Author:
Hutt Karla J,Shi Zhanquan,Albertini David F,Petroff Brian K
Abstract
Abstract
Background
Environmental toxicants, whose actions are often mediated through the aryl hydrocarbon receptor (AhR) pathway, pose risks to the health and well-being of exposed species, including humans. Of particular concern are exposures during the earliest stages of development that while failing to abrogate embryogenesis, may have long term effects on newborns or adults. The purpose of this study was to evaluate the effect of maternal exposure to the AhR-specific ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat pre-implantation embryos with respect to nuclear and cytoskeletal architecture and cell lineage allocation.
Results
We performed a systematic 3 dimensional (3D) confocal microscopy analysis of rat pre-implantation embryos following maternal exposure to environmentally relevant doses of TCDD. Both chronic (50 ng/kg/wk for 3 months) and acute (50 ng/kg and 1 μg/kg at proestrus) maternal TCDD exposure disrupted morphogenesis at the compaction stage (8–16 cell), with defects including monopolar spindle formation, f-actin capping and fragmentation due to aberrant cytokinesis. Additionally, the size, shape and position of nuclei were modified in compaction stage pre-implantation embryos collected from treated animals. Notably, maternal TCDD exposure did not compromise survival to blastocyst, which with the exception of nuclear shape, were morphologically similar to control blastocysts.
Conclusion
We have identified the compaction stage of pre-implantation embryogenesis as critically sensitive to the effects of TCDD, while survival to the blastocyst stage is not compromised. To the best of our knowledge this is the first in vivo study to demonstrate a critical window of pre-implantation mammalian development that is vulnerable to disruption by an AhR ligand at environmentally relevant doses.
Publisher
Springer Science and Business Media LLC
Reference43 articles.
1. Bock KW, Kohle C: Ah receptor: dioxin-mediated toxic responses as hints to deregulated physiologic functions. Biochem Pharmacol. 2006, 72: 393-404. 10.1016/j.bcp.2006.01.017.
2. Pelclova D, Fenclova Z, Preiss J, Prochazka B, Spacil J, Dubska Z, Okrouhlik B, Lukas E, Urban P: Lipid metabolism and neuropsychological follow-up study of workers exposed to 2,3,7,8-tetrachlordibenzo-p-dioxin. Int Arch Occup Environ Health. 2002, 75 (Suppl): S60-66.
3. Baccarelli A, Mocarelli P, Patterson DG, Bonzini M, Pesatori AC, Caporaso N, Landi MT: Immunologic effects of dioxin: new results from Seveso and comparison with other studies. Environ Health Perspect. 2002, 110: 1169-1173.
4. Pesatori AC, Consonni D, Bachetti S, Zocchetti C, Bonzini M, Baccarelli A, Bertazzi PA: Short- and long-term morbidity and mortality in the population exposed to dioxin after the "Seveso accident". Ind Health. 2003, 41: 127-138.
5. Birnbaum LS: Developmental effects of dioxins. Environ Health Perspect. 1995, 103 (Suppl 7): 89-94. 10.2307/3432515.
Cited by
45 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献