Rats with Placental Ischemia and Preeclampsia-like Symptoms Have Increased Circulating Cell-free Mitochondrial DNA




Goulopoulou, Styliani
Gardner, Jennifer
Phillips, Nicole
Davidge, Sandra
Cushen, Spencer
Morton, Jude
Spaans, Floortje
Kirschenman, Raven


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Preeclampsia (PE) is a hypertensive disorder of pregnancy, which is characterized by placental mitochondrial dysfunction. Increased circulating cell-free mitochondrial DNA (mtDNA) has been also reported in PE. Animal models are commonly used to study the role of placental dysfunction in the maternal syndrome of PE. The objective of this study was to determine the concentrations of circulating mtDNA in rat models of placental ischemia. Placental ischemia was induced in rats on gestational day (GD) 14 by placing clips on a) the abdominal aorta and ovarian arteries (reduced uterine perfusion pressure (RUPP)) and b) ovarian arteries and uterine arteries (selective RUPP (sRUPP)). Sham rats had clips placed on intraabdominal fat. Different groups of rats were exposed to hypoxia (11% O2) or maintained at atmospheric conditions (21% O2) from GD6 to GD21. Blood samples were collected on GD21. Real time PCR quantification of mtDNA was performed on DNA extracts from serum using TaqMan™ probes and chemistry. mtDNA copy number (CN) was greater in RUPP and sRUPP rats compared to their respective controls (Sham (11) vs. RUPP (11): 0.18 ± 0.04 CN/μl vs. 0.30 ± 0.04 CN/μl, p-value: 0.04; Sham (8) vs. sRUPP (10): 24.84 ± 3.29 CN/μl vs. 54.38 ± 3.29 CN/μl, p-value: 0.016)). Hypoxia did not affect mtDNA CN (Control (7) vs. Hypoxia (9): 0.28 ± 0.05 CN/μl vs. 0.36 ± 0.04 CN/μl, p-value: 0.28). Rats with placental ischemia have increased circulating cell-free mtDNA similar to what is seen in pregnant women with PE.