Recent Insights into Human Endometrial Peptidases in Blastocyst Implantation via Shedding of Microvesicles

Abstract

Blastocyst implantation involves multiple interactions with numerous molecules expressed in endometrial epithelial cells (EECs) during the implantation window; however, there is limited information regarding the molecular mechanism underlying the crosstalk. In blastocysts, fibronectin plays a major role in the adhesion of various types of cells by binding to extracellular matrix proteins via the Arg-Gly-Asp (RGD) motif. In EECs, RGD-recognizing integrins are important bridging receptors for fibronectin, whereas the non-RGD binding of fibronectin includes interactions with dipeptidyl peptidase IV (DPPIV)/cluster of differentiation (CD) 26. Fibronectin may also bind to aminopeptidase N (APN)/CD13, and in the endometrium, these peptidases are present in plasma membranes and lysosomal membranes. Blastocyst implantation is accompanied by lysosome exocytosis, which transports various peptidases and nutrients into the endometrial cavity to facilitate blastocyst implantation. Both DPPIV and APN are released into the uterine cavity via shedding of microvesicles (MVs) from EECs. Recently, extracellular vesicles derived from endometrial cells have been proposed to act on trophectoderm cells to promote implantation. MVs are also secreted from embryonal stem cells and may play an active role in implantation. Thus, crosstalk between the blastocyst and endometrium via extracellular vesicles is a new insight into the fundamental molecular basis of blastocyst implantation.

Serum‐derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID‐19 patients

“…CD13, CD24, and CD82 are involved in inflammatory processes (Barkal et al., 2019; Lu et al., 2020; Yeung et al., 2018). CD13 is known receptor for several corona viruses (Devarakonda et al., 2021; Nomura et al., 2004; Pöhlmann et al., 2006; Qi et al., 2020) and associated with several EVs types, including ones from, that is, synoviocytes, endometrial epithelial cells, microglia, urine, plasma, leukocytes and umbilical cord‐derived mesenchymal stromal cells (Erdbrügger et al., 2021; Lin et al., 2020; Morgan et al., 2016; Priya et al., 2021; Potolicchio et al., 2005; Romanov et al., 2018; Tőkés‐Füzesi et al., 2018; Yoshihara et al., 2021). The tetraspanin CD82 is a constituent of tetraspanin‐enriched membrane domains (TEMs, which represent the places of entry/egress of some viruses) but also responsible for immune cells recruitment, migration (Yeung et al., 2018) and acts as a costimulatory molecule for T cells (Earnest et al., 2017; Florin & Lang, 2018; ProteinAtlas: CD82; Sims et al., 2018; Yáñez‐Mó et al., 2009).…”

Rhythm of the First Language: Dynamics of Extracellular Vesicle-Based Embryo–Maternal Communication in the Pre-Implantation Microenvironment

“…None of the genes showed any significant differential expression in the 48 h vs. 30 min comparison, indicating both the drastic nature of the transcriptomic changes seen at the 4 h time point and the fact that the endometrial transcriptome returned to a semblance of the base level after 48 hrs. All the selected genes were reported to regulate some critical function in embryo implantation, either as individual genes or as part of a pathway [ 49 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. Interestingly, none of the genes that were upregulated or downregulated in all three time points nor the pathways they enrich were mentioned regarding human embryo implantation in previous publications, to the best of our knowledge ( Supplementary File S4 ).…”

Local Immune Biomarker Expression Depending on the Uterine Microbiota in Patients with Idiopathic Infertility

“…Both a receptive endometrium and timely signaling between the blastocyst and endometrium determine the success of implantation [17]. For instance, such endometrial factors as calcitonin [18], lysophosphatidic acid (LPA) [19], heparin-binding epidermal growth factor (HB-EGF) [20], leukemia-inhibiting factor (LIF) [21], and epidermal growth factor (EGF) [16] promote embryo implantation. At the same time, the endometrium undergoes remodeling in response to a variety of factors secreted by the embryo, i.e., hCG [6], IL-1 [15], BMP2 [18], IGF1 [20], FGF2 [16], and WNT [22].…”