title: Downregulation of A(1) and A(2B) adenosine receptors in human trisomy 21 mesenchymal cells from first-trimester chorionic villi.
abstract: Human reproduction is complex and prone to failure. Though causes of miscarriage remain unclear, adenosine, a proangiogenic nucleoside, may help determine pregnancy outcome. Although adenosine receptor (AR) expression has been characterized in euploid pregnancies, no information is available for aneuploidies, which, as prone to spontaneous abortion (SA), are a potential model for shedding light on the mechanism regulating this event. AR expression was investigated in 71 first-trimester chorionic villi (CV) samples and cultured mesenchymal cells (MC) from euploid and TR21 pregnancies, one of the most frequent autosomal aneuploidy, with a view to elucidating their potential role in the modulation of vascular endothelial growth factor (VEGF) and nitric oxide (NO). Compared to euploid cells, reduced A(1) and A(2B) expression was revealed in TR21 CV and MCs. The non-selective adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased NO, by activating, predominantly, A(1)AR and A(2A)AR through a molecular pathway involving hypoxia-inducible-factor-1 (HIF-1α), and increased VEGF, mainly through A(2B). In conclusion the adenosine transduction cascade appears to be disturbed in TR21 through reduced expression of A(2B) and A(1)ARs. These anomalies may be implicated in complications such as fetal growth restriction, malformation and/or SA, well known features of aneuploid pregnancies. Therefore A(1) and A(2B)ARs could be potential biomarkers able to provide an early indication of SA risk and their stimulation may turn out to improve fetoplacental perfusion by increasing NO and VEGF.
authors.affiliation: Department of Clinical and Experimental Medicine, Pharmacology Unit and Interdisciplinary Center for the Study of Inflammation, University of Ferrara, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gessi
authors.forename: Stefania
authors.initials: S
authors.lastname: Merighi
authors.forename: Angela
authors.initials: A
authors.lastname: Stefanelli
authors.forename: Prisco
authors.initials: P
authors.lastname: Mirandola
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bonfatti
authors.forename: Sergio
authors.initials: S
authors.lastname: Fini
authors.forename: Alberto
authors.initials: A
authors.lastname: Sensi
authors.forename: Roberto
authors.initials: R
authors.lastname: Marci
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
authors.forename: Fortunato
authors.initials: F
authors.lastname: Vesce
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics / Q000378:metabolism; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000782:Aneuploidy; D002824:Chorionic Villi / Q000378:metabolism; D004314:Down Syndrome / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D011261:Pregnancy Trimester, First / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D043682:Receptor, Adenosine A1; D043704:Receptor, Adenosine A2B; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D019830:Adenosine-5'-(N-ethylcarboxamide)