Decreased expression of Gcm1 and its downstream targets Syncytin A and B is associated with severity of feto‐placental phenotypes in the BPH/5 model of preeclampsia (PE)

Abstract

BPH/5 mice spontaneously develop the cardinal features of PE during pregnancy, including late gestational hypertension and proteinuria, along with fetoplacental abnormalities. We have utilized ultrasonography to categorize fetoplacental units (FPUs) at e10.5 into three increasingly severe phenotypic classes (I, II, and III). We tested the hypothesis that Gcm1, a key transcription factor in early trophoblast differentiation, and its downstream targets, Syncytin A and B, are dysregulated in BPH/5 FPUs at e10.5, and this is associated with phenotypic severity. Real‐time PCR revealed downregulation of each of these genes in compromised Class II and Class III BPH/5 FPUs vs C57 controls: Gcm1 (II= 0.3±0.16; III= 0.01±0.003 fold vs C57, n=3 p<0.05), Syncytin A (II= 0.6±0.21, III= 0.05±0.008 fold vs C57, n=3 p<0.05), and Syncytin B (II= 0.69±0.02, III= 0.30±0.14 fold vs C57, n=3 p<0.05). In situ hybridization for Gcm1, Syncytin A and B confirmed this and localized downregulation to the developing labyrinth. Finally, Western analysis revealed decreased Gcm1 protein levels in BPH/5 Class I (29.1±14.3%, n=4, p<0.01) and Class II (43.4±5.2%, n=4, p<0.01) placentas vs C57 (n=6). This suggests that dysregulation of Gcm1 and its downstream targets Syncytin A and B may be involved in the abnormal labyrinth formation and fetoplacental demise observed in this model of PE. Funding: QNRF NPRP09‐1099‐279.