Abstract
Decidualization is a morphological and biochemical transformation of endometrial stromal fibroblast into differentiated decidual cells, which is critical for embryo implantation and pregnancy establishment. The complex regulatory networks have been elucidated at both the transcriptome and the proteome levels, however very little is known about the post-transcriptional regulation of this process. miRNAs regulate multiple physiological pathways and their de-regulation is associated with human disorders including gynaecological conditions such as endometriosis and preeclampsia. In this study we profile the miRNAs expression throughout human endometrial stromal (hESCs) decidualization and analyze the requirement of the miRNA biogenesis enzyme Dicer during this process. A total of 26 miRNAs were upregulated and 17 miRNAs downregulated in decidualized hESCs compared to non-decidualized hESCs. Three miRNAs families, miR-181, miR-183 and miR-200, are down-regulated during the decidualization process. Using miRNAs target prediction algorithms we have identified the potential targets and pathways regulated by these miRNAs. The knockdown of Dicer has a minor effect on hESCs during in vitro decidualization. We have analyzed a battery of decidualization markers such as cell morphology, Prolactin, IGFBP-1, MPIF-1 and TIMP-3 secretion as well as HOXA10, COX2, SP1, C/EBPß and FOXO1 expression in decidualized hESCs with decreased Dicer function. We found decreased levels of HOXA10 and altered intracellular organization of actin filaments in Dicer knockdown decidualized hESCs compared to control. Our results provide the miRNA signature of hESC during the decidualization process in vitro. We also provide the first functional characterization of Dicer during human endometrial decidualization although surprisingly we found that Dicer plays a minor role regulating this process suggesting that alternative biogenesis miRNAs pathways must be involved in human endometrial decidualization.
Highlights
Implantation of the human embryo in the maternal endometrium is a key step for the successful establishment of pregnancy and requires a dialog between the competent embryo and the receptive endometrium [1]
Human endometrial stromal cells were isolated as previously described [20]. hESCs were cultured in DMEM/F12 medium containing 10% charcoal stripped fetal bovine serum (FBS) and 0.1% antibiotics. hESCs obtained from 20 different biopsies were plated in 6-well plates
This study describes the miRNA signature during human endometrial stromal in vitro decidualization and analyzes the role of Dicer, a major component of miRNA biogenesis machinery, during this process
Summary
Implantation of the human embryo in the maternal endometrium is a key step for the successful establishment of pregnancy and requires a dialog between the competent embryo and the receptive endometrium [1]. Stromal decidualization is a critical endometrial process that allows correct trophoblast invasion and placenta formation [2]. In humans, this process is initiated independently of pregnancy, and includes morphological and biochemical changes of the fibroblast-like stromal cells by the action of ovarian steroids 17b-estradiol (E2) and progesterone (P4). This process is initiated independently of pregnancy, and includes morphological and biochemical changes of the fibroblast-like stromal cells by the action of ovarian steroids 17b-estradiol (E2) and progesterone (P4) These changes involve extracellular matrix, cytoskeleton and vascular remodeling, secretory transformation of glands, influx of specialized immune cells and differentiation of the endometrial stromal cells into decidual cells [2]. Very little information is available about the post-transcriptional regulation of this process
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