title: Chromium VI - Induced developmental toxicity of placenta is mediated through spatiotemporal dysregulation of cell survival and apoptotic proteins.
abstract: Environmental contamination with hexavalent chromium (CrVI) is a growing problem both in the U.S and developing countries. CrVI is a heavy-metal endocrine disruptor; women working in Cr industries exhibit an increased incidence of premature abortion and infertility. The current study was designed to understand the mechanism of CrVI toxicity on placental cell survival/death pathways. Pregnant mothers were treated with or without CrVI (50ppmK2Cr2O7) through drinking water from gestational day (GD) 9.5-14.5, and placentas were analyzed on GD 18.5. Results indicated that CrVI increased apoptosis of trophoblasts, vascular endothelium of the metrial glands and yolk sac epithelium through caspase-3 and p53-dependent pathways. CrVI increased apoptosis in labyrinth and basal zones in a caspase-3-independent manner via AIF, and through an ATM-p53-NOXA-PUMA-p27 network. CrVI downregulated cell survival proteins Bcl-2, Bcl-XL and XIAP in the placenta. CrVI disrupts placental histoarchitecture and increases cell death by spatiotemporal modulation of apoptotic signaling.
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Mail stop TAMU 4458, Texas A&M University, College Station, TX 77843, USA. Electronic address: skbanu@cvm.tamu.edu.
authors.forename: Sakhila K
authors.initials: SK
authors.lastname: Banu
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Mail stop TAMU 4458, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Jone A
authors.initials: JA
authors.lastname: Stanley
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Mail stop TAMU 4458, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Kirthiram K
authors.initials: KK
authors.lastname: Sivakumar
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Mail stop TAMU 4458, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Joe A
authors.initials: JA
authors.lastname: Arosh
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Mail stop TAMU 4458, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Taylor
authors.affiliation: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Mail stop TAMU 4458, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Burghardt
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002857:Chromium / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D018811:Maternal Exposure; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D062211:Spatio-Temporal Analysis
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D002857:Chromium; C074702:chromium hexavalent ion
keywords: Apoptosis; Hexavalent chromium; Placenta; Trophoblasts