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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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Molecular expression mechanism underlying the effect of NR5A2 interference.(A) Efficiency of NR5A2 siRNA mediated knockdown. (B) The mRNA expression of PRL and IGFBP1 after the knocking down of NR5A2. (C) The mRNA expression of WNT4 and BMP2 after the knocking down of NR5A2. (D) The mRNA expression of BMP2 and NR5A2 after the knocking down of BMP2. The data are expressed as the mean ± SEM. PRL, prolactin; IGFBP1, insulin-like growth factor binding protein 1; *P < 0.05; **P < 0.01; ***P < 0.001.
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pone.0145968.g005: Molecular expression mechanism underlying the effect of NR5A2 interference.(A) Efficiency of NR5A2 siRNA mediated knockdown. (B) The mRNA expression of PRL and IGFBP1 after the knocking down of NR5A2. (C) The mRNA expression of WNT4 and BMP2 after the knocking down of NR5A2. (D) The mRNA expression of BMP2 and NR5A2 after the knocking down of BMP2. The data are expressed as the mean ± SEM. PRL, prolactin; IGFBP1, insulin-like growth factor binding protein 1; *P < 0.05; **P < 0.01; ***P < 0.001.

Mentions: To further elucidate the function of NR5A2 during the in vitro decidualization of hESCs, the level of NR5A2 mRNA in the cells was knocked down using RNA interference to silence endogenous NR5A2 expression. The siRNA targeting NR5A2 mRNA or a non-targeting siRNA were transfected into hESCs for 24 h and then subjected to differentiation. Fig 5A showed that the hESCs transfected with NR5A2 siRNA exhibited a reduction of almost 90% in NR5A2 mRNA expression compared to that of the cells transfected with control siRNA. This down-regulation of NR5A2 expression in hESCs resulted in a significant reduction in the expression of mRNAs corresponding to PRL and IGFBP1 (Fig 5B).


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)

Molecular expression mechanism underlying the effect of NR5A2 interference.(A) Efficiency of NR5A2 siRNA mediated knockdown. (B) The mRNA expression of PRL and IGFBP1 after the knocking down of NR5A2. (C) The mRNA expression of WNT4 and BMP2 after the knocking down of NR5A2. (D) The mRNA expression of BMP2 and NR5A2 after the knocking down of BMP2. The data are expressed as the mean ± SEM. PRL, prolactin; IGFBP1, insulin-like growth factor binding protein 1; *P < 0.05; **P < 0.01; ***P < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0145968.g005: Molecular expression mechanism underlying the effect of NR5A2 interference.(A) Efficiency of NR5A2 siRNA mediated knockdown. (B) The mRNA expression of PRL and IGFBP1 after the knocking down of NR5A2. (C) The mRNA expression of WNT4 and BMP2 after the knocking down of NR5A2. (D) The mRNA expression of BMP2 and NR5A2 after the knocking down of BMP2. The data are expressed as the mean ± SEM. PRL, prolactin; IGFBP1, insulin-like growth factor binding protein 1; *P < 0.05; **P < 0.01; ***P < 0.001.
Mentions: To further elucidate the function of NR5A2 during the in vitro decidualization of hESCs, the level of NR5A2 mRNA in the cells was knocked down using RNA interference to silence endogenous NR5A2 expression. The siRNA targeting NR5A2 mRNA or a non-targeting siRNA were transfected into hESCs for 24 h and then subjected to differentiation. Fig 5A showed that the hESCs transfected with NR5A2 siRNA exhibited a reduction of almost 90% in NR5A2 mRNA expression compared to that of the cells transfected with control siRNA. This down-regulation of NR5A2 expression in hESCs resulted in a significant reduction in the expression of mRNAs corresponding to PRL and IGFBP1 (Fig 5B).

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