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PLGF, a placental marker of fetal brain defects after in utero alcohol exposure
Matthieu Lecuyer1, Annie Laquerrière1,2, Soumeya Bekri1,3
1UNIROUEN, Inserm U1245 and Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Normandie University, Rouen, France.
Insights
Prenatal alcohol exposure damages placental blood vessel development, reducing key growth factors. This placental damage leads to fetal brain vascular defects, potentially aiding early diagnosis of fetal alcohol spectrum disorders (FASD).
Area of Science:
- Neuroscience
- Developmental Biology
- Obstetrics
Background:
- Fetal Alcohol Spectrum Disorders (FASD) present a diagnostic challenge, as not all children exhibit full Fetal Alcohol Syndrome (FAS) features.
- Proper brain development relies on accurate angiogenesis, a process sensitive to prenatal alcohol exposure.
- The placenta, a source of angiogenic factors, is implicated in alcohol-induced fetal brain vascular defects.
Purpose of the Study:
- To investigate the placenta's role in alcohol-induced fetal brain vascular defects.
- To determine if placental growth factor (PlGF) mediates alcohol's effects on fetal brain angiogenesis.
- To explore the potential of PlGF as a biomarker for early FASD diagnosis.
Main Methods:
- In mice: in vivo repression and overexpression of placental growth factor (PlGF) to assess its role in fetal brain angiogenesis.
- In humans: comparative molecular and morphological analysis of brain and placental angiogenesis in alcohol-exposed fetuses.
- Assessed PlGF levels and vascular morphology in placental and brain tissues.
Main Results:
- Prenatal alcohol exposure impaired placental angiogenesis and reduced PlGF levels, leading to altered fetal brain vasculature.
- Placental PlGF repression mimicked alcohol-induced brain vascular defects; PlGF overexpression rescued these effects in mice.
- Human alcohol-exposed fetuses showed disrupted placental and brain angiogenesis, with decreased PlGF correlating to placental vascular impairments.
Conclusions:
- Placental PlGF disruption is a key mechanism in alcohol-induced fetal brain angiogenesis defects.
- Impaired placental angiogenesis and reduced PlGF likely predict brain disabilities in infants exposed to alcohol in utero.
- Measuring placental PlGF at birth may aid in the early diagnosis of FASD.
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.
