Investigating mitochondrial dysfunction and meta-inflammation as a shared pathogenic network in pre-eclampsia and gestational diabetes mellitus

Pre-eclampsia (PE) and gestational diabetes (GDM) are two common complications of pregnancy. PE is characterised by high blood pressure and increased protein in the urine. GDM develops because the mother's body is not able to produce the extra insulin needed for pregnancy. Together, these pregnancy complications affect 15% of first time mothers. There is significant evidence that failure to respond properly to insulin (insulin resistance) is a central cause of both complications. Although PE and GDM recede after birth, both mother and child have an increased risk of developing heart disease and type II diabetes later in life. Strikingly, in the last decade the prevalence of both pregnancy complications has increased in Ireland because women are older and likely to be overweight giving birth. Mitochondria provide us with energy released from our food. Mitochondria are abundant in the placenta to cope with the increased energy demands during pregnancy. However, this process is complex and if it fails, by-products of the energy-generating mitochondrial network can be stressful to our bodies. Obesity can also disrupt the mitochondrial network causing inflammation in our adipose tissue, making it difficult for our bodies to use insulin properly. We have generated data which links mitochondrial dysfunction with pre-eclampsia and GDM. Initially we will measure levels of mitochondrial damage in the mother's blood. We will examine the relationship between the placenta and adipose tissue in PE and GDM to determine the cause of insulin resistance. We will investigate the therapeutic potential of targeting mitochondrial function for treating PE and GDM. My ultimate goal is to 1) identify the disruptive pathways causing PE and GDM and 2) provide an efffective therapy to improve the long-term outcome of pregnancy for both mothers and babies.

Award Date
04 July 2017
Award Value
€793,072
Principal Investigator
Dr Cathal McCarthy
Host Institution
University College Cork
Scheme
Emerging Investigator Awards