TY - JOUR
T1 - Cell-free mitochondrial DNA increases in maternal circulation during healthy pregnancy
T2 - A prospective, longitudinal study
AU - Cushen, Spencer C.
AU - Sprouse, Marc L.
AU - Blessing, Alexandra
AU - Sun, Jie
AU - Jarvis, Sara S.
AU - Okada, Yoshiyuki
AU - Fu, Qi
AU - Romero, Steven A.
AU - Phillips, Nicole R.
AU - Goulopoulou, Styliani
N1 - Funding Information:
This research was supported in part by the American Heart Association Grant Nos. 13SDG17050056 (to S. Goulopoulou), 13GRNT16990064 (to Q. Fu), 18PRE33960162 (to S. C. Cushen), and 19TPA34850131 (to S. Goulo-poulou) and the National Institutes of Health Grant No. HL088184 (to Q. Fu).
Funding Information:
This research was supported in part by the American Heart Association Grant Nos. 13SDG17050056 (to S. Goulopoulou), 13GRNT16990064 (to Q. Fu), 18PRE33960162 (to S. C. Cushen), and 19TPA34850131 (to S. Goulopoulou) and the National Institutes of Health Grant No. HL088184 (to Q. Fu).
Publisher Copyright:
Copyright © 2020 the American Physiological Society
PY - 2020/2
Y1 - 2020/2
N2 - Mitochondrial DNA (mtDNA) exposed to the extracellular space due to cell death has immunostimulatory properties. Case-control studies reported a positive association between odds of developing preeclampsia and circulating mtDNA. These findings are based on relative quantification protocols that do not allow determination of absolute concentrations of mtDNA and are highly sensitive to nuclear DNA contamination. Furthermore, circulating mtDNA concentrations in response to normal pregnancy, which is an inflammatory state characterized by continuous placental cell apoptosis, have not been established. The main objective of this study was to determine longitudinal changes in circulating mtDNA from preconception to first trimester, third trimester, and postpartum in healthy pregnant women. Absolute real-time PCR quantification of mtDNA and nuclear DNA (nDNA) was performed on whole genomic extracts from serum using TaqMan probes and chemistry. Serum cell-free mtDNA and nDNA concentrations were greater in late pregnancy as compared with early pregnancy and postpartum. Pregnant women carrying neonates at the upper quartile of birth length distribution had higher concentrations of mtDNA in late pregnancy compared with pregnancies carrying neonates at the lower quartile. The correlation between circulating mtDNA and nDNA concentrations varied by sex (i.e., pregnancies carrying female vs. male fetuses). This study is the first to establish temporal patterns of circulating cell-free mtDNA concentrations in normal human pregnancy using absolute DNA quantification techniques. Concentrations of circulating mtDNA in normal pregnancy may be used as reference values for the development of clinical prognostic or diagnostic tests in pregnant women with, or at risk of developing, gestational complications.
AB - Mitochondrial DNA (mtDNA) exposed to the extracellular space due to cell death has immunostimulatory properties. Case-control studies reported a positive association between odds of developing preeclampsia and circulating mtDNA. These findings are based on relative quantification protocols that do not allow determination of absolute concentrations of mtDNA and are highly sensitive to nuclear DNA contamination. Furthermore, circulating mtDNA concentrations in response to normal pregnancy, which is an inflammatory state characterized by continuous placental cell apoptosis, have not been established. The main objective of this study was to determine longitudinal changes in circulating mtDNA from preconception to first trimester, third trimester, and postpartum in healthy pregnant women. Absolute real-time PCR quantification of mtDNA and nuclear DNA (nDNA) was performed on whole genomic extracts from serum using TaqMan probes and chemistry. Serum cell-free mtDNA and nDNA concentrations were greater in late pregnancy as compared with early pregnancy and postpartum. Pregnant women carrying neonates at the upper quartile of birth length distribution had higher concentrations of mtDNA in late pregnancy compared with pregnancies carrying neonates at the lower quartile. The correlation between circulating mtDNA and nDNA concentrations varied by sex (i.e., pregnancies carrying female vs. male fetuses). This study is the first to establish temporal patterns of circulating cell-free mtDNA concentrations in normal human pregnancy using absolute DNA quantification techniques. Concentrations of circulating mtDNA in normal pregnancy may be used as reference values for the development of clinical prognostic or diagnostic tests in pregnant women with, or at risk of developing, gestational complications.
KW - Cell-free DNA
KW - DNA quantification
KW - Gestational age
KW - Mitochondria
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U2 - 10.1152/AJPREGU.00324.2019
DO - 10.1152/AJPREGU.00324.2019
M3 - Article
C2 - 31913687
AN - SCOPUS:85078870759
SN - 0363-6119
VL - 318
SP - R445-R452
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
IS - 2
ER -