Oral Presentation ESA-SRB 2023 in conjunction with ENSA

The role of mitochondria in programming placental and fetal growth (#4)

Joshua Fisher 1
  1. Hunter Medical Research Institute, School of Medicine and Public Health, College of Health, Medicine and Wellbeing, The University of Newcastle, NSW, Australia

Fetal growth restriction (FGR) affects approximately 10% of births in Australia each year, a statistic which equates to approximately 21,000 babies. FGR is defined as the inability of a fetus to reach its predetermined growth potential. Critically FGR directly contributes to ~5% of perinatal deaths in Australia. However, the mechanisms that underpin FGR remain elusive, with lifestyle, genetic, and maternal factors contributing to a broad range of insults collectively termed placental insufficiencies. Our recent work has established that mitochondria are essential for optimal placental function and appear dysregulated in FGR. We suggest this results in a lack the bioenergetic capacity to facilitate growth and development of the placenta and fetus. Our subsequent analysis established that single nucleotide polymorphisms within the nuclear genome present in gene regions that encode mitochondrial structure are correlated with decreased birthweight. A finding conserved in FGR placenta (n=15) at the gene and protein level. These findings have led us to develop a methodology of in-situ imaging of mitochondrial reticular networks, volume, and structure via cyro-electron microscopy. A technique which allows focus ion beam milling and imaging of placental sections 200nm in thickness, and the production of 3-dimensional reconstructions of placental villi using micro-CT and Serial block-face scanning electron microscopy. These projects have established the presence of mitochondrial dysfunction within the placenta of FGR, identified a potential mechanism of pathogenesis, and developed an innovative way to examine mitochondria within the placenta.