl, control hESCs; db-cAMP+MPA, treated hESCs. PRL, prolactin; IGFBP1, insulin-like growth factor binding protein 1; *P < 0.05; **P < 0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696807&req=5

pone.0145968.g004: The expression of NR5A1 and NR5A2 after the induction of decidualization for 6 days.(A) The mRNA expression of PRL and IGFBP1 after induction of decidualization. (B) The mRNA expression of NR5A1 and NR5A2. (C) Bands representing NR5A1, NR5A2, and β-actin proteins on a western blot. (D) The relative expression levels of NR5A1 and NR5A2 to that of β-actin. The data were shown as mean ± SEM, n = 5, *P < 0.05, and **P < 0.01. Ctrl, control hESCs; db-cAMP+MPA, treated hESCs. PRL, prolactin; IGFBP1, insulin-like growth factor binding protein 1; *P < 0.05; **P < 0.01.
Mentions: The detection of endometrial decidualization biomarkers (IGFBP1 and PRL) mRNA after treatment with db-cAMP and MPA indicated that the in vitro induced decidualization system was reliable (Fig 4A). During decidualization, the mRNA expression level of NR5A2 mRNA level increased by about 11-fold, while the transcription rate of NR5A1 was low and showed no statistically significant differences compared to that of the controls (Fig 4B). Similar results were demonstrated by western blot analysis (Fig 4C and 4D).

Bottom Line: However, the results of this study indicated that insufficient decidualization plays a significant role.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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.

Show MeSH
Related in: MedlinePlus