Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Neuronal molecule, NrCAM, is highly dysregulated in pregnancies complicated by fetal growth restriction. (#457)

Lucy Bartho 1 2 , Susan P Walker 1 2 , Alexander Heazell 3 4 , Amanda Sferruzzi-Perri 5 , Ping Cannon 1 2 , Tuong-Vi Nguyen 1 2 , Anna Nguyen 1 2 , Georgia Wong 1 2 , Natalie J Hannan 1 2 , Stephen Tong 1 2 , Tu'uhevaha J Kaitu'u-Lino 1 2
  1. Department of Obstetrics and Gynaecology, University of Melbourne and Mercy Hospital for Women, Melbourne, Victoria, Australia
  2. University of Melbourne, Heidelberg, VIC, Australia
  3. Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
  4. Saint Mary’s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
  5. Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Neuronal cell adhesion molecule (NrCAM), a member of the superglobulin family, is highly expressed in the nervous system, and placenta. This study aimed to characterise NrCAM in plasma and placenta of women who delivered fetal growth restricted (FGR, birthweight <3rd centile) infants.

Circulating plasma NrCAM was reduced in women who delivered preterm (<34 weeks’ gestation) with FGR (n=23), compared to controls (n=20, p=0.0003, AUC=0.82). In women with reduced fetal movements (RFM, high risk for stillbirth), circulating NrCAM was reduced in those who delivered with FGR (p=0.008, n=12, AUC=0.63), compared to controls (n=235). In a case-cohort collected at 36 weeks’ gestation, circulating NrCAM was significantly reduced in women who later delivered with FGR (n= 27, p<0.0001, AUC=0.77), compared to controls (n=209). Thus, we show that reduced plasma NrCAM is associated with FGR in three separate cohorts.

Next, we measured NrCAM in the placenta, placental cell types, and models of placental insufficiency. NrCAM was reduced in placental lysates from patients who delivered FGR (n=43) <34 weeks’ gestation, compared to preterm controls (p=0.005, n=19). Human trophoblast stem cells (hTSCs) (differentiated into syncytiotrophoblast or extravillous trophoblast cells) or primary trophoblast cells were exposed to hypoxia (1% Oxygen vs 8% Oxygen). NrCAM1 expression was reduced following differentiation of hTSCs into syncytiotrophoblast (p<0.01, n=5), and extravillous trophoblast (p<0.05, n=5) cells. Exposure to hypoxia reduced NrCAM1 expression in cytotrophoblast hTSCs (p=0.008, n=5) and primary trophoblast cells (n=6, p<0.0001). Finally, we measured NrCAM1 in placentas from a mouse model of hypoxia-induced FGR. NrCAM1 was significantly reduced in hypoxic placentas (n=9, p=0.006), compared to normoxia controls (n=9).

NrCAM was highly dysregulated in the circulation of women delivering FGR infants before and after diagnosis. We demonstrated the reduced NrCAM in the placenta is induced by hypoxia, a key characteristic of FGR.