TY - JOUR
T1 - A mitochondrial regulator protein, MNRR1, is elevated in the maternal blood of women with preeclampsia
AU - Suksai, Manaphat
AU - Romero, Roberto
AU - Bosco, Mariachiara
AU - Gotsch, Francesca
AU - Jung, Eunjung
AU - Chaemsaithong, Piya
AU - Tarca, Adi L.
AU - Gudicha, Dereje W.
AU - Gomez-Lopez, Nardhy
AU - Arenas-Hernandez, Marcia
AU - Meyyazhagan, Arun
AU - Grossman, Lawrence I.
AU - Aras, Siddhesh
AU - Chaiworapongsa, Tinnakorn
N1 - Publisher Copyright:
© This work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.
PY - 2024
Y1 - 2024
N2 - Objective: Preeclampsia, one of the most serious obstetric complications, is a heterogenous disorder resulting from different pathologic processes. However, placental oxidative stress and an anti-angiogenic state play a crucial role. Mitochondria are a major source of cellular reactive oxygen species. Abnormalities in mitochondrial structures, proteins, and functions have been observed in the placentae of patients with preeclampsia, thus mitochondrial dysfunction has been implicated in the mechanism of the disease. Mitochondrial nuclear retrograde regulator 1 (MNRR1) is a newly characterized bi-organellar protein with pleiotropic functions. In the mitochondria, this protein regulates cytochrome c oxidase activity and reactive oxygen species production, whereas in the nucleus, it regulates the transcription of a number of genes including response to tissue hypoxia and inflammatory signals. Since MNRR1 expression changes in response to hypoxia and to an inflammatory signal, MNRR1 could be a part of mitochondrial dysfunction and involved in the pathologic process of preeclampsia. This study aimed to determine whether the plasma MNRR1 concentration of women with preeclampsia differed from that of normal pregnant women. Methods: This retrospective case–control study included 97 women with preeclampsia, stratified by gestational age at delivery into early (<34 weeks, n = 40) and late (≥34 weeks, n = 57) preeclampsia and by the presence or absence of placental lesions consistent with maternal vascular malperfusion (MVM), the histologic counterpart of an anti-angiogenic state. Women with an uncomplicated pregnancy at various gestational ages who delivered at term served as controls (n = 80) and were further stratified into early (n = 25) and late (n = 55) controls according to gestational age at venipuncture. Maternal plasma MNRR1 concentrations were determined by an enzyme-linked immunosorbent assay. Results: 1) Women with preeclampsia at the time of diagnosis (either early or late disease) had a significantly higher median (interquartile range, IQR) plasma MNRR1 concentration than the controls [early preeclampsia: 1632 (924–2926) pg/mL vs. 630 (448–4002) pg/mL, p =.026, and late preeclampsia: 1833 (1441–5534) pg/mL vs. 910 (526–6178) pg/mL, p =.021]. Among women with early preeclampsia, those with MVM lesions in the placenta had the highest median (IQR) plasma MNRR1 concentration among the three groups [with MVM: 2066 (1070–3188) pg/mL vs. without MVM: 888 (812–1781) pg/mL, p =.03; and with MVM vs. control: 630 (448–4002) pg/mL, p =.04]. There was no significant difference in the median plasma MNRR1 concentration between women with early preeclampsia without MVM lesions and those with an uncomplicated pregnancy (p =.3). By contrast, women with late preeclampsia, regardless of MVM lesions, had a significantly higher median (IQR) plasma MNRR1 concentration than women in the control group [with MVM: 1609 (1392–3135) pg/mL vs. control: 910 (526–6178), p =.045; and without MVM: 2023 (1578–8936) pg/mL vs. control, p =.01]. Conclusions: MNRR1, a mitochondrial regulator protein, is elevated in the maternal plasma of women with preeclampsia (both early and late) at the time of diagnosis. These findings may reflect some degree of mitochondrial dysfunction, intravascular inflammation, or other unknown pathologic processes that characterize this obstetrical syndrome.
