Impaired Mitochondrial Function Results from Oxidative Stress in the Full-Term Placenta of Sows with Excessive Back-Fat.

Liang Tian,Jiahe Huang,Peishi Yan,Aiyou Wen

doi:10.3390/ani10020360

Abstract

Simple SummaryPlacental dysfunction associated with maternal obesity has been demonstrated to be a possible detrimental determinant for a reproductive disorder in human and animals such as pigs. Moreover, there exists a substantial amount of evidence supporting that mitochondrial dysfunction associated with obesity contributes to dysfunction of highly metabolic tissues, including adipose, skeletal muscle and placenta. Despite previous reports have demonstrated that back-fat thickness of sows is associated with placental dysfunction, the influences of excessive back-fat on mitochondrial structure and function in porcine placenta still remain elusive. In this study, animal (Landrace) and cell in vitro model (pig placental trophoblasts) were employed to evaluate mitochondrial alterations in the placentas of sows with different back-fat depth. We revealed that excessive back-fat of sows is associated with placental mitochondrial abnormalities corresponding to decreased ATP production and impaired mitochondrial respiration in the placenta. Together, our findings develop the understanding about the impact of excessive back-fat induced oxidative stress on mitochondrial alterations in the pig placenta, which may contribute to generate some strategies in future to improve sow reproduction.The aim of this study was to determine the effect of excessive back-fat (BF) of sows on placental oxidative stress, ATP generation, mitochondrial alterations in content and structure, and mitochondrial function in isolated trophoblasts. Placental tissue was collected by vaginal delivery from BFI (15–20 mm, n = 10) and BFII (21–27 mm, n = 10) sows formed according to BF at mating. Our results demonstrated that excessive back-fat contributed to augmented oxidative stress in term placenta, as evidenced by excessive production of ROS, elevated protein carbonylation, and reduced SOD, GSH-PX, and CAT activities (p < 0.05). Indicative of mitochondrial dysfunction, reduced mitochondrial respiration in cultured trophoblasts was linked to decreased ATP generation, lower mitochondrial Complex I activity and reduced expression of electron transport chain subunits in placenta of BFII sows (p < 0.05). Meanwhile, we observed negative alterations in mitochondrial biogenesis and structure in the placenta from BFII group (p < 0.05). Finally, our in vitro studies showed lipid-induced ROS production resulted in mitochondrial alterations in trophoblasts, and these effects were blocked by antioxidant treatment. Together, these data reveal that excessive back-fat aggravates mitochondrial injury induced by increased oxidative stress in pig term placenta, which may have detrimental consequences on placental function and therefore impaired fetal growth and development.

Highlights

Pregnancy complicated by maternal obesity is associated with an abnormal intrauterine milieu characterized by increased lipid accumulation, augmented oxidative stress, and significant inflammation within the placenta [1,2], resulting in placental dysfunction and the poor pregnancy outcomes in human beings and animals such as pig [3,4]
Consistent with our hypothesis, we demonstrated that excessive back-fat resulted in increased reactive oxygen species (ROS) production, reduced mitochondrial biogenesis, impaired mitochondrial respiration, and mitochondrial abnormalities in content and structure in pig full-term placenta, suggesting excessive back-fat of sows may promote placental mitochondrial dysfunction that is associated with impaired placental function and fetal development
To determine whether changes in placental ATP levels are related to altered mitochondrial respiration, we investigated the effects of excessive back-fat on respiration, maximal respiration and spare capacity compared with cells from BFI group (p < 0.05, mitochondrial function in vitro using cultured cytotrophoblasts (Figure 2B)

Summary

Introduction

Pregnancy complicated by maternal obesity is associated with an abnormal intrauterine milieu characterized by increased lipid accumulation, augmented oxidative stress, and significant inflammation within the placenta [1,2], resulting in placental dysfunction and the poor pregnancy outcomes in human beings and animals such as pig [3,4]. Excessive lipid accumulation has been shown to induce cellular dysfunction through the over production of reactive oxygen species (ROS), mitochondrial dysfunction, and the activation of inflammation in highly metabolic tissues like adipose and skeletal muscle [5,6]. As a significant marker of placental lipotoxicity, oxidative stress can be increased in pregnancy complicated by maternal obesity resulting in placental oxidative injure [11]. Mitochondria, a key energy source for placental function, are the major source of ROS under physiologic conditions

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