FoxM1 Directs STAT3 Expression Essential for Human Endometrial Stromal Decidualization

Jiang, Yaling; Liao, Yixin; He, Hui; Xin, Qiliang; Tu, Z. C.; Kong, Shuangbo; Cui, Tongtong; Wang, Bingyan; Song, Qisheng; Li, Bing; Zhang, Shuang; Wang, Haibin

doi:10.1038/srep13735

Cited by 35 publications

(26 citation statements)

References 39 publications

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“…Forkhead box protein O3A ( FOXO3A ) was shown to be down-regulated upon decidualization, whereas forkhead box protein O4 ( FOXO4 ) is not expressed in the endometrium [ 53 ]. On the other hand, we confirmed the up-regulation of STAT3 upon decidualization [ 54 ], but failed to show its regulation by insulin, suggesting that the effect of insulin was specific to FOXO1 . It was also shown that inhibition of FOXM1 could prevent decidualization [ 54 ], while insulin could not in our experiments.…”

Section: Discussionmentioning

confidence: 58%

“…On the other hand, we confirmed the up-regulation of STAT3 upon decidualization [ 54 ], but failed to show its regulation by insulin, suggesting that the effect of insulin was specific to FOXO1 . It was also shown that inhibition of FOXM1 could prevent decidualization [ 54 ], while insulin could not in our experiments. These observations further suggest that insulin does not inhibit the activity of FOXM1 in decidualizing stromal cells.…”

Section: Discussionmentioning

confidence: 58%

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Dysregulation of In Vitro Decidualization of Human Endometrial Stromal Cells by Insulin via Transcriptional Inhibition of Forkhead Box Protein O1

et al. 2017

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Insulin resistance and compensatory hyperinsulinemia are characteristic features of obesity and polycystic ovary syndrome, and both are associated with reduced fertility and implantation. There is little knowledge about the effect of insulin on the decidualization process and previous findings are contradictory. We investigated the effect of insulin on the regulation of forkhead box protein O1 (FOXO1), one of the most important transcription factors during decidualization. Endometrial stromal cells were isolated from six healthy, regularly menstruating women and decidualized in vitro. Gene expression levels of six putative FOXO1 target genes (including insulin-like growth factor binding protein-1 (IGFBP1) and prolactin (PRL)) were measured with Real-Time PCR following FOXO1 inhibition or insulin treatment. PI3K inhibition was used to identify the possible mechanism behind regulation. Subcellular localization of FOXO1 was analyzed with immunofluorescence. All the genes (IGFBP1, CTGF, INSR, DCN, LEFTY2), except prolactin, were evaluated as FOXO1 target genes in decidualizing stromal cells. Insulin caused a significant dose-dependent inhibition of the verified FOXO1 target genes. It was also demonstrated that insulin regulated FOXO1 target genes by transcriptional inactivation and nuclear export of FOXO1 via PI3K pathway. However, insulin did not inhibit the morphological transformation of endometrial stromal cells via transcriptional inactivation of FOXO1. This study provides new insights on the action of insulin on the endometrium via regulation of FOXO1. It is suggested that hyperinsulinemia results in dysregulation of a high number of FOXO1 controlled genes that may contribute to endometrial dysfunction and reproductive failure. Our findings may illuminate possible reasons for unexplained infertility.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 58%

Dysregulation of In Vitro Decidualization of Human Endometrial Stromal Cells by Insulin via Transcriptional Inhibition of Forkhead Box Protein O1

et al. 2017

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“…A recent genomic study using these cells identified P response element in the HOXA10 gene promoter, implying that HOXA10 is a direct target of PR in endometrial stromal cells . Interestingly, it has been reported recently that FoxM1 functions downstream of Hoxa10 to control stromal cell proliferation in the mouse and it directs the expression of STAT3 during human endometrial stromal cell differentiation …”

Section: Control Of Uterine Receptivity and Decidualization By Pr‐regmentioning

confidence: 99%

Progesterone‐Regulated Endometrial Factors Controlling Implantation

Bhurke

Bagchi

2016

American J Rep Immunol

132

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The steroid hormone progesterone (P), acting via the progesterone receptor (PR) isoforms, PR-A and PR-B, exerts a profound influence on uterine functions during early gestation. In recent years, chromatin immunoprecipitation-sequencing in combination with microarray-based gene expression profiling analyses have revealed that the PR isoforms control a substantially large cistrome and transcriptome during endometrial differentiation in the human and the mouse. Genetically engineered mouse models have established that several PR-regulated genes, such as Ihh, Bmp2, Hoxa10, and Hand2, are essential for implantation and decidualization. PR-A and PR-B also collaborate with other transcription factors, such as FOS, JUN, C/EBPβ and STAT3, to regulate the expression of many target genes that function in concert to properly control uterine epithelial proliferation, stromal differentiation, angiogenesis, and local immune response to render the uterus ‘receptive’ and allow embryo implantation. This review article highlights recent work describing the key PR-regulated pathways that govern critical uterine functions during establishment of pregnancy.

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“…Decidualization stimuli such as oestrogen, progesterone, and cAMP specifically upregulate STAT3 [ 75 , 76 ] and STAT5 [ 71 ] in endometrial stromal cells. In vivo STAT3 is maximally expressed in glandular epithelium during the secretory phase and in decidual cells during late-secretory phase [ 76 ].…”

Section: Human Decidual Development and Structurementioning

confidence: 99%

Human Decidual Stromal Cells as a Component of the Implantation Niche and a Modulator of Maternal Immunity

Vinketova

Mourdjeva

Oreshkova

2016

Journal of Pregnancy

112

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The human decidua is a specialized tissue characterized by embryo-receptive properties. It is formed during the secretory phase of menstrual cycle from uterine mucosa termed endometrium. The decidua is composed of glands, immune cells, blood and lymph vessels, and decidual stromal cells (DSCs). In the process of decidualization, which is controlled by oestrogen and progesterone, DSCs acquire specific functions related to recognition, selection, and acceptance of the allogeneic embryo, as well as to development of maternal immune tolerance. In this review we discuss the relationship between the decidualization of DSCs and pathological obstetrical and gynaecological conditions. Moreover, the critical influence of DSCs on local immune cells populations as well as their relationship to the onset and maintenance of immune tolerance is described.

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FoxM1 Directs STAT3 Expression Essential for Human Endometrial Stromal Decidualization

Cited by 35 publications

References 39 publications

Dysregulation of In Vitro Decidualization of Human Endometrial Stromal Cells by Insulin via Transcriptional Inhibition of Forkhead Box Protein O1

Dysregulation of In Vitro Decidualization of Human Endometrial Stromal Cells by Insulin via Transcriptional Inhibition of Forkhead Box Protein O1

Progesterone‐Regulated Endometrial Factors Controlling Implantation

Human Decidual Stromal Cells as a Component of the Implantation Niche and a Modulator of Maternal Immunity

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