AB - Objective: Preeclampsia, one of the most serious obstetric complications, is a heterogenous disorder resulting from different pathologic processes. However, placental oxidative stress and an anti-angiogenic state play a crucial role. Mitochondria are a major source of cellular reactive oxygen species. Abnormalities in mitochondrial structures, proteins, and functions have been observed in the placentae of patients with preeclampsia, thus mitochondrial dysfunction has been implicated in the mechanism of the disease. Mitochondrial nuclear retrograde regulator 1 (MNRR1) is a newly characterized bi-organellar protein with pleiotropic functions. In the mitochondria, this protein regulates cytochrome c oxidase activity and reactive oxygen species production, whereas in the nucleus, it regulates the transcription of a number of genes including response to tissue hypoxia and inflammatory signals. Since MNRR1 expression changes in response to hypoxia and to an inflammatory signal, MNRR1 could be a part of mitochondrial dysfunction and involved in the pathologic process of preeclampsia. This study aimed to determine whether the plasma MNRR1 concentration of women with preeclampsia differed from that of normal pregnant women. Methods: This retrospective case–control study included 97 women with preeclampsia, stratified by gestational age at delivery into early (<34 weeks, n = 40) and late (≥34 weeks, n = 57) preeclampsia and by the presence or absence of placental lesions consistent with maternal vascular malperfusion (MVM), the histologic counterpart of an anti-angiogenic state. Women with an uncomplicated pregnancy at various gestational ages who delivered at term served as controls (n = 80) and were further stratified into early (n = 25) and late (n = 55) controls according to gestational age at venipuncture. Maternal plasma MNRR1 concentrations were determined by an enzyme-linked immunosorbent assay. Results: 1) Women with preeclampsia at the time of diagnosis (either early or late disease) had a significantly higher median (interquartile range, IQR) plasma MNRR1 concentration than the controls [early preeclampsia: 1632 (924–2926) pg/mL vs. 630 (448–4002) pg/mL, p =.026, and late preeclampsia: 1833 (1441–5534) pg/mL vs. 910 (526–6178) pg/mL, p =.021]. Among women with early preeclampsia, those with MVM lesions in the placenta had the highest median (IQR) plasma MNRR1 concentration among the three groups [with MVM: 2066 (1070–3188) pg/mL vs. without MVM: 888 (812–1781) pg/mL, p =.03; and with MVM vs. control: 630 (448–4002) pg/mL, p =.04]. There was no significant difference in the median plasma MNRR1 concentration between women with early preeclampsia without MVM lesions and those with an uncomplicated pregnancy (p =.3). By contrast, women with late preeclampsia, regardless of MVM lesions, had a significantly higher median (IQR) plasma MNRR1 concentration than women in the control group [with MVM: 1609 (1392–3135) pg/mL vs. control: 910 (526–6178), p =.045; and without MVM: 2023 (1578–8936) pg/mL vs. control, p =.01]. Conclusions: MNRR1, a mitochondrial regulator protein, is elevated in the maternal plasma of women with preeclampsia (both early and late) at the time of diagnosis. These findings may reflect some degree of mitochondrial dysfunction, intravascular inflammation, or other unknown pathologic processes that characterize this obstetrical syndrome.
KW - CHCHD2
KW - early preeclampsia
KW - intravascular inflammation
KW - late preeclampsia
KW - maternal vascular malperfusion
KW - oxidative stress
KW - placenta
KW - pregnancy
UR - http://www.scopus.com/inward/record.url?scp=85182398764&partnerID=8YFLogxK
U2 - 10.1080/14767058.2023.2297158
DO - 10.1080/14767058.2023.2297158
M3 - Article
C2 - 38220225
AN - SCOPUS:85182398764
SN - 1476-7058
VL - 37
JO - Journal of Maternal-Fetal and Neonatal Medicine
JF - Journal of Maternal-Fetal and Neonatal Medicine
IS - 1
M1 - 2297158
ER -