Placenta-specific protein 1 (PLAC1) expression is significantly down-regulated in preeclampsia via a hypoxia-mediated mechanism

Objective Examine a mechanism of PLAC1 regulation and its potential role in preeclampsia (PE). Materials and methods Placental tissue samples and detailed clinical information were obtained through the University of Iowa Maternal Fetal Tissue Bank (IRB# 200910784) from gestational and maternal age-matched control (n = 17) and PE affected pregnancies (n = 12). PLAC1 and PLAC1 promoter-specific expression was measured using quantitative polymerase chain reaction (qPCR) and differences were assessed via the standard Delta Delta Ct method. In addition, the role of hypoxia in PLAC1 transcription was investigated through the exposure of HTR8/SVneo human trophoblast cells to the hypoxia mimic dimethyloxaloylglycine (DMOG). Results PLAC1 expression is seen to be 8.9-fold lower in human placentas affected by preeclampsia in comparison with controls (p < .05). Further, this decrease is paralleled by a significantly lower expression of the P2 or proximal PLAC1 promoter (p < .05). Expression of mediator complex subunit 1 (MED1), a known hypoxia-sensitive transcription coactivator and PLAC1 effector, is significantly correlated with PLAC 1 expression (r(2) = 0.607, p < .001). These data suggest that PLAC1 expression is significantly down-regulated in preeclampsia at least in part via a MED1 hypoxia-mediated mechanism. Conclusions We confirm that PLAC1 transcription is suppressed in the placentae of women affected by preeclampsia. We further demonstrate that this suppression is driven through the P2 or proximal PLAC1 promoter. This demonstration led to the identification of the MED1-TRAP cofactor complex as the hypoxia-sensitive driver.

Automated summary

The study revealed that PLAC1 transcription is suppressed in preeclampsia-affected placentas, with the suppression driven in part through the P2 promoter. Additionally, the MED1-TRAP cofactor complex was identified as a hypoxia-sensitive driver of PLAC1 down-regulation.