3 minute lightning oral presentation (and poster) ESA-SRB-APEG-NZSE 2022

Paternal Expressed Gene 10 (PEG10) is decreased in preeclampsia (#102)

Lydia Baird 1 2 , Lucy Bartho 1 2 , Fiona Brownfoot 1 2 , Elif Kadife 1 2 , Ping Cannon 1 2 , Manju Kandel 1 2 , Tuong-Vi Nguyen 1 2 , Stephen Tong 1 2 , Tu’uhevaha J Kaitu’u-Lino 1 2
  1. The Department of Obstetrics and Gynaecology, , The University of Melbourne, Melbourne, Victoria, Australia
  2. Mercy Perinatal, Mercy Hospital for Women, Melbourne, Victoria, Australia

Preeclampsia is a serious pregnancy complication that is attributed to placental dysfunction. Trophoblast Paternal Expressed Gene 10 (PEG10) is crucial for normal placental development, with knockout mice demonstrating impaired vascular development1. This study aimed to characterise PEG10 in preeclampsia and human cytotrophoblast stem cells (hTSCs). 

PEG10 messenger RNA (mRNA) expression was significantly reduced in placenta samples from patients with early-onset (<34 weeks’ gestation) preeclampsia (p=0.04, n=78 vs n=18 controls). Immunohistochemistry staining localised PEG10 to the cytotrophoblast layer within the placental villi. Semi-quantitative, blinded assessment of this staining (n=5) confirmed reduced PEG10 protein in preeclamptic placentas (p=0.03, n=5 vs n=5 controls).  PEG10 mRNA and protein are not secreted into the maternal circulation and cannot be used as a diagnostic biomarker.

To confirm PEG10 is enriched in cytotrophoblasts, hTSCs were terminally differentiated into syncytiotrophoblast and extravillous trophoblast (EVT) cells. Differentiation was confirmed by a reduction in cytotrophoblast markers (TEAD4, CDH2) and increase in syncytiotrophoblast (SDC1) and EVT markers (HLAG). PEG10 expression was significantly decreased in syncytiotrophoblast (p<0.0001, n=5 vs n=5 controls) and EVT cells (p<0.001, n=5 vs n=5 controls).

Preeclampsia is associated with excessive placental hypoxia and inflammation, therefore we measured PEG10 mRNA expression when hTSCs were exposed to these conditions. PEG10 was significantly reduced when exposed to hypoxia (1% O2) (p<0.01, n=5 vs n=5 controls). PEG10 expression was also reduced in hTSCs treated with inflammatory cytokine tumour necrosis factor alpha (TNFα) (p<0.01, n=5 vs n=5 controls) but not with interleukin-6 (ns, n=5 vs n=5 controls).

This study demonstrated that PEG10 expression is reduced in placentas from women with early-onset preeclampsia. Although PEG10 is not secreted into the maternal circulation, in vitro studies confirm that TNFα and hypoxia may contribute to reduced placental PEG10 expression. Future studies will elucidate how PEG10 knockdown affects cytotrophoblast proliferation, differentiation, and interaction with human endothelial cells.