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The role of the tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) in offspring exposed to prenatal hypoxia

Published online by Cambridge University Press:  18 December 2017

L. M. Reyes ,
A. Shah ,
A. Quon ,
J. S. Morton  and
S. T. Davidge
L. M. Reyes
Affiliation:
Department of Physiology, University of Alberta, Edmonton, AB, Canada Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB, Canada
A. Shah
Affiliation:
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB, Canada
A. Quon
Affiliation:
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada
J. S. Morton
Affiliation:
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB, Canada
S. T. Davidge*
Affiliation:
Department of Physiology, University of Alberta, Edmonton, AB, Canada Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB, Canada
*
*Address for correspondence: S. T. Davidge, Women and Children’s Health Research Institute and Departments of Obstetrics and Gynecology, and Physiology, University of Alberta, 232 HMRC Building, Edmonton, AB, Canada T6G 2S2. (Email sandra.davidge@ualberta.ca)
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Abstract

Exposure to prenatal hypoxia in rats leads to intrauterine growth restriction (IUGR), decreases fetal cardiomyocyte proliferation and increases the risk to develop cardiovascular diseases (CVD) later in life. The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) induces cardiomyocyte proliferation through activation of the fibroblast growth factor-inducible molecule 14 (Fn-14) receptor. The TWEAK/Fn-14 pathway becomes quiescent shortly after birth, however, it becomes upregulated with CVD; suggesting that it could be a link between the increased susceptibility to CVD in pregnancies complicated by hypoxia/IUGR. We hypothesized that offspring exposed to prenatal hypoxia will exhibit reduced cardiomyocyte proliferation due to reduced Fn-14 expression and that the TWEAK/Fn-14 pathway will be expressed in those adult offspring. We exposed pregnant Sprague Dawley rats to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational days 15 to 21. Ventricular cardiomyocytes were isolated from male and female, control and hypoxic offspring at postnatal day 1. Proliferation was assessed in the presence or absence of r-TWEAK (72 h, 100 ng/ml). Prenatal hypoxia was not associated with differences in Fn-14 protein expression in either male or female offspring. Cardiomyocytes from prenatal hypoxic male, but not female, offspring had decreased proliferation compared with controls. Addition of r-TWEAK increased cardiomyocyte proliferation in all offspring. In adult offspring of all groups, the TWEAK/Fn-14 pathway was not detectable. Cardiomyocyte proliferation was reduced in only male offspring exposed to prenatal hypoxia but this was not due to changes in the Fn-14 pathway. Studies addressing other pathways associated with CVD and prenatal hypoxia are needed.

Keywords

cardiomyocyte proliferationprenatal hypoxiaTWEAK
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 6 , December 2018 , pp. 661 - 669
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

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