Perigestational alcohol consumption induces altered early placentation and organogenic embryo growth restriction by disruption of trophoblast angiogenic factors

COLL ,T.A.; CEBRAL E; VENTUREIRA, MR; BARBEITO C; GUALDONI G; PALOMINO WA

REPRODUCTIVE BIOMEDICINE ONLINE

REPRODUCTIVE HEALTHCARE LTD

Lugar: Amsterdam; Año: 2021 vol. 42 p. 481 - 504

1472-6483

Research Question: Maternal alcohol consumption produces fetal retardation and malformations, probably associated with placental defects. Does perigestational alcohol consumption up to organogenesis lead to abnormal placentation and embryo growth restriction by disrupting the vascular endothelial growth factor (VEGF) system in embryo-placental development?Design: Female mice were treated with 10 % ethanol in drinking water prior to and up to day 10 of gestation. Control females received ethanol-free water. After treatment, the trophoblastic tissue, embryo growth, and the angiogenic VEGF pathway were analyzed.Results: Treated females had resorbed and delayed implantation sites with poor ectoplacental cone development. Reduced trophoblastic area-tissue from treated females had abnormal junctional zone (JZ) and diminished labyrinthine vascularization. After treatment, the labyrinth (Lab) had increased chorionic trophoblast proliferation, HIF-1α immunoexpression but reduced apoptosis. The embryo growth was reduced concomitantly with low VEGF immunostaining but high endothelial nitric oxide synthase (eNOS) expression. In JZ and Lab of treated females, gene and protein immunoexpression of VEGF was reduced and the protein expression of FLT-1 increased compared to controls. Increased activation of KDR receptor (phosphorylated KDR) and expression of eNOS were observed in placenta of treated females. However, immunoexpression of metalloproteinase-9 (MMP-9) was reduced in JZ but increased in Lab, compared to controls. Conclusions: These data reveal inadequate expression of VEGF/receptors and angiogenic eNOS and MMP factors related to abnormal early placentation after perigestational alcohol ingestion, providing insight into etiological factors underlying early placentopathy associated with intrauterine growth restriction due to maternal alcohol consumption.