Gestational diabetes (GDM) poses an immediate threat to thousands of pregnancies, and affects the ongoing health of mothers and babies. GDM may be controlled with diet, but requires medication if symptoms are severe; however, what leads to severe GDM in some at risk women but not others is unclear. The placenta is critical to maternal insulin resistance, and placental response to stress may have a role in GDM.
Aim: Determine if placental expression of stress-response related genes is altered in GDM compared to healthy pregnancies, and is distinct between mild (diet treated) and severe (medication treated) GDM pregnancies.
Placentae were collected from control (no complications), GDM diet treated (GDMD), and GDM medication treated (GDMM) pregnancies. Groups were matched for delivery mode, maternal age, maternal BMI, infant sex (male infants), and infant weight. Expression of 239 genes was measured by qPCR. Fold regulation of ±1.5 with a p-value (t-test) of ≤0.05 in any comparison (control vs. GDMD, control vs. GDMM, GDMD vs. GDMM) was considered potentially biologically meaningful.
Twenty genes had potentially biologically meaningful changes. Eight genes (HSPA12A, DNAJB6, DNAJB5, GPX1, CYP4B1, GPX2, CYP2F1, XDH) were down-regulated and four genes (PTGS2, PRDX6, DUSP1, VIMP) were up-regulated in GDM compared to control. Eight genes (CYP2C19, CYP2C9, HMOX1, ACADSB, FMO4, CAT, CRYAA, HSPD1) were up-regulated in GDMD but down-regulated in GDMM.
Genes altered in placentae from GDM compared to control pregnancies may have roles in GDM aetiology and pathophysiology. Genes with different expression between GDM groups (GDMD vs. GDMM) may represent a response to medication in the GDMM group. Alternatively, cellular stress may lead to an increased gene expression response to maintain cellular homeostasis in less severe GDMD that is not present in the more severe GDMM. Therefore, gene changes may represent a more successful adaptation to stress in GDMD compared to GDMM.