Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density.
annexin-A4
cerebral cavernous malformation protein 3
cerebral cortex
ethanol
fetal alcohol spectrum disorder
placenta
Journal
Frontiers in neuroscience
ISSN: 1662-4548
Titre abrégé: Front Neurosci
Pays: Switzerland
ID NLM: 101478481
Informations de publication
Date de publication:
2020
2020
Historique:
received:
10
12
2019
accepted:
27
04
2020
entrez:
14
7
2020
pubmed:
14
7
2020
medline:
14
7
2020
Statut:
epublish
Résumé
Jegou et al. (2012) have reported prenatal alcohol exposure (PAE)-induced reductions of angiogenesis-related proteins in mouse placenta. These effects were associated with striking alterations in microvascular development in neonatal cerebral cortex. Here, we employed a rat model of moderate PAE to search for additional proteins whose placental and fetal cortical expression is altered by PAE, along with a subsequent examination of fetal cerebral cortical alterations associated with altered protein expression. Long-Evans rat dams voluntarily consumed either a 0 or 5% ethanol solution 4 h each day throughout gestation. Daily ethanol consumption, which resulted in a mean peak maternal serum ethanol concentration of 60.8 mg/dL, did not affect maternal weight gain, litter size, or placental or fetal body weight. On gestational day 20, rat placental: fetal units were removed by Caesarian section. Placental protein expression, analyzed by 2D-PAGE - tandem mass spectroscopy, identified a total of 1,117 protein spots, 20 of which were significantly altered by PAE. To date, 14 of these PAE-altered proteins have been identified. Western blotting confirmed the alterations of two of these placental proteins, namely, annexin-A4 (ANX-A4) and cerebral cavernous malformation protein 3 (CCM-3). Specifically, PAE elevated ANX-A4 and decreased CCM-3 in placenta. Subsequently, these two proteins were measured in fetal cerebral cortex, along with radiohistochemical studies of VEGF binding and histofluorescence studies of microvascular density in fetal cerebral cortex. PAE elevated ANX-A4 and decreased CCM-3 in fetal cerebral cortex, in a pattern similar to the alterations observed in placenta. Further, both VEGF receptor binding and microvascular density and orientation, measures that are sensitive to reduced CCM-3 expression in developing brain, were significantly reduced in the ventricular zone of fetal cerebral cortex. These results suggest that the expression angiogenesis-related proteins in placenta might serve as a biomarker of ethanol-induced alterations in microvascular development in fetal brain.
Identifiants
pubmed: 32655346
doi: 10.3389/fnins.2020.00519
pmc: PMC7325964
doi:
Types de publication
Journal Article
Langues
eng
Pagination
519Subventions
Organisme : NIAAA NIH HHS
ID : P20 AA017068
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA015420
Pays : United States
Informations de copyright
Copyright © 2020 Savage, Rosenberg, Coquet, Porch, Allen, Roux, Aligny, Jouenne and Gonzalez.
Références
J Pediatr. 1978 Mar;92(3):457-60
pubmed: 632992
J Cell Mol Med. 2013 Mar;17(3):407-18
pubmed: 23388056
Alcohol Clin Exp Res. 2010 Oct;34(10):1793-802
pubmed: 20626729
J Neurobiol. 2006 Feb 15;66(3):236-42
pubmed: 16329123
Clin Epigenetics. 2018 Jan 12;10:5
pubmed: 29344313
Alcohol Clin Exp Res. 2016 Apr;40(4):826-37
pubmed: 27038596
Alcohol. 2019 May;76:47-57
pubmed: 30557779
Nat Neurosci. 2016 Feb;19(2):253-62
pubmed: 26752160
J Neurosci. 2013 Sep 11;33(37):14809-15
pubmed: 24027281
Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a001834
pubmed: 20182622
Int J Mol Sci. 2015 Aug 13;16(8):19009-26
pubmed: 26287164
Alcohol Clin Exp Res. 2017 Sep;41(9):1551-1558
pubmed: 28722160
Alcohol Clin Exp Res. 2018 Jun 5;:
pubmed: 29870072
Sci Signal. 2010 Apr 06;3(116):ra26
pubmed: 20371769
Pediatrics. 2015 Feb;135(2):264-70
pubmed: 25583914
Birth Defects Res A Clin Mol Teratol. 2008 Apr;82(4):177-86
pubmed: 18240165
Methods Mol Biol. 2009;519:339-50
pubmed: 19381593
Development. 2014 Mar;141(6):1404-15
pubmed: 24595293
PLoS One. 2016 Nov 9;11(11):e0165081
pubmed: 27828986
Science. 2016 Jan 22;351(6271):379-84
pubmed: 26798014
Alcohol Clin Exp Res. 1990 Oct;14(5):650-5
pubmed: 2264592
Ann Neurol. 2012 Dec;72(6):952-60
pubmed: 23280843
Diabetes. 1999 Nov;48(11):2229-39
pubmed: 10535459
Acta Neuropathol Commun. 2017 Jun 6;5(1):44
pubmed: 28587682
Alcohol Clin Exp Res. 2012 Sep;36(9):1519-29
pubmed: 22530671
J Pharmacol Exp Ther. 2010 Jul;334(1):191-8
pubmed: 20308329
Front Integr Neurosci. 2016 Jan 11;9:65
pubmed: 26793073
Cell Mol Life Sci. 2020 May;77(10):1959-1986
pubmed: 31392351
Mol Hum Reprod. 2016 Feb;22(2):130-42
pubmed: 26646502
Reprod Toxicol. 2012 Dec;34(4):538-44
pubmed: 22960358
Alcohol Clin Exp Res. 2002 Aug;26(8 Suppl):44S-48S
pubmed: 12198374
Alcohol Clin Exp Res. 1990 Oct;14(5):662-9
pubmed: 2264594
Drug Alcohol Depend. 1984 Sep;14(1):1-10
pubmed: 6386408
Thromb Haemost. 2004 Jun;91(6):1129-36
pubmed: 15175799
J Pediatr. 1980 Jun;96(6):978-82
pubmed: 7373484
Alcohol. 2010 Nov-Dec;44(7-8):673-90
pubmed: 20053520
J Biol Chem. 2004 Apr 30;279(18):19230-8
pubmed: 14985356
Am J Pathol. 1994 Sep;145(3):640-9
pubmed: 8080046
J Clin Invest. 1992 Jan;89(1):244-53
pubmed: 1729274
Nat Commun. 2013;4:2149
pubmed: 23857367
Cell Mol Life Sci. 2014 May;71(10):1881-92
pubmed: 24287896
Neuron. 2010 Apr 29;66(2):205-19
pubmed: 20434998
J Neurochem. 1990 Jan;54(1):62-71
pubmed: 2136706
Alcohol Clin Exp Res. 2001 Jun;25(6 Suppl):55S-8S
pubmed: 11410743
Clin Chim Acta. 1959 Nov;4:784-7
pubmed: 14418939
Alcohol Clin Exp Res. 2014 May;38(5):1390-400
pubmed: 24588274
Biochim Biophys Acta. 2002 Dec 12;1588(3):217-25
pubmed: 12393176
Gene Expr Patterns. 2006 Jun;6(5):495-503
pubmed: 16455310