Journal Article

Sexual dimorphism of mitochondrial function in the hypoxic guinea pig placenta

Song, Hong, Telugu, Bhanu P., Thompson, Loren P.

2019

Overview

Placental hypoxia can stimulate oxidative stress and mitochondrial dysfunction reducing placental efficiency and inducing fetal growth restriction (FGR). We hypothesized that chronic hypoxia inhibits mitochondrial function in the placenta as an underlying cause of cellular mechanisms contributing to FGR. Pregnant guinea pigs were exposed to either normoxia (NMX) or hypoxia (HPX; 10.5% O2) at 25 day gestation until term (65 day). Guinea pigs were anesthetized, and fetuses and placentas were excised at either mid (40 day) or late gestation (64 day), weighed, and placental tissue stored at –80°C until assayed. Mitochondrial DNA content, protein expression of respiratory Complexes I-V, and nitration and activity rates of Complexes I and IV were measured in NMX and HPX male (N = 6 in each treatment) and female (N = 6 in each treatment) placentas. Mitochondrial density was not altered by HPX in either mid- or late-term placentas. In mid gestation, HPX slightly increased expression of Complexes I-III and V in male placentas only, but had no effect on either Complex I or IV activity rates or nitrotyrosine expression. In late gestation, HPX significantly decreased CI/CIV activity rates and increased CI/CIV nitration in male but not female placentas exhibiting a sexual dimorphism. Complex I-V expression was reduced from mid to late gestation in both male and female placentas regardless of treatment. We conclude that chronic HPX decreases mitochondrial function by inhibiting Complex I/IV activity via increased peroxynitrite in a sex-related manner. Further, there may be a progressive decrease in energy metabolism of placental cell types with gestation that increases the vulnerability of placental function to intrauterine stress. Summary Sentence Chronic maternal hypoxia impairs mitochondrial function as an underlying cause of placental dysfunction, which may contribute to altered placental and fetal growth.

• Publisher: Society for the Study of Reproduction,Oxford University Press
• Subject: Animals / DNA, Mitochondrial - metabolism / Female / Fetal Growth Retardation - genetics / Fetal Growth Retardation - metabolism / Fetal Growth Retardation - pathology / Fetal Growth Retardation - physiopathology / Fetal Hypoxia - genetics / Fetal Hypoxia - metabolism / Fetal Hypoxia - pathology / Fetal Hypoxia - physiopathology / Fetal Weight - physiology / Hypoxia / Hypoxia - metabolism / Hypoxia - physiopathology / Male / mitochondria / Mitochondria - physiology / Mitochondrial DNA / Organ Size / Oxidative Stress - physiology / Placenta - metabolism / Placenta - pathology / Placenta - physiopathology / Pregnancy / Prenatal Exposure Delayed Effects - metabolism / Prenatal Exposure Delayed Effects - pathology / Prenatal Exposure Delayed Effects - physiopathology / Reproductive health / respiratory complex / Sex Characteristics