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

ALOX15 expression is elevated in the first trimester placenta and downregulated in term cytotrophoblast under hypoxia (#460)

Natasha de Alwis 1 , Natalie K Binder 1 , Sally Beard 1 , Lydia Baird 1 , Tu'uhevaha J Kaitu'u-Lino 2 , Stephen Tong 2 , Lisa Hui 3 4 , Natalie J Hannan 1
  1. Department of Obstetrics, Gynaecology & Newborn Health, Therapeutics Discovery and Vascular Function in Pregnancy Group, The University of Melbourne, Melbourne, Victoria, Australia
  2. Department of Obstetrics, Gynaecology & Newborn Health, Translational Obstetrics Group, The University of Melbourne, Melbourne, Victoria, Australia
  3. Department of Obstetrics, Gynaecology & Newborn Health, The University of Melbourne, Melbourne, Victoria, Australia
  4. Northern Health, Epping, Melbourne, Victoria, Australia

Preeclampsia and fetal growth restriction (FGR) are serious obstetric complications responsible for significant perinatal mortality and lifelong disability. Previously, we demonstrated that transcripts for gene arachidonate 15-lipoxygenase (ALOX15) were decreased in the circulation of patients with preterm FGR, with and without preeclampsia [1]. As both FGR and preeclampsia feature a dysfunctional placenta, here we investigate whether ALOX15 is altered in the pathological placenta and in key developmental stages across gestation.

ALOX15 expression (qPCR) and protein levels (western blotting) were assessed in placental tissue from cases of preterm (<34 weeks) preeclampsia (n=49), FGR (n=14) and preterm controls (n=10). ALOX15 expression was measured across gestation, in placental tissue collected from first trimester surgical terminations (7-11 weeks; n=11), early preterm (24-30 weeks; n=9), and term caesarean deliveries (38-39 weeks; n=11). Term placental explant tissue and primary cytotrophoblasts were cultured under hypoxic (1% O2) conditions (modelling placental dysfunction) and physiological normoxic (8% O2) conditions, and ALOX15 expression assessed.

ALOX15 expression and protein levels were unaltered in placenta in cases of preeclampsia or FGR compared to preterm controls. ALOX15 expression was expressed in placenta across gestation, with expression highest in the first trimester compared to preterm and term gestations. ALOX15 expression was not detectable in our cultured placental explant tissue under either oxygen condition, but was expressed in isolated pure primary cytotrophoblast populations, with expression reduced under hypoxia.

These data demonstrate that placental ALOX15 does not mirror circulating transcripts, thus it is unlikely the placenta is the major contributor to the reduced circulating transcripts observed in patients with FGR and preeclampsia. However, ALOX15 placental expression is higher in the first trimester, suggesting a potential role in early placental development. Localisation of placental ALOX15 is underway to determine potential temporal and spatial actions in placenta and mechanisms driving placental development.

  1. Hannan NJ, Stock O, Spencer R, Whitehead C, David AL, Groom K, Petersen S, Henry A, Said JM, Seeho S, Kane SC, Gordon L, Beard S, Chindera K, Karegodar S, Hiscock R, Pritchard N, Kaitu’u-Lino TuJ, Walker SP and Tong S. Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth. BMC Medicine. 2020;18:145.