The impact of infertility diagnosis on embryo-endometrial dialogue

Parks JC, Jason C. Parks, Blair R. McCallie, Alyssa L Patton, A.L. Patton, Patton AL, Al-Safi ZA, Zain Al-Safi, Zain A Al-Safi, Alex J. Polotsky, Polotsky AJ, Darren K. Griffin, Griffin DK, Schoolcraft WB, William B. Schoolcraft, Mandy G. Katz‐Jaffe, Katz-Jaffe MG, Mandy G Katz-Jaffe
Reproduction (Cambridge, England) · 2018 · vol. 155(6) , pp. 543–552 · doi:10.1530/rep-17-0566 · PMID:29636406 · W2797545036
Other OA: bronze CC0 ⤵ 1 in-corpus citation
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Advanced maternal age and endometriosis alter embryo-endometrial dialogue through extracellular vesicle miRNA dysregulation, impacting cell cycle and proliferation pathways.

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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.

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Condition tags

endometriosisinfertility

MeSH descriptors

Biomarkers Blastocyst Embryo Implantation Endometrium Gene Expression Regulation, Developmental Gene Expression Regulation, Developmental Infertility, Female Adult Adult Biomarkers Biomarkers Blastocyst Blastocyst Blastocyst Cells, Cultured Cells, Cultured Coculture Techniques Coculture Techniques Embryo Implantation Embryo Implantation

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (67)

Cited by (1)

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