Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Internet Explorer is no longer a supported browser.

This website may not display properly with Internet Explorer. For the best experience, please use a more recent browser such as the latest versions of Google Chrome, Microsoft Edge, and/or Mozilla Firefox. Thank you.

Your Environment. Your Health.

Progress Reports: Texas A&M University: Sensitive Genotypes to Arsenic as a Model Environmental Teratogen

Superfund Research Program

Sensitive Genotypes to Arsenic as a Model Environmental Teratogen

Project Leader: Richard H. Finnell (Baylor College of Medicine)
Grant Number: P42ES004917
Funding Period: 2000-2008

Progress Reports

Year:   2007  2006  2005  2003  2002  2001  2000 

The second most common of all structural birth defects, neural tube defects (NTDs), affect approximately 2.6/1000 births worldwide and 1/1000 births in the United States, causing serious physical disability and death. Arsenite and arsenate are suspect reproductive toxicants and are possibly teratogens in humans; however, epidemiological studies have fallen short of a conclusive association. Arsenate injected intraperitoneally (IP) to gravid laboratory rodents (mouse, rat, and hamster) during neural tube closure induces NTDs. In order to establish the teratogenic risk conferred by ingestion, the most common environmental exposure route, Dr. Finnell evaluated the teratogenicity of oral exposure during neural tube closure to 4.8, 9.6, and14.4 mg/kg (sodium arsenate) in an inbred mouse strain, LM/Bc/Fnn, that does not exhibit spontaneous neural tube malformations. Dams (20 per treatment group) were weighed daily, and evaluated for signs of maternal toxicity. Fetuses were evaluated for soft tissue and skeletal malformations. There was no evidence of maternal toxicity and the number of live fetuses affected with an NTD was 0 (0.0%), 1 (0.5%), 7 (4.0%), and 15 (8.2%) in animals treated with 0 (water treated control), 4.8, 9.6, and 14.4 mg/kg sodium arsenate, respectively. The results exhibited a positive linear trend (p< 0.0001). There was also evidence for linear trends in the relationships between the dose of arsenate and anomalies involving several components of the axial skeleton (sternebral, p< 0.0003; rib, p< 0.0002; vertebral, p< 0.0001; and calvarial, p< 0.0001). In Finnell's model system, maternal oral treatment with arsenate caused exencephaly and significantly increased the axial skeletal variations and malformations in the offspring exposed in utero, without evidence of maternal toxicity.

Dr. Finnell also evaluated the teratogenicity of maternal IP exposure to 9.6 mg/kg of sodium arsenate during neural tube closure in LM/Bc/Fnn mice. Arsenate exposure caused a rate of nearly 100% NTDs (100%, p<0.0001). Embryos were fixed and the anterior neural tube evaluated via electron microscopy for mitochondrial morphology with the assistance of the Image Analysis Core facility. Arsenate-exposed anterior neural tube tissue displayed mitochondrial morphological alterations characterized by disorganized cristae and the mechanisms of these effects were also investigated.

Back
to Top