Ozone-induced fetal growth restriction in rats is associated with sexually dimorphic placental and fetal metabolic adaptation

被引：16

作者：

Miller, Colette N. ^{[1
,2
]}

Dye, Janice A. ^{[1
]}

Henriquez, Andres R. ^{[2
]}

Stewart, Erica J. ^{[2
]}

Lavrich, Katelyn S. ^{[3
]}

Carswell, Gleta K. ^{[4
]}

Ren, Hongzu ^{[1
]}

Freeborn, Danielle L. ^{[1
]}

Snow, Samantha J. ^{[1
,5
]}

Schladweiler, Mette C. ^{[1
]}

Richards, Judy H. ^{[1
]}

Kodavanti, Prasada R. S. ^{[1
]}

Fisher, Anna ^{[1
]}

Chorley, Brian N. ^{[4
]}

Kodavanti, Urmila P. ^{[1
]}

机构：

[1] US EPA, Publ Hlth & Integrated Toxicol Div, Ctr Publ Hlth & Environm Assessment, Off Res & Dev, 109 TW Alexander Dr,Mail Code B105-02, Res Triangle Pk, NC 27711 USA

[2] US EPA, Oak Ridge Inst Sci & Educ Res Participat Program, 109 TW Alexander Dr,Mail Code B105-02, Res Triangle Pk, NC 27711 USA

[3] NIEHS, Div Natl Toxicol Program, 530 Davis Dr,Keystone Bldg, Durham, NC 27713 USA

[4] US EPA, Biomol & Computat Toxicol Div, Ctr Computat Toxicol & Exposure, Off Res & Dev, 109 TW Alexander Dr,Mail Code B105-02, Res Triangle Pk, NC 27711 USA

[5] ICF Int Inc, 2635 Meridian Pkwy,Suite 200, Durham, NC 27713 USA

来源：

MOLECULAR METABOLISM | 2020年 / 42卷

基金：

美国国家卫生研究院;

关键词：

Growth restriction; Placenta; Sex differences; Ozone; Developmental origins of health and disease; AMNIOTIC-FLUID; LEPTIN; SEX;

D O I：

10.1016/j.molmet.2020.101094

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: 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. (C) 2020 The Authors. Published by Elsevier GmbH.

引用

页数：12

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