PMID- 30177602 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2305-6304 (Electronic) IS - 2305-6304 (Linking) VI - 6 IP - 3 DP - 2018 Sep 3 TI - Intrauterine Exposure to Cadmium Reduces HIF-1 DNA-Binding Ability in Rat Fetal Kidneys. LID - 10.3390/toxics6030053 [doi] LID - 53 AB - 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 CdCl(2) (D(Del) = 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-1alpha 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. FAU - Jacobo-Estrada, Tania AU - Jacobo-Estrada T AUID- ORCID: 0000-0001-9682-8627 AD - Departamento de Toxicologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, 07360 Ciudad de Mexico, Mexico. tjacoboe@ipn.mx. AD - Departamento de Sociedad y Politica Ambiental, CIIEMAD, Instituto Politecnico Nacional, 07340 Ciudad de Mexico, Mexico. tjacoboe@ipn.mx. FAU - Cardenas-Gonzalez, Mariana AU - Cardenas-Gonzalez M AUID- ORCID: 0000-0003-4154-6088 AD - Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. mcardenasgonzalez@bwh.harvard.edu. FAU - Santoyo-Sanchez, Mitzi Paola AU - Santoyo-Sanchez MP AD - Departamento de Toxicologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, 07360 Ciudad de Mexico, Mexico. santoyomitzi@gmail.com. FAU - Thevenod, Frank AU - Thevenod F AD - 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. frank.thevenod@uni-wh.de. FAU - Barbier, Olivier AU - Barbier O AUID- ORCID: 0000-0002-0378-3675 AD - Departamento de Toxicologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, 07360 Ciudad de Mexico, Mexico. obarbier@cinvestav.mx. LA - eng GR - PICSA12-086/Secretaria de Ciencia, Tecnologia e Innovacion del Distrito Federal/ GR - 267755/Consejo Nacional de Ciencia y Tecnologia CONACYT/FONCICYT/ GR - 326697/Consejo Nacional de Ciencia y Tecnologia/ PT - Journal Article DEP - 20180903 PL - Switzerland TA - Toxics JT - Toxics JID - 101639637 PMC - PMC6161213 OTO - NOTNLM OT - HIF-1 OT - cadmium OT - embryonic kidneys OT - intrauterine exposure COIS- The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; and in the decision to publish the results. EDAT- 2018/09/05 06:00 MHDA- 2018/09/05 06:01 PMCR- 2018/09/03 CRDT- 2018/09/05 06:00 PHST- 2018/06/11 00:00 [received] PHST- 2018/08/07 00:00 [revised] PHST- 2018/08/29 00:00 [accepted] PHST- 2018/09/05 06:00 [entrez] PHST- 2018/09/05 06:00 [pubmed] PHST- 2018/09/05 06:01 [medline] PHST- 2018/09/03 00:00 [pmc-release] AID - toxics6030053 [pii] AID - toxics-06-00053 [pii] AID - 10.3390/toxics6030053 [doi] PST - epublish SO - Toxics. 2018 Sep 3;6(3):53. doi: 10.3390/toxics6030053.