Fetal nuchal edema and developmental anomalies caused by gene mutations in mice

Abstract

Fetal nuchal edema, a subcutaneous accumulation of extracellular fluid in the fetal neck, is detected as increased nuchal translucency (NT) by ultrasonography in the first trimester of pregnancy. It has been demonstrated that increased NT is associated with chromosomal anomalies and genetic syndromes accompanied with fetal malformations such as defective lymphatic vascular development, cardiac anomalies, anemia, and a wide range of other fetal anomalies. However, in many clinical cases of increased NT, causative genes, pathogenesis and prognosis have not been elucidated in humans. On the other hand, a large number of gene mutations have been reported to induce fetal nuchal edema in mouse models. Here, we review the relationship between the gene mutants causing fetal nuchal edema with defective lymphatic vascular development, cardiac anomalies, anemia and blood vascular endothelial barrier anomalies in mice. Moreover, we discuss how studies using gene mutant mouse models will be useful in developing diagnostic method and predicting prognosis.

Maternal sterol 27-hydroxylase is crucial for securing fetal development

“…However, a few E16.5 Cyp27a1 KO mat fetuses exhibited bleeding from the deep neck, and subcutaneous hemorrhage spread diffusely over the body, suggesting the occurrence of the critical events during E14.5-16.5 (Figure 2A). We also noticed that many E16.5 Cyp27a1 KO mat hydropathic fetuses had fetal nuchal edema in their subcutaneous back (Supplementary Figure S3), which is associated with various fetal abnormalities, including defective lymphatic vascular development, cardiac anomalies, and anemia (Sugiyama and Hirashima, 2022). The bleeding phenotype was more evident in the E18.5 embryos than in the E16.5 embryos.…”

“…We also noticed that many E16.5 Cyp27a1 KO mat hydropathic fetuses had fetal nuchal edema in their subcutaneous back (Supplementary Figure S3), which is associated with various fetal abnormalities, including defective lymphatic vascular development, cardiac anomalies, and anemia (Sugiyama and Hirashima, 2022). The bleeding phenotype was more evident in the E18.5 embryos than in the E16.5 embryos.…”