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The impact of infertility diagnosis on embryo-endometrial dialogue

Parks, Jason C, McCallie, Blair R, Patton, Alyssa L, Al-Safi, Zain A, Polotsky, Alex J, Griffin, Darren K., Schoolcraft, William B, Katz-Jaffe, Mandy G (2018) The impact of infertility diagnosis on embryo-endometrial dialogue. Reproduction, 155 (6). pp. 543-552. ISSN 1470-1626. (doi:10.1530/REP-17-0566) (KAR id:67206)

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Abstract

Initial stages of implantation involve bi-directional molecular crosstalk between the blastocyst and endometrium. This study investigated an association between infertility etiologies, specifically advanced maternal age (AMA) and endometriosis, on the embryo-endometrial molecular dialogue prior to implantation. Co-culture experiments were performed with endometrial epithelial cells (EEC) and cryopreserved day 5 blastocysts (n?=?41???Grade 3BB) donated from patients presenting with AMA or endometriosis, compared to fertile donor oocyte controls. Extracellular vesicles isolated from co-culture supernatant were analyzed for miRNA expression and revealed significant alterations correlating to AMA or endometriosis. Specifically, AMA resulted in 16 miRNAs with increased expression (P???0.05) and strong evidence for negative regulation toward 206 target genes. VEGFA, a known activator of cell adhesion, displayed decreased expression (P???0.05), validating negative regulation by 4 of these increased miRNAs: miR-126; 150; 29a; 29b (P???0.05). In endometriosis patients, a total of 10 significantly altered miRNAs displayed increased expression compared to controls (miR-7b; 9; 24; 34b; 106a; 191; 200b; 200c; 342-3p; 484) (P???0.05), targeting 1014 strong evidence-based genes. Three target genes of miR-106a (CDKN1A, E2F1 and RUNX1) were independently validated. Functional annotation analysis of miRNA-target genes revealed enriched pathways for both infertility etiologies, including disrupted cell cycle regulation and proliferation (P???0.05). These extracellular vesicle-bound secreted miRNAs are key transcriptional regulators in embryo-endometrial dialogue and may be prospective biomarkers of implantation success. One of the limitations of this study is that it was a stimulated, in vitro model and therefore may not accurately reflect the in-vivo environment.

Item Type: Article
DOI/Identification number: 10.1530/REP-17-0566
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Sue Davies
Date Deposited: 05 Jun 2018 15:06 UTC
Last Modified: 23 Jan 2020 04:14 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/67206 (The current URI for this page, for reference purposes)
Griffin, Darren K.: https://orcid.org/0000-0001-7595-3226
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