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Acta Neuropathol Commun. 2017 Jun 6;5(1):44. doi: 10.1186/s40478-017-0444-6.

PLGF, a placental marker of fetal brain defects after in utero alcohol exposure.

Author information

1
UNIROUEN, Inserm U1245 and Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Normandie University, Rouen, France.
2
Department of Pathology, Rouen University Hospital, Rouen, France.
3
Department of Molecular Biochemistry, Rouen University Hospital, Rouen, France.
4
Department of Pathology, Brest University Hospital, Rouen, France.
5
Department of Neonatal Paediatrics and Intensive Care, Rouen University Hospital, Rouen, France.
6
UNIROUEN, Inserm U1245 and Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Normandie University, Rouen, France. bruno.gonzales@univ-rouen.fr.

Abstract

Most children with in utero alcohol exposure do not exhibit all features of fetal alcohol syndrome (FAS), and a challenge for clinicians is to make an early diagnosis of fetal alcohol spectrum disorders (FASD) to avoid lost opportunities for care. In brain, correct neurodevelopment requires proper angiogenesis. Since alcohol alters brain angiogenesis and the placenta is a major source of angiogenic factors, we hypothesized that it is involved in alcohol-induced brain vascular defects. In mouse, using in vivo repression and overexpression of PLGF, we investigated the contribution of placenta on fetal brain angiogenesis. In human, we performed a comparative molecular and morphological analysis of brain/placenta angiogenesis in alcohol-exposed fetuses. Results showed that prenatal alcohol exposure impairs placental angiogenesis, reduces PLGF levels and consequently alters fetal brain vasculature. Placental repression of PLGF altered brain VEGF-R1 expression and mimicked alcohol-induced vascular defects in the cortex. Over-expression of placental PGF rescued alcohol effects on fetal brain vessels. In human, alcohol exposure disrupted both placental and brain angiogenesis. PLGF expression was strongly decreased and angiogenesis defects observed in the fetal brain markedly correlated with placental vascular impairments. Placental PGF disruption impairs brain angiogenesis and likely predicts brain disabilities after in utero alcohol exposure. PLGF assay at birth could contribute to the early diagnosis of FASD.

KEYWORDS:

Angiogenesis; Cortex; Fetal alcohol exposure; Placenta

PMID:
28587682
PMCID:
PMC5461764
DOI:
10.1186/s40478-017-0444-6
[Indexed for MEDLINE]
Free PMC Article

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