TY - JOUR
T1 - Placental mitochondrial dysfunction with metabolic diseases
T2 - Therapeutic approaches
AU - Hebert, Jessica F.
AU - Myatt, Leslie
N1 - Funding Information:
The authors would like to thank Dr. Luis Sobrevia of Pontificia Universidad Católica de Chile for his invitation to submit this review. Figs. 2 and 3 were created with assistance from the OHSU academic license of Biorender (http://www.biorender.com). The authors were supported by the National Institutes of Health (NIH) (Grant HD095610) Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Project Grant 5R01HD095610 (LM).
Funding Information:
The authors would like to thank Dr. Luis Sobrevia of Pontificia Universidad Católica de Chile for his invitation to submit this review. Figs. 2 and 3 were created with assistance from the OHSU academic license of Biorender ( http://www.biorender.com ). The authors were supported by the National Institutes of Health (NIH) (Grant HD095610 ) Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Project Grant 5R01HD095610 (LM).
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Both obesity and gestational diabetes mellitus (GDM) lead to poor maternal and fetal outcomes, including pregnancy complications, fetal growth issues, stillbirth, and developmental programming of adult-onset disease in the offspring. Increased placental oxidative/nitrative stress and reduced placental (trophoblast) mitochondrial respiration occur in association with the altered maternal metabolic milieu of obesity and GDM. The effect is particularly evident when the fetus is male, suggesting a sexually dimorphic influence on the placenta. In addition, obesity and GDM are associated with inflexibility in trophoblast, limiting the ability to switch between usage of glucose, fatty acids, and glutamine as substrates for oxidative phosphorylation, again in a sexually dimorphic manner. Here we review mechanisms underlying placental mitochondrial dysfunction: its relationship to maternal and fetal outcomes and the influence of fetal sex. Prevention of placental oxidative stress and mitochondrial dysfunction may improve pregnancy outcomes. We outline pathways to ameliorate deficient mitochondrial respiration, particularly the benefits and pitfalls of mitochondria-targeted antioxidants.
AB - Both obesity and gestational diabetes mellitus (GDM) lead to poor maternal and fetal outcomes, including pregnancy complications, fetal growth issues, stillbirth, and developmental programming of adult-onset disease in the offspring. Increased placental oxidative/nitrative stress and reduced placental (trophoblast) mitochondrial respiration occur in association with the altered maternal metabolic milieu of obesity and GDM. The effect is particularly evident when the fetus is male, suggesting a sexually dimorphic influence on the placenta. In addition, obesity and GDM are associated with inflexibility in trophoblast, limiting the ability to switch between usage of glucose, fatty acids, and glutamine as substrates for oxidative phosphorylation, again in a sexually dimorphic manner. Here we review mechanisms underlying placental mitochondrial dysfunction: its relationship to maternal and fetal outcomes and the influence of fetal sex. Prevention of placental oxidative stress and mitochondrial dysfunction may improve pregnancy outcomes. We outline pathways to ameliorate deficient mitochondrial respiration, particularly the benefits and pitfalls of mitochondria-targeted antioxidants.
KW - Antioxidants
KW - Gestational diabetes
KW - Mitochondria
KW - Obesity
KW - Oxidative stress
KW - Placenta
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U2 - 10.1016/j.bbadis.2020.165967
DO - 10.1016/j.bbadis.2020.165967
M3 - Review article
C2 - 32920120
AN - SCOPUS:85091805084
SN - 0925-4439
VL - 1867
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 1
M1 - 165967
ER -