Mitochondria-mediated Maternal-fetal Interactions and Consequences of Mitochondrial Dysregulation Indicate New Roles for Mitochondria in Hypertensive Pregnancies

Ricci, Contessa A.; Reid, Danielle Marie; Sun, Jie; Santillan, Donna A.; Santillan, Mark K.; Goulopoulou, Styliani; Phillips, Nicole R.

doi:10.1101/2021.12.18.21268029

“…In fact, elevated mutational loads of circulating cell-free (ccf)-mtDNA have been identified in blood (buffy coat) collected from third trimester patients with PE and gestational hypertension alike. As ccf-mtDNA is often regarded as a marker of systemic inflammation, this result suggests that dysregulated mitochondria from gestational parent origin is a likely contributor to PE pathophysiology [ 139 ]. In vitro studies have shown that treatment of human umbilical vascular endothelial cells (HUVECs) with serum of PE patients or exogenous placenta-mediated factors (sFLT-1 or angiotensin II type 1 autoantibodies), leads to decreased mitochondrial respiratory capacity, increased superoxide formation and induces a glycolytic phenotype [ 79 , 140 , 141 ].…”

Section: Mitochondrial Dysfunction—a Point Of Convergence Across Pree...mentioning

confidence: 99%

Placental Mitochondrial Function and Dysfunction in Preeclampsia

Jahan

¹

,

Vasam

²

,

Green

³

et al. 2023

IJMS

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The placenta is a vital organ of pregnancy, regulating adaptation to pregnancy, gestational parent/fetal exchange, and ultimately, fetal development and growth. Not surprisingly, in cases of placental dysfunction—where aspects of placental development or function become compromised—adverse pregnancy outcomes can result. One common placenta-mediated disorder of pregnancy is preeclampsia (PE), a hypertensive disorder of pregnancy with a highly heterogeneous clinical presentation. The wide array of clinical characteristics observed in pregnant individuals and neonates of a PE pregnancy are likely the result of distinct forms of placental pathology underlying the PE diagnosis, explaining why no one common intervention has proven effective in the prevention or treatment of PE. The historical paradigm of placental pathology in PE highlights an important role for utero–placental malperfusion, placental hypoxia and oxidative stress, and a critical role for placental mitochondrial dysfunction in the pathogenesis and progression of the disease. In the current review, the evidence of placental mitochondrial dysfunction in the context of PE will be summarized, highlighting how altered mitochondrial function may be a common feature across distinct PE subtypes. Further, advances in this field of study and therapeutic targeting of mitochondria as a promising intervention for PE will be discussed.

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“…In fact, elevated mutational loads of circulating cell free (ccf)-mtDNA have been identified in blood (buffy coat) collected from 3rd trimester patients with PE and gestational hypertension alike. As ccf-mtDNA is often regarded as a marker of systemic inflammation, this result suggests that dysregulated mitochondria from gestational-parent origin is a likely contributor to PE pathophysiology [135]. In vitro studies have shown that treatment of human umbilical vascular endothelial cells (HUVECs) with serum of PE patients or exogenous placenta-mediated factors (sFLT-1 or angiotensin II type 1 autoantibodies), leads to decreased mitochondrial respiratory capacity, increased superoxide formation and induced a glycolytic phenotype [74,136,137].…”

Section: Gestational-parent Driven Pe -Predisposing Factors and Mitoc...mentioning

confidence: 99%

Placental Mitochondrial Function and Dysfunction in Preeclampsia

Jahan¹,

Vasam²,

Green³

et al. 2023

Preprint

0

View full text Add to dashboard Cite

The placenta is a vital organ of pregnancy, regulating adaptation to pregnancy, gestational-parent/fetal exchange and ultimately fetal development and growth. Not surprisingly, in cases of placental dysfunction - where aspects of placental development or function become compromised - adverse pregnancy outcomes can result. One common placenta-mediated disorder of pregnancy is preeclampsia (PE), a hypertensive disorder of pregnancy with a highly heterogeneous clinical presentation. The wide array of clinical characteristics observed in pregnant individuals and neonates of a PE pregnancy are likely the result of distinct forms of placental pathology underlying the PE diagnosis, explaining why no one common intervention has proven effective in the prevention or treatment of PE. The historical paradigm of placental pathology in PE highlights an important role for utero-placental malperfusion, placental hypoxia and oxidative stress, and a critical role for placental mitochondrial dysfunction in the pathogenesis and progression of the disease. In the current review, the evidence of placental mitochondrial dysfunction in the context of PE will be summarized, highlighting how altered mitochondrial function may be a common feature across distinct PE subtypes. Further, advances in this field of study and therapeutic targeting of mitochondria as a promising intervention for PE will be discussed.

show abstract

“…In fact, elevated mutational loads of circulating cell free (ccf)-mtDNA have been identified in blood (buffy coat) collected from 3rd trimester patients with PE and gestational hypertension alike. As ccf-mtDNA is often regarded as a marker of systemic inflammation, this result suggests that dysregulated mitochondria from gestational parent origin is a likely contributor to PE pathophysiology [139]. In vitro studies have shown that treatment of human umbilical vascular endothelial cells (HUVECs) with serum of PE patients or exogenous placenta-mediated factors (sFLT-1 or angiotensin II type 1 autoantibodies), leads to decreased mitochondrial respiratory capacity, increased superoxide formation and induced a glycolytic phenotype [79,140,141].…”

Section: Gestational Parent Driven Pe -Predisposing Factors and Mitoc...mentioning

confidence: 99%

Placental Mitochondrial Function and Dysfunction in Preeclampsia

Jahan¹,

Vasam²,

Green³

et al. 2023

Preprint

0

View full text Add to dashboard Cite

The placenta is a vital organ of pregnancy, regulating adaptation to pregnancy, gestational-parent/fetal exchange and ultimately fetal development and growth. Not surprisingly, in cases of placental dysfunction - where aspects of placental development or function become compromised - adverse pregnancy outcomes can result. One common placenta-mediated disorder of pregnancy is preeclampsia (PE), a hypertensive disorder of pregnancy with a highly heterogeneous clinical presentation. The wide array of clinical characteristics observed in pregnant individuals and neonates of a PE pregnancy are likely the result of distinct forms of placental pathology underlying the PE diagnosis, explaining why no one common intervention has proven effective in the prevention or treatment of PE. The historical paradigm of placental pathology in PE highlights an important role for utero-placental malperfusion, placental hypoxia and oxidative stress, and a critical role for placental mitochondrial dysfunction in the pathogenesis and progression of the disease. In the current review, the evidence of placental mitochondrial dysfunction in the context of PE will be summarized, highlighting how altered mitochondrial function may be a common feature across distinct PE subtypes. Further, advances in this field of study and therapeutic targeting of mitochondria as a promising intervention for PE will be discussed.

show abstract

Mitochondria-mediated Maternal-fetal Interactions and Consequences of Mitochondrial Dysregulation Indicate New Roles for Mitochondria in Hypertensive Pregnancies

Cited by 3 publications

References 45 publications

Placental Mitochondrial Function and Dysfunction in Preeclampsia

Placental Mitochondrial Function and Dysfunction in Preeclampsia

Placental Mitochondrial Function and Dysfunction in Preeclampsia

Placental Mitochondrial Function and Dysfunction in Preeclampsia

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