Effects of sodium valproate and oxygen on the craniofacial skeletal pattern in the CD-1 mouse embryo

Growth retardation is a consistent finding in animal studies on the effect of sodium valproate (NaVP) in the embryo. Apart from fetal weight, the state of ossification in the embryo may be regarded as an indication of growth. The present study was to determine what effect sodium valproate at human t...

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Bibliographic Details
Published inJournal of craniofacial genetics and developmental biology Vol. 9; no. 4; p. 339
Main Authors Paulson, R B, Sucheston, M E, Hayes, T G, Weiss, H S
Format Journal Article
LanguageEnglish
Published Denmark 1989
Subjects
Animals
Facial Bones - drug effects
Facial Bones - embryology
Female
Fetal Growth Retardation - chemically induced
Maternal-Fetal Exchange
Mice
Osteogenesis - drug effects
Oxygen - toxicity
Pregnancy
Skull - drug effects
Skull - embryology
Valproic Acid - toxicity
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Summary:Growth retardation is a consistent finding in animal studies on the effect of sodium valproate (NaVP) in the embryo. Apart from fetal weight, the state of ossification in the embryo may be regarded as an indication of growth. The present study was to determine what effect sodium valproate at human therapeutic drug plasma levels had on the craniofacial skeletal pattern in the CD-1 mouse embryo relative to oxygen conditions, drug treatment or the interaction of the two. Two NaVP-filled Alzet osmotic minipumps were implanted subcutaneously on day 5 of gestation for continuous delivery of a total daily dosage of 850 mg/kg for 7 days. During this same time period the dams were also exposed to either normoxic (21% oxygen), hyperoxic (50% oxygen), or hypoxic (12% oxygen) controlled environments. Dams were removed from the oxygen chambers on day 12 and killed on day 18 of gestation. The fetuses were then processed for skeletal evaluation of the craniofacial region. Ossification centers were present in all but six of the skeletal elements studied. The primary ossification delay was in the tympanic bony labyrinth. In addition, there was a decrease in maxillary and mandibular length and cranial base measurements. The greatest toxic effect on the fetus for all skeletal components studied was in the NaVP/hypoxia treated group. This finding suggests that fetal skeletal maturation may be affected by a combination of intrauterine as well as external factors.
ISSN:0270-4145