Requirement of heart and neural crest derivatives–expressed transcript 2 during decidualization of human endometrial stromal cells in vitro

Shindoh, Hisayuu; Okada, Hidetaka; Tsuzuki, Tomoko; Nishigaki, Akemi; Kanzaki, Hideharu

doi:10.1016/j.fertnstert.2014.03.013

Cited by 33 publications

(39 citation statements)

References 37 publications

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“…Recent studies have revealed that decidual morphological changes are associated with the increased expression of connexin‐43 (CX43), a major gap junction protein, and that the loss of CX43 expression resulted in an aberrant differentiation of the uterine stromal cells . In accordance herewith, it was found that HAND2 knockdown significantly reduced CX43 protein expression in ESCs . These results suggest that HAND2 contributes to the increased CX43 levels that are involved in the formation of gap junctions during decidualization.…”

Section: Functions Of Decidualizationsupporting

confidence: 83%

“…However, recent studies have demonstrated that several genes in human ESCs are specifically upregulated by progestin, but not by cAMP. 29,32,33 These results suggest that there is an interesting disparity between the progestin and cAMP regulatory pathways during the decidualization of human ESCs.…”

Section: Regulation Of and Molecular Mechanisms During Decidualizmentioning

confidence: 80%

“…The current authors recently reported that HAND2 is required for progestin-induced FBLN1 mRNA and protein expression in human ESCs. 33 These results suggest that HAND2 is an essential downstream target of the progesterone pathway to induce FBLN1 in…”

Section: Extracellular Matrix Remodelingmentioning

confidence: 83%

“…In cultured ESCs, treatment with cAMP alone increases PRL expression, which is further elevated in the presence of both cAMP and progestin. However, recent studies have demonstrated that several genes in human ESCs are specifically upregulated by progestin, but not by cAMP . These results suggest that there is an interesting disparity between the progestin and cAMP regulatory pathways during the decidualization of human ESCs.…”

Section: Regulation Of and Molecular Mechanisms During Decidualizationmentioning

confidence: 92%

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Decidualization of the human endometrium

Okada

Tsuzuki

Murata

2018

Reprod Medicine & Biology

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252

176

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BackgroundDecidualization of the human endometrium, which involves a dramatic morphological and functional differentiation of human endometrial stromal cells (ESCs), is essential for the establishment of a successful pregnancy. Decidualization results from a complex interplay of transcription factors, morphogens, cytokines, cell cycle regulators, and signaling pathways.MethodsBased on a literature review, the regulation of, and the molecular mechanisms involved in, the decidualization of the endometrium are described.Main findingsProgesterone, together with proteins that are regulated by progesterone and/or cyclic adenosine monophosphate, including homeobox A10, forkhead box O1, signal transducers and activators of transcription, and heart and neural crest derivatives expressed transcript 2, forms a critical network for ESC decidualization and is a prerequisite to successful implantation. Decidualized ESCs contribute to the microenvironment at the feto–maternal interface and its direct or indirect influence on extracellular matrix remodeling, regulation of the local immune response, anti‐oxidative stress, and angiogenesis (vascular maturation). Impairment of this process is associated with a variety of pregnancy disorders, including infertility, recurrent miscarriages, and uteroplacental disorders.ConclusionA deeper understanding of the process of decidualization is expected to provide new insights into the fields of reproductive biology and reproductive medicine.

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Section: Functions Of Decidualizationsupporting

confidence: 83%

Section: Regulation Of and Molecular Mechanisms During Decidualizmentioning

confidence: 80%

Section: Extracellular Matrix Remodelingmentioning

confidence: 83%

Section: Regulation Of and Molecular Mechanisms During Decidualizationmentioning

confidence: 92%

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Decidualization of the human endometrium

Okada

Tsuzuki

Murata

2018

Reprod Medicine & Biology

Self Cite

252

176

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“…DAVID analysis revealed that the direct PGR target genes enriched biological themes for regulation of cell motion, vascular development, and intracellular cascade (Table 3). Among the known direct PGR target genes involved in decidualization, we observed PGR binding and differential regulation in several genes such as FK506 binding protein 5 (FKBP5), heart-and neural crest derivatives-expressed protein 2 (HAND2), and cysteine-rich angiogenic inducer 61 (CYR61) (29,30). ChIP-seq did not identify binding of PGR to the promoter of IGFBP1, a finding that was inconsistent with previous reports that demonstrated progesterone-responsive regulation of promoter activity (31).…”

Section: Identification Of Pgr Global Genomic Binding Sites In Hescs mentioning

confidence: 99%

Progesterone Receptor Transcriptome and Cistrome in Decidualized Human Endometrial Stromal Cells

Mazur¹,

Vasquez

et al. 2015

Endocrinology

114

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Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma that is required to establish and support pregnancy. Progesterone acting via its nuclear receptor, the progesterone receptor (PGR), is a critical regulator of decidualization and is known to interact with certain members of the activator protein-1 (AP-1) family in the regulation of transcription. In this study, we identified the cistrome and transcriptome of PGR and identified the AP-1 factors FOSL2 and JUN to be regulated by PGR and important in the decidualization process. Direct targets of PGR were identified by integrating gene expression data from RNA sequencing with the whole-genome binding profile of PGR determined by chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) in primary human endometrial stromal cells exposed to 17β-estradiol, medroxyprogesterone acetate, and cAMP to promote in vitro decidualization. Ablation of FOSL2 and JUN attenuates the induction of 2 decidual marker genes, IGFBP1 and PRL. ChIP-seq analysis of genomic binding revealed that FOSL2 is bound in proximity to 8586 distinct genes, including nearly 80% of genes bound by PGR. A comprehensive assessment of the PGR-dependent decidual transcriptome integrated with the genomic binding of PGR identified FOSL2 as a potentially important transcriptional coregulator of PGR via direct interaction with regulatory regions of genes actively regulated during decidualization.

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