Placental mitochondria have high activity of the enzyme glycerol 3-phosphate dehydrogenase (mGPDH), which feeds into the electron transport system. The specific role of mGPDH in the placenta is unknown, but it is linked to glucose and lipid metabolism and is known to produce high levels of reactive oxygen species (ROS). There is evidence of placental oxidative stress in pregnancy diseases such as preeclampsia, so understanding the role of mGPDH in the placenta is important, particularly early in pregnancy when placental development is critical.
Therefore, we aimed to confirm the activity and ROS production of mGPDH in first trimester placentae relative to other sources of mitochondrial ROS. Additionally, we investigated whether mGPDH is differentially expressed in cytotrophoblast (CTB) and syncytiotrophoblast (STB) mitochondria as they are known to have different morphology and activities.
All experiments were performed on first trimester placentae collected with informed consent. Simultaneous mitochondrial respiration and ROS production rates were measured in high resolution respirometers coupled with fluorimeters, using multiple substrate protocols (n = 7-10). Localisation of mGPDH was determined using immunohistochemistry on paraformaldehyde-fixed paraffin-embedded placental samples (5-12 weeks gestational age, n=5 samples per gestational week).
First trimester placental explants demonstrated an ability to utilise mGPDH to respire and produce ROS as expected. The rate of ROS production by mGPDH was significantly higher than that of complexes I or II. Both STB and CTB stained positively for mGPDH and in 40% of images analysed, we observed more intense staining in CTB than STB. This staining pattern was significantly more frequent in the samples less than 10 weeks of gestational age.
First trimester placental mitochondria have the potential to produce high levels of ROS through mGPDH and it may be more active in CTB than STB in early gestation.