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

SIMPLE SUMMARY: Placental 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. ABSTRACT: 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.