Reproductive consequences of oral arsenate exposure during pregnancy in a mouse model.
BACKGROUND
The second most common of all structural birth defects, neural tube defects (NTDs), affect approximately 2.6/1,000 births worldwide, and 1/1,000 births in the United States. Of the many environmental agents suspected of being teratogenic, arsenic (As) is capable of inducing NTDs in laboratory animals.


METHODS
We evaluated the teratogenicity of oral exposure on embryonic day (E) 7.5 and E:8.5 to As 4.8, 9.6, or 14.4 mg/kg (as sodium arsenate) in an inbred mouse strain, LM/Bc/Fnn, that does not exhibit spontaneous neural tube malformations. Control and arsenic-treated dams (20 per treatment group) were weighed daily, and evaluated for signs of maternal toxicity. Fetuses were evaluated for soft tissue and skeletal malformations.


RESULTS
There was no maternal toxicity as evidenced by losses in maternal body weight following As treatment. However, liver weights were lower in all As-treated groups, suggesting hepatotoxicity due to As exposure. The number of litters affected with an NTD (exencephaly) in each treatment group was: 0, 1, 5, and 9 for control, As 4.8, 9.6, or 14.4, respectively, which exhibited a positive linear trend. There was evidence for trends between As dose and the number of litters displaying vertebral (p<0.001) and calvarial (p<0.01) abnormalities, components of the axial skeleton. Mean fetal weight of all As-treated groups was significantly less than in control.


CONCLUSIONS
In our model, maternal oral treatment with As induced NTDs. It also significantly increased the frequency of axial skeletal anomalies in the offspring exposed in utero, and reduced mean fetal weight, without evidence of maternal toxicity.
Hill
Denise S
DS
Interdisciplinary Faculty of Toxicology, Texas A&M University, College Station, Texas, USA.
Wlodarczyk
Bogdan J
BJ
Finnell
Richard H
RH
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D001149:Arsenates / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D020567:Fetal Weight / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D018811:Maternal Exposure; D051379:Mice; D008815:Mice, Inbred Strains; D009436:Neural Tube Defects / Q000139:chemically induced* / Q000196:embryology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*
D001149:Arsenates; D013723:Teratogens; C009277:sodium arsenate