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Toxics 2018, 6(3), 53; https://doi.org/10.3390/toxics6030053

Intrauterine Exposure to Cadmium Reduces HIF-1 DNA-Binding Ability in Rat Fetal Kidneys

1
Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 07360 Ciudad de México, Mexico
2
Departamento de Sociedad y Política Ambiental, CIIEMAD, Instituto Politécnico Nacional, 07340 Ciudad de México, Mexico
3
Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
4
Department of Physiology, Pathophysiology and Toxicology and ZBAF (Center for Biomedical Education and Research), Faculty of Health-School of Medicine, Witten/Herdecke University, 58448 Witten, Germany
*
Author to whom correspondence should be addressed.
Received: 11 June 2018 / Revised: 7 August 2018 / Accepted: 29 August 2018 / Published: 3 September 2018
(This article belongs to the Special Issue Cadmium Sources and Toxicity)
Full-Text   |   PDF [941 KB, uploaded 3 September 2018]   |  

Abstract

During embryonic development, some hypoxia occurs due to incipient vascularization. Under hypoxic conditions, gene expression is mainly controlled by hypoxia-inducible factor 1 (HIF-1). The activity of this transcription factor can be altered by the exposure to a variety of compounds; among them is cadmium (Cd), a nephrotoxic heavy metal capable of crossing the placenta and reaching fetal kidneys. The goal of the study was to determine Cd effects on HIF-1 on embryonic kidneys. Pregnant Wistar rats were exposed to a mist of isotonic saline solution or CdCl2 (DDel = 1.48 mg Cd/kg/day), from gestational day (GD) 8 to 20. Embryonic kidneys were obtained on GD 21 for RNA and protein extraction. Results show that Cd exposure had no effect on HIF-1α and prolyl hydroxylase 2 protein levels, but it reduced HIF-1 DNA-binding ability, which was confirmed by a decrease in vascular endothelial growth factor (VEGF) mRNA levels. In contrast, the protein levels of VEGF were not changed, which suggests the activation of additional regulatory mechanisms of VEGF protein expression to ensure proper kidney development. In conclusion, Cd exposure decreases HIF-1-binding activity, posing a risk on renal fetal development. View Full-Text
Keywords: cadmium; embryonic kidneys; HIF-1; intrauterine exposure cadmium; embryonic kidneys; HIF-1; intrauterine exposure
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Jacobo-Estrada, T.; Cardenas-Gonzalez, M.; Santoyo-Sánchez, M.P.; Thevenod, F.; Barbier, O. Intrauterine Exposure to Cadmium Reduces HIF-1 DNA-Binding Ability in Rat Fetal Kidneys. Toxics 2018, 6, 53.

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