期刊
REPRODUCTIVE TOXICOLOGY
卷 68, 期 -, 页码 171-190出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2016.07.006
关键词
Hexavalent chromium; Placenta; Trophoblasts; Apoptosis
资金
- National Institute of Environmental Health Sciences (NIEHS) [ES020561-01, ES025234-01A1]
- Center for Translational Environmental Health Research (CTEHR) [P30ES023512]
- CTEHR
- NIH-NCRR [1 S10 RR22532-01]
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 (50 ppm K2Cr2O7) 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. (C) 2016 Elsevier Inc. All rights reserved.
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