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Ozone-induced fetal growth restriction in rats is associated with sexually dimorphic placental and fetal metabolic adaptation.
Citation:
Miller, C., J. Dye, A. Henriquez, E. Stewart, K. Lavrich, G. Carswell, H. Ren, D. Freeborn, S. Snow, Mette C. Schladweiler, J. Richards, Prasada Rao Kodavanti, A. Fisher, B. Chorley, AND U. Kodavanti. Ozone-induced fetal growth restriction in rats is associated with sexually dimorphic placental and fetal metabolic adaptation. Molecular Metabolism. Elsevier B.V., Amsterdam, Netherlands, 42:101094, (2020). https://doi.org/10.1016/j.molmet.2020.101094
Impact/Purpose:
The importance of the placenta in mediating pre- and post-natal consequences of fetal growth restriction has been increasingly recognized. However, the influence of placental sexual dimorphism on driving these outcomes has received little attention. Herein, we report that the male placenta in a rodent model of growth restriction upregulates mitochondrial metabolism that likely initiates a sequela of adaptations that promote poor nutrient availability and adiposity in the male fetus. By contrast, the female growth-restricted placenta expresses protective mechanisms (e.g., autophagy) that may serve to increase nutrient availability to support fetal metabolic development.
Description:
The importance of the placenta in mediating the pre- and post-natal consequences of fetal growth restriction has been increasingly recognized. However, the influence of placental sexual dimorphism on driving these outcomes has received little attention. The purpose of this study was to characterize how sex contributes to the relationship between placental metabolism and fetal programming utilizing a novel rodent model of growth restriction. Methods Fetal growth restriction was induced by maternal inhalation of 0.8 ppm ozone (4 h/day) during implantation receptivity (gestation days [GDs] 5 and 6) in Long-Evans rats. Control rats were exposed to filtered air. At GD 21, placental and fetal tissues were obtained for metabolic and genomic assessments. Results Growth-restricted male placentae exhibited increased mitochondrial biogenesis, increased oxygen consumption, and reduced nutrient storage. Male growth-restricted fetuses also had evidence of reduced adiposity and downregulation of hepatic metabolic signaling. In contrast, placentae from growth-restricted females had elevated markers of autophagy accompanied by an observed protection against hepatic metabolic perturbations. Despite this, growth restriction in females induced a greater number of hypothalamic gene and pathway alterations compared to growth-restricted males. Conclusions Increases in mitochondrial metabolism in growth-restricted male placentae likely initiates a sequela of adaptations that promote poor nutrient availability and adiposity. Divergently, the female placenta expresses protective mechanisms that may serve to increase nutrient availability to support fetal metabolic development. Collectively, this work emphasizes the importance of sex in mediating alterations in placental metabolism and fetal programming. Keywords: growth restriction placenta sex differences ozone developmental origins of health and disease
URLs/Downloads:
DOI: Ozone-induced fetal growth restriction in rats is associated with sexually dimorphic placental and fetal metabolic adaptation.