Human S100A10 plays a crucial role in the acquisition of the endometrial receptivity phenotype

Abstract

In assisted reproduction, about 30% of embryo implantation failures are related to inadequate endometrial receptivity. To identify molecules involved in endometrial receptivity acquisition, we investigated, using a SELDI-TOF approach, the protein expression profile of early-secretory and midsecretory endometrium samples. Among the proteins upregulated in mid-secretory endometrium, we investigated the function of S100A10 in endometrial receptivity and implantation process. S100A10 was expressed in epithelial and stromal cells of the endometrium of fertile patients during the implantation windows. Conversely, it was downregulated in the mid-secretory endometrium of infertile patients diagnosed as non-receptive. Transcriptome analysis of human endometrial epithelial and stromal cells where S100A10 was silenced by shRNA revealed the deregulation of 37 and 256 genes, respectively, related to components of the extracellular matrix and intercellular connections. Functional annotations of these deregulated genes highlighted alterations of the leukocyte extravasation signaling and angiogenesis pathways that play a crucial role during implantation. S100A10 silencing also affected the migration of primary endometrial epithelial and stromal cells, decidualization and secretory transformation of primary endometrial stromal cells and epithelial cells respectively, and promoted apoptosis in serum-starved endometrial epithelial cells. Our findings identify S100A10 as a player in endometrial receptivity acquisition.

Human Endometrial Extracellular Vesicles Functionally Prepare Human Trophectoderm Model for Implantation: Understanding Bidirectional Maternal‐Embryo Communication

“…Additionally, we report several known regulators of implantation, including AHNAK, S100A10, and PLAT, and human trophectoderm markers important in early implantation including cathepsin CTSC, actin ACTA2, and phosphoglucomutase 1 (PGM1) ( Table ). EpCAM (CD326) has been implicated for differentiation and survival of parietal trophoblast cells, normal development of the placental labyrinth, and establishment of a competent maternal–fetal circulation .…”

S100 protein family and embryo implantation

“…In receptive human endometrial samples, the expression of S100A10 increases during WOI. They also proved that in the nonreceptive samples, mRNA level of this protein is significantly decreased . Apoptosis plays a very important role in endometriosis during WOI, and failure of this signaling pathway (due to the reduction of S100A10 expression) can be a reason for repeated implantation failure (RIF) .…”

“…Understanding of involved molecular mechanisms in achieving of endometrial receptivity phenotype will help in the success of ART. It has been reported different expression of S100A10 in a proteomic analysis of endometrial samples . Based on the results of the proteomic analysis, it seems that S100A10 protein plays effective and important role, and for this reason we focus more on this protein …”

“…S100A10 silencing inhibits prolactin secretion in human embryonic stem cells. But significantly increases prolactin in human endometrial epithelial cells and still the molecular mechanism that S100A10 defection caused by it on different expressions of prolactin, not thoroughly known …”

S100 proteins

“…A study on transcriptome-based analysis in equine pregnancy revealed that S100A6 protein was expressed in conceptus side, and S100A2, S100A4, S100A6 and S100A8 were present in maternal endometrium on day 16 in mare 59 . A key role of these proteins has been suggested in epidermal growth factor-stimulated embryo adhesion, acquisition of endometrial receptivity, immunotolerance, apoptosis of dead endometrial epithelial cells and prolactin secretion, a marker for onset of decidualization 60 61 . S100 β protein is also found to be up regulated in trisomy cases, and their upregulation is an indicator of a brain lesion in developing foetus 58 .…”