Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Maternal circulating antioxidant function and microRNAs may influence placental gene expression and gestational diabetes pathophysiology (#191)

Hasini Rathnayake 1 , Albert Liang 1 , Richard Lai 1 , Kshiti Patel 1 , Aaron Lorimer 1 , Mariama Kamara 1 , Kerry Richard 2 , Fabricio Da Silva Costa 3 4 , Olivia Holland 1
  1. School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, Queensland, Australia
  2. Conjoint Internal Medicine Laboratory, Pathology Queensland; Department of Endocrinology and Diabetes, Royal Brisbane and Women’s Hospital; School of Biomedical Sciences, Queensland University of Technology; School of Medicine, University of Queensland., Queensland, Australia
  3. Maternal Fetal Medicine Unit, Gold Coast University Hospital, Gold Coast, Queensland, Australia
  4. School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia

Gestational diabetes (GDM) may be controlled with diet, but requires medication if severe; however, what leads to severe GDM in some women but not others is unclear. To investigate placental involvement in GDM, we determined if the placental stress-response is altered in GDM compared to healthy pregnancies and is distinct between mild (diet treated) and severe (medicated) GDM pregnancies. To investigate if related changes can be detected during pregnancy, we profiled maternal circulating antioxidant capacity and microRNA expression.

Placental tissue (≥37 week’s gestation) and maternal plasma (26–28 week’s gestation) was collected from control (uncomplicated), GDM diet treated (GDMD), and GDM medicated (GDMM) pregnancies (n≥8 per group). Groups were matched for delivery mode, maternal age, maternal BMI, and infant weight. Placental expression of 239 genes was measured by qPCR. Antioxidant capacity was measured by activity assay. Maternal circulating expression of 800 microRNAs was measured using the nCounter system.

Twenty placental genes had potentially biologically meaningful changes, eight genes down-regulated and four genes up-regulated in GDM compared to control. Eight genes were up-regulated in GDMD but down-regulated in GDMM. Placental antioxidant capacity was decreased in male GDMD and female GDMM, and increased in female GDMD, relative to controls. Circulating antioxidant capacity was reduced in GDMM compared to GDMD and controls. Circulating expression of 16 microRNAs was different between GDM and controls. Nine microRNAs were upregulated in GDMD, and five in GDMM, compared to controls.

The placenta may not be adapting successfully in severe GDM, with lower expression of genes involved in antioxidants, metabolism, and drug processing in GDMM placentae, suggesting a dampened response to stimuli. This gene level response may relate to lowered antioxidant capacity in GDM in both placental and maternal compartments. Circulating antioxidant capacity and microRNA profiles may be effective in distinguishing which women are likely to require medication.