Mitochondrial heterogeneity in a patient with preeclampsia

Preeclampsia (PE) is a pregnancy disorder characterized by high blood pressure and proteinuria after the 20th week. In this condition, reduced blood flow to the placenta leads to placental ischemia and oxidative stress, resulting in mitochondrial DNA damage and dysfunction. In this case of preeclampsia, a unique feature is observed: the presence of mitochondrial heterogeneity and heteroplasmy in the preeclamptic placenta, but not in circulating plasma. We found a single nucleotide addition (m.310C) in the MT-D-loop region and a heteroplasmic mutation (m.7681C < T) in the Cytochrome C Oxidase Subunit II (MT-COX2) gene. This heteroplasmic mutation causes a phenylalanine (F) to serine (S) substitution in the MT-COX2 protein. A cost-effective Tetra ARMS PCR assay was developed to screen this heteroplasmic variation, producing distinctive 269-bp, 197-bp (T), and 132-bp (C) bands. Additionally, mitochondrial mutational burden measurement in placental tissue indicated a higher number of mutant mitochondria than in WT, suggesting a significant mutational burden. Ultrastructural examination of the patient's placenta via electron microscopy demonstrated a mix of healthy oval mitochondria alongside stressed (rounded mitochondria) and increased vacuolization and collagen fibril formation. These findings suggest that mtDNA mutations that may play a role in altered mitochondrial morphology may contribute to mitochondrial dysfunction in the patient's placental pathology, which needs to be further investigated.