Virtual Presentation SRB Virtual Awards 2020

The sex-dependent steroidogenic capacity of the guinea pig placenta in response to prenatal stress (#8)

Gabrielle K Crombie 1 2 , Hannah K Palliser 1 2 , Julia C Shaw 1 2 , Jonathan J Hirst 1 2
  1. Mothers and Babies Research Centre, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
  2. School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia

               Prenatal stress is associated with the development of neurobehavioral disorders such as Attention Deficit Hyperactivity Disorder (ADHD) in childhood, with susceptibility greater in males. The placenta’s role in protection of the fetus, through metabolism of neuroprotective hormones, is particularly important in prenatal stress events. We propose that the production of placental 5α-reductase type-2 (SRD5A2) enzyme, responsible for the synthesis of allopregnanolone (a key promoter of inhibitory pathways in the fetal brain), responds to prenatal stress events in a sex-dependent manner. Furthermore, that production of 11β-hydroxysteroid type-1 (HSD11B1) and type-2 (HSD11B2) enzymes also respond in a sex-dependent manner to prevent excessive levels of cortisol reaching the fetus.  

                Pregnant guinea pig dams were subjected to repeated, mild psychosocial stress (2 hour strobe light exposure, every 5 days) from gestational age (GA)35-65 (term GA70). Male and female guinea pig placentae were collected immediately after stress events or control-handling for real-time polymerase chain reaction (RT-PCR) and gene expression analysis via the Biomark HD system.

                Stress-exposed female placentae displayed an increased capacity for allopregnanolone synthesis, represented by an increase in relative mRNA expression of SRD5A2 (p=0.04). They also displayed a significant decrease in HSD11B1 (p=0.009) and increase in HSD11B2 (p=0.03) relative mRNA expression, representing cortisol inactivation. Stress-exposed male placentae displayed an increase in SRD5A2 at GA40, however this was not sustained throughout gestation. HSD11B1 expression trended toward an increase whilst HSD11B2 expression was unchanged.

                These data highlight how the female placenta responds to maternal stress by reducing exposure of high cortisol levels to the fetus and simultaneously promoting synthesis of neuroprotective hormones. The absence of these changes in male placentae highlights the increased vulnerability of the male fetus to excitotoxic damage, which likely programs the male offspring to be more vulnerable to neurodevelopmental deficits and neurobehavioural disorders later in life.