Search

Abstract: Implantation is the first maternal–embryo crosstalk that only occurs during a finite period called the ‘implantation window’. HOXA10, a homeobox transcription factor, plays an important regulatory role during this period. However, the target genes of HOXA10 involved in implantation and decidualization have not been identified. Using a chromatin immunoprecipitation screen, we identified the p300/CBP-associated factor (p/CAF) as a direct HOXA10 target gene in vivo. Adenovirus-mediated overexpression and siRNA-specific knockdown of HOXA10 altered p/CAF promoter activity via interaction with the three consecutive TTAT element units in human endometrial cells. These results indicate that p/CAF is a novel HOXA10 target gene, and HOXA10 promotes human endometrial development, at least in part, through the regulation of p/CAF gene. [Copyright &y& Elsevier]

Highlights: [•] Matrix metalloproteinase-26 (MMP-26) is a novel downstream target gene of HOXA10 in human endometrial cells. [•] HOXA10 binds directly to a conserved TTAT unit (−442 to −439) of the MMP-26 gene promoter. [•] HOXA10 is required for hormone-induced MMP-26 expression and secretion. [•] HOXA10-mediated expression of MMP-26 promotes embryo adhesion. [ABSTRACT FROM AUTHOR]

Abstract: Members of the KLFs family of transcription factors play roles in maternal endometrium development during embryo implantation. However, the specific role of KLF12 in endometrium development has not yet been described. In this study, we showed that KLF12 expression in human endometrial stromal cells (HESCs) was significantly decreased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). The adenovirus-mediated overexpression of KLF12 in HESCs significantly repressed the expression and secretion of decidualization biomarker genes and their products decidual prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1) induced by 8-Br-cAMP and MPA. Moreover, CHIP and luciferase reporter assays demonstrated that KLF12 bound to a CAGTGGG element within the decidual prolactin promoter and decreased decidual PRL promoter (dPRL/-2000Luc) activation in a sequence-specific manner. Taken together, these findings suggest KLF12 is a negative regulator of human endometrial stromal cell decidualization. [Copyright &y& Elsevier]

Abstract: Prolactin (PRL) is synthesized and released by several extrapituitary tissues, including decidualized stromal cells. Despite the important role of decidual PRL during pregnancy, little is understood about the factors involved in the proper regulation of decidual PRL expression. Here we present evidence that the transcription factor Nur77 plays an active role in decidual prolactin expression in human endometrial stromal cells (hESCs). Nur77 mRNA expression in hESCs was significantly increased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). Adenovirus-mediated overexpression of Nur77 in hESCs markedly increased PRL mRNA expression and enhanced decidual PRL promoter (dPRL/−332Luc) activity in a concentration-dependent manner. Furthermore, knockdown of Nur77 in hESCs significantly decreased decidual PRL promoter activation and substantially attenuated PRL mRNA expression and PRL secretion (P <0.01) induced by 8-Br-cAMP and MPA. These results demonstrate that Nur77 is a novel transcription factor that contributes significantly to the regulation of prolactin gene expression in human endometrial stromal cells. [ABSTRACT FROM AUTHOR]