Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Maternal stress, anxiety, and depression are all associated with increased placental glucocorticoid receptor D1 isoform expression in cohorts from Queensland and South Australia. (#192)

Sreeparna SB Bhaumik 1 2 , Jack JL Lockett 1 3 , Vicki VC Clifton 1 2
  1. University of Queensland, Woolloongabba, QLD, Australia
  2. Mater Research Institute, Brisbane
  3. Princess Alexandra Hospital, Metro South Health, Brisbane

Mental health illness affects 15% of pregnancies. It is associated with poor perinatal and fetal outcomes which may be mediated by heightened hypothalamic-pituitary-adrenal (HPA) axis activity and elevated circulating glucocorticoids. The placenta contains thirteen glucocorticoid receptor (GR) protein isoforms that vary with maternal stress or glucocorticoid exposure. This study investigated whether mental health disorders during pregnancy alter the placental GR isoform profile. We hypothesized that stress, anxiety, and depression (SAD) may be exacerbated due to an altered placental response to glucocorticoids mediated by differential expression of placental GR isoforms that activate inflammatory pathways.

 

Using validated questionnaires for assessment of SAD, pregnant women from the Queensland Family Cohort (QFC) and the South Australia Cohort (SAC) were divided into controls (n=33, QFC; n=58, SAC) and a SAD group (n=33, QFC; n=71, SAC). Placental GR isoform expression was measured using Western blot. Glucocorticoid signaling genes were assessed using qPCR. Levels were compared between SAD and control groups with statistical significance considered at p<0.05.

 

GR isoforms identified in the placenta included GRα-A, GR-β, GR-C1-3, GR-P, GR-A, and GRα-D1-3. Nuclear GRα-D1 was significantly higher in women with SAD compared to controls in both cohorts (p=0.023, QFC; p=0.022, SAC). In the QFC, this increase was exclusive to the placentae of female fetuses (p=0.002), while SAC showed no sex differences. In the QFC, pro-inflammatory markers IL-6 (p=0.0006) and TNF-α (p=0.002) were elevated in women with SAD, with IL-6 specifically higher in female placentas (p=0.01). The anti-inflammatory IL-10 gene was reduced in SAD women (p=0.005), seen only in female placentas (p=0.03). Glucocorticoid-related gene expression in the SAC remains to be investigated.

 

In conclusion, mental health disorders during pregnancy are associated with a pro-inflammatory environment along with an upregulation of GRaD1, suggesting a role of this isoform in exacerbating materno-placental inflammation.