ORCID Profile
0000-0003-4270-6282
Current Organisations
Murdoch Children's Research Institute
,
University of Central Lancashire
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Publisher: American Physiological Society
Date: 11-2023
Publisher: Frontiers Media SA
Date: 22-12-2022
DOI: 10.3389/FCELL.2022.1078096
Abstract: A series of cyclical events within the uterus are crucial for pregnancy establishment. These include endometrial regeneration following menses, under the influence of estrogen (proliferative phase), then endometrial differentiation driven by estrogen rogesterone (secretory phase), to provide a microenvironment enabling attachment of embryo (as a hatched blastocyst) to the endometrial epithelium. This is followed by invasion of trophectodermal cells (the outer layer of the blastocyst) into the endometrium tissue to facilitate intrauterine development. Small extracellular vesicles (sEVs) released by endometrial epithelial cells during the secretory phase have been shown to facilitate trophoblast invasion however, the molecular mechanisms that underline this process remain poorly understood. Here, we show that density gradient purified sEVs (1.06–1.11 g/ml, Alix + and TSG101 + , ∼180 nm) from human endometrial epithelial cells (hormonally primed with estrogen and progesterone vs. estrogen alone) are readily internalized by a human trophectodermal stem cell line and promote their invasion into Matrigel matrix. Mass spectrometry-based proteome analysis revealed that sEVs reprogrammed trophectoderm cell proteome and their cell surface proteome (surfaceome) to support this invasive phenotype through upregulation of pro-invasive regulators associated with focal adhesions (NRP1, PTPRK, ROCK2, TEK), embryo implantation (FBLN1, NIBAN2, BSG), and kinase receptors (EPHB4/B2, ERBB2, STRAP). Kinase substrate prediction highlighted a central role of MAPK3 as an upstream kinase regulating target cell proteome reprogramming. Phosphoproteome analysis pinpointed upregulation of MAPK3 T204/T202 phosphosites in hTSCs following sEV delivery, and that their pharmacological inhibition significantly abrogated invasion. This study provides novel molecular insights into endometrial sEVs orchestrating trophoblast invasion, highlighting the microenvironmental regulation of hTSCs during embryo implantation.
Publisher: American Thoracic Society
Date: 05-06-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
DOI: 10.1161/STROKEAHA.112.671743
Abstract: Different modes of administration are used to collect stroke outcomes, even within the same study, potentially leading to different results. We investigated the effect of administration mode (postal questionnaire face-to-face interview) on self-reports of activities of daily living and mood. The study was nested within a poststroke motivational interviewing trial. Activities of daily living (Barthel Nottingham Extended) and mood (General Health Questionnaire Yale) were collected at 3 and 12 months via postal questionnaire. Participants were approached to respond again via face-to-face interview. Paired t tests (McNemar test) and intraclass correlation coefficients (Cohen κ) were used, with 95% CI, to compare scores (items). Forty-four participants consented. Only Barthel scores were significantly different they were 1.0 (95% CI, 0.5–1.6) higher face-to-face. The intraclass correlation coefficient for the Barthel was 0.90 for the other scales it was between 0.83 and 0.87. The Yale κ was 0.72. Modes of administration might be used interchangeably, albeit in conjunction with corrections for the Barthel.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Springer US
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 17-08-2023
DOI: 10.1038/S41390-023-02781-1
Abstract: Inhomogeneous lung aeration is a significant contributor to preterm lung injury. EIT detects inhomogeneous aeration in the research setting. Whether LUS detects inhomogeneous aeration is unknown. The aim was to determine whether LUS detects regional inhomogeneity identified by EIT in preterm lambs. LUS and EIT were simultaneously performed on mechanically ventilated preterm lambs. LUS images from non-dependent and dependent regions were acquired and reported using a validated scoring system and computer-assisted quantitative LUS greyscale analysis (Q-LUS MGV ). Regional inhomogeneity was calculated by observed over predicted aeration ratio from the EIT reconstructive model. LUS scores and Q-LUS MGV were compared with EIT aeration ratios using one-way ANOVA. LUS was performed in 32 lambs (~125d gestation, 128 images). LUS scores were greater in upper anterior (non-dependent) compared to lower lateral (dependent) regions of the left (3.4 vs 2.9, p = 0.1) and right (3.4 vs 2.7, p 0.0087). The left and right upper regions also had greater LUS scores compared to right lower (3.4 vs 2.7, p 0.0087) and left lower (3.7 vs 2.9, p = 0.1). Q-LUS MGV yielded similar results. All LUS findings corresponded with EIT regional differences. LUS may have potential in measuring regional aeration, which should be further explored in human studies. Inhomogeneous lung aeration is an important contributor to preterm lung injury, however, tools detecting inhomogeneous aeration at the bedside are limited. Currently, the only tool clinically available to detect this is electrical impedance tomography (EIT), however, its use is largely limited to research. Lung ultrasound (LUS) may play a role in monitoring lung aeration in preterm infants, however, whether it detects inhomogeneous lung aeration is unknown. Visual LUS scores and mean greyscale image analysis using computer assisted quantitative LUS (Q-LUS MGV ) detects regional lung aeration differences when compared to EIT. This suggests LUS reliably detects aeration inhomogeneity warranting further investigation in human trials.
Publisher: Wiley
Date: 19-03-2021
Abstract: Endometrial extracellular vesicles (EVs) are emerging as important players in reproductive biology. However, how their proteome is regulated throughout the menstrual cycle is not known. Such information can provide novel insights into biological processes critical for embryo development, implantation, and successful pregnancy. Using mass spectrometry‐based quantitative proteomics, we show that small EVs (sEVs) isolated from uterine lavage of fertile women (UL‐sEV), compared to infertile women, are laden with proteins implicated in antioxidant activity (SOD1, GSTO1, MPO, CAT). Functionally, sEVs derived from endometrial cells enhance antioxidant function in trophectoderm cells. Moreover, there was striking enrichment of invasion‐related proteins (LGALS1/3, S100A4/11) in fertile UL‐sEVs in the secretory (estrogen plus progesterone‐driven, EP) versus proliferative (estrogen‐driven, E) phase, with several players downregulated in infertile UL‐sEVs. Consistent with this, sEVs from EP‐ versus E‐primed endometrial epithelial cells promote invasion of trophectoderm cells. Interestingly, UL‐sEVs from fertile versus infertile women carry known players redictors of embryo implantation (PRDX2, IDHC), endometrial receptivity (S100A4, FGB, SERPING1, CLU, ANXA2), and implantation success (CAT, YWHAE, PPIA), highlighting their potential to inform regarding endometrial status regnancy outcomes. Thus, this study provides novel insights into proteome reprograming of sEVs and soluble secretome in uterine fluid, with potential to enhance embryo implantation and hence fertility.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Monique Fatmous.