Poster Presentation ESA-SRB 2023 in conjunction with ENSA

Placental gene function and maternal circulating microRNA levels related to gestational diabetes mellitus severity (#382)

Hasini Rathnayake 1 , Mariama Kamara 1 , Fabricio Da Silva Costa 2 3 , Avinash Kundar 1 , Indu Singh 1 , Olivia Holland 1
  1. School of Pharmacy and Medical Sciences, Griffith University, Gold Coast , Queensland, Australia
  2. Maternal Fetal Medicine Unit, Gold Coast University Hospital, Gold Coast, Queensland, Australia
  3. School of Medicine and Dentistry, Griffith University, Gold Coast , Queensland, Australia

Gestational diabetes mellitus (GDM) is a common pregnancy complication that affects maternal and perinatal health. Maternal blood glucose levels increase at ~24 gestational weeks as part of normal pregnancy but are increased pathologically in GDM. GDM is initially treated with diet, with medication indicated in more severe cases. GDM pathology and severity may be related to placental stress response, however, it is not known how maternal and placental systems interact in GDM pathophysiology. Gene expression can be downregulated by microRNAs, therefore we investigated whether placental stress response-related gene expression could be related to maternal microRNAs. Gene expression (84 genes of interest related to cell stress) and microRNAs (800 untargeted) were measured in placenta tissue (≥37 gestational weeks) and maternal plasma (24–28 gestational weeks), respectively, from uncomplicated, GDM-diet treated (GDMD), and GDM-medicated (GDMM) pregnancies (n=8/group). MicroRNA gene regulation was predicted via TargetScan. Eight genes (CYP2C19, CYP2C9, HMOX1, ACADSB, FMO4, CAT, CRYAA, HSPD1) were significantly downregulated in GDMM compared to GDMD pregnancies (fold regulation -1.54 to -2.99), and these genes were also upregulated in GDMD, and downregulated in GDMM, compared to uncomplicated pregnancies, respectively. Five microRNAs (miR-126-3P, miR-1322, miR-2117, miR-320C, miR-502-5p) were significantly upregulated in GDMM compared to GDMD pregnancies (fold change 0.59 to 0.73), and three of these microRNAs (miR-2117, miR-1322, miR 502-5p) are predicted to regulate four of the downregulated placental genes (CYP2C19, ACADSB, FMO4, HSPD1). Downregulated genes have roles in fatty acid metabolism (CYP2C19), blood glucose levels (ACADSB), oxidative and xenobiotic metabolism (FMO4), and mitochondrial function (HSPD1). Maternal circulating microRNAs dysregulated at 24–28 gestational weeks may influence placental gene expression and pathophysiology related to GDM severity. Measurement of these microRNAs at the time of GDM diagnosis at ~24 gestational weeks may be useful in risk prediction for medication necessity.