The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Rcbtb2 is reduced in preeclamptic placentas and in placental tissue exposed to hypoxia (#134)

Natasha de Alwis 1 , Sally Beard 1 , Natalie K Binder 1 , Tu'uhevaha J Kaitu'u-Lino 1 , Natasha Pritchard 1 , Sue P Walker 1 , Stephen Tong 1 , Natalie J Hannan 1
  1. Department of Obstetrics and Gynaecology, University of Melbourne, Carlton, VIC, Australia

INTRODUCTION: Placental dysfunction is a key contributor in the development of pre-eclampsia and fetal growth restriction. We have recently identified significantly reduced levels of the mRNA transcript encoding RCC1 and BTB domain containing protein 2 (RCBTB2) in the maternal circulation in pregnancies complicated by severe early onset fetal growth restriction (FGR) and pre-eclampsia (PE).

OBJECTIVE: The current study aimed to determine whether RCBTB2 expression was altered in the human placenta from pregnancies complicated by PE and FGR, and with hypoxia.

METHODS: Placental tissue was collected from severe early onset PE (n=49), FGR (n=16) and gestation matched controls (n=47). Isolated primary cytotrophoblasts (n=5) and placental explant tissue (n=3) from normal term placentas were cultured under normoxia (8% oxygen) and hypoxia (1% oxygen) for 24 hours. RCBTB2 expression was assessed by qPCR. Primary cytotrophoblasts were transfected with RCBTB2 silencing RNA (siRNA) (n=3) to silence gene expression (under normoxia and hypoxia for 48 hours). Secretion of anti-angiogenic factor soluble fms-like tyrosine kinase 1 (sFLT-1) was assessed by ELISA and expression of cell growth and apoptosis associated genes (BAX, BCL2, EGFR and IGF2) by qPCR.  

RESULTS: Comparison of RCBTB2 mRNA expression in dysfunctional placental tissue cohorts demonstrated significantly decreased expression in the PE placenta compared to healthy control placentas, but no significant change in the FGR placental tissue. RCBTB2 mRNA expression was significantly reduced under hypoxic conditions in isolated human cytotrophoblast and placental explant tissue.  Interestingly, silencing RCBTB2 did not alter sFLT-1 secretion nor expression of the cell survival associated genes compared to controls.

CONCLUSION: RCBTB2 is reduced in PE placenta and with hypoxic insult ex vivo. Loss of RCBTB2 does not alter sFLT-1 secretion, cell survival/growth or apoptosis genes. Loss of RCBTB2 may provide a new marker of placental insufficiency but whether it has a role in the pathogenesis of disease remains unknown.