Abstract
BackgroundDecidualization is a prerequisite for successful implantation and the establishment of pregnancy. Krüppel-like factor 12 (KLF12) is a negative regulator of endometrial decidualization in vitro. We investigated whether KLF12 was associated with impaired decidualization under conditions of repeated implantation failure (RIF).MethodsUterine tissues were collected from a mouse model of early pregnancy and artificial decidualization for immunohistochemistry, Western blot and real-time PCR analysis. Reporter gene assays, chromatin immunoprecipitation-PCR and avidin-biotin conjugate DNA precipitation assays were performed to analyze the transcriptional regulation of forkhead box O1 (FOXO1) by KLF12. Furthermore, the protein levels of KLF12 and FOXO1 in patients with RIF were analyzed by Western blot and immunohistochemistry.ResultsKLF12 led to defective implantation and decidualization in the mouse uterine model of early pregnancy and artificial decidualization by directly binding to the FOXO1 promoter region and inhibiting its expression in human endometrial stromal cells. Elevated KLF12 expression was accompanied by decreased FOXO1 expression in the endometria of patients with RIF.ConclusionsAs a novel regulator, KLF12 predominantly controls uterine endometrial differentiation during early pregnancy and leads to implantation failure.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-015-0079-z) contains supplementary material, which is available to authorized users.
Highlights
Decidualization is a prerequisite for successful implantation and the establishment of pregnancy
We have previously demonstrated that Krüppel-like factor 12 (KLF12) is expressed in the glandular epithelium (GE) and stromal cells of secretory phase endometrial tissue and that it negatively regulates endometrial decidualization and marker gene transcription [14]
The uterine lumens of ICR mice were injected with a KLF12-expressing adenovirus (AdFlag-KLF12) or Ad-LacZ on 1.5 dpc (Fig. 1a), and the implantation status was examined on 4.5 dpc to determine whether KLF12 was a critical regulator of embryo implantation
Summary
Decidualization is a prerequisite for successful implantation and the establishment of pregnancy. Krüppel-like factor 12 (KLF12) is a negative regulator of endometrial decidualization in vitro. Stromal decidualization in the endometrium is crucial for successful embryo implantation and the maintenance of pregnancy. This process is defined by the mesenchymalto-epithelial transformation of endometrial fibroblasts and stromal cells into secretory epithelioid decidual cells, which affect endometrial receptivity [1]. Sun et al reported that a zinc fingercontaining transcription factor, Krüppel-like factor 5 (KLF5), is expressed dynamically in the luminal epithelium and stroma throughout peri-implantation. We have previously demonstrated that KLF12 is expressed in the glandular epithelium (GE) and stromal cells of secretory phase endometrial tissue and that it negatively regulates endometrial decidualization and marker gene transcription [14]
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