TY - JOUR
T1 - Placental Mitochondrial Abnormalities in Preeclampsia
AU - Vangrieken, P.
AU - Al-Nasiry, S.
AU - Bast, A.
AU - Leermakers, P.A.
AU - Tulen, C.B.M.
AU - Schiffers, P.M.H.
AU - van Schooten, F.J.
AU - Remels, A.H.V.
N1 - Funding Information:
This study was supported by the NUTRIM Graduate Program. There was no additional external funding received for this study.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/8
Y1 - 2021/8
N2 - Preeclampsia complicates 5-8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress and mitochondrial abnormalities are considered to play a key role. Mitochondrial abnormalities in preeclamptic placentae have been described, but the extent to which mitochondrial content and the molecular pathways controlling this (mitochondrial biogenesis and mitophagy) are affected in preeclamptic placentae is unknown. Therefore, in preeclamptic (n = 12) and control (n = 11) placentae, we comprehensively assessed multiple indices of placental antioxidant status, mitochondrial content, mitochondrial biogenesis, mitophagy, and mitochondrial fusion and fission. In addition, we also explored gene expression profiles related to inflammation and apoptosis. Preeclamptic placentae were characterized by higher levels of oxidized glutathione, a higher total antioxidant capacity, and higher mRNA levels of the mitochondrial-located antioxidant enzyme manganese-dependent superoxide dismutase 2 compared to controls. Furthermore, mitochondrial content was significantly lower in preeclamptic placentae, which was accompanied by an increased abundance of key constituents of glycolysis. Moreover, mRNA and protein levels of key molecules involved in the regulation of mitochondrial biogenesis were lower in preeclamptic placentae, while the abundance of constituents of the mitophagy, autophagy, and mitochondrial fission machinery was higher compared to controls. In addition, we found evidence for activation of apoptosis and inflammation in preeclamptic placentae. This study is the first to comprehensively demonstrate abnormalities at the level of the mitochondrion and the molecular pathways controlling mitochondrial content/function in preeclamptic placentae. These aberrations may well contribute to the pathophysiology of preeclampsia by upregulating placental inflammation, oxidative stress, and apoptosis.
AB - Preeclampsia complicates 5-8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress and mitochondrial abnormalities are considered to play a key role. Mitochondrial abnormalities in preeclamptic placentae have been described, but the extent to which mitochondrial content and the molecular pathways controlling this (mitochondrial biogenesis and mitophagy) are affected in preeclamptic placentae is unknown. Therefore, in preeclamptic (n = 12) and control (n = 11) placentae, we comprehensively assessed multiple indices of placental antioxidant status, mitochondrial content, mitochondrial biogenesis, mitophagy, and mitochondrial fusion and fission. In addition, we also explored gene expression profiles related to inflammation and apoptosis. Preeclamptic placentae were characterized by higher levels of oxidized glutathione, a higher total antioxidant capacity, and higher mRNA levels of the mitochondrial-located antioxidant enzyme manganese-dependent superoxide dismutase 2 compared to controls. Furthermore, mitochondrial content was significantly lower in preeclamptic placentae, which was accompanied by an increased abundance of key constituents of glycolysis. Moreover, mRNA and protein levels of key molecules involved in the regulation of mitochondrial biogenesis were lower in preeclamptic placentae, while the abundance of constituents of the mitophagy, autophagy, and mitochondrial fission machinery was higher compared to controls. In addition, we found evidence for activation of apoptosis and inflammation in preeclamptic placentae. This study is the first to comprehensively demonstrate abnormalities at the level of the mitochondrion and the molecular pathways controlling mitochondrial content/function in preeclamptic placentae. These aberrations may well contribute to the pathophysiology of preeclampsia by upregulating placental inflammation, oxidative stress, and apoptosis.
KW - glycolysis
KW - mitochondria
KW - mitophagy
KW - oxidative stress
KW - placenta
KW - preeclampsia
KW - Oxidative stress
KW - Mitochondria
KW - Placenta
KW - Preeclampsia
KW - Glycolysis
KW - Mitophagy
U2 - 10.1007/s43032-021-00464-y
DO - 10.1007/s43032-021-00464-y
M3 - Article
C2 - 33523425
SN - 1933-7191
VL - 28
SP - 2186
EP - 2199
JO - Reproductive Sciences
JF - Reproductive Sciences
IS - 8
ER -