Some teratogenic properties of ethanol and acetaldehyde in C57BL/6J mice: Implications for the study of the fetal alcohol syndrome

Abstract

To investigate the teratogenic effect of acute alcohol exposure, pregnant C57BL/6J mice were exposed to 25% ethanol (either two doses of 2.9g/kg or one dose 5.8g/kg) during the organogenic period either by intraperitoneal injections or by intubation. The incidence of malformations varied according to (1) the stage of embryonic development at the time of exposure, (2) the route of administration of the alcohol, and (3) the amount of alcohol given and the time period over which it was administered. Oral doses of alcohol were teratogenic although less so than the same dose given intraperitoneally, and two intraperitoneal doses four hours apart produced significantly more malformation than the same two doses six hours apart. The primary metabolite of alcohol, acetaldehyde, was also investigated for its teratogenicity. It was found that one or two doses of four percent acetaldehyde (0.32g/kg), administered intraperitoneally were teratogenic. A further attempt was made to raise blood acetaldehyde levels by exposing mice to disulfiram, an inhibitor of acetaldehyde dehydrogenase, prior to administration of alcohol. The disulfiram pretreatment did not increase the malformation rate. Treatment with alcohol on day 7 or 8 caused a variety of facial abnormalities, some of which were comparable to those seen in children with fetal alcohol syndrome. Exposure on day 9 or 10 resulted in limb defects. The results suggest that one or more episodes of heavy maternal drinking at critical periods in pregnancy may severely damage the embryo and may produce many features of the fetal alcohol syndrome.

Detection of in vivo DNA Damage Induced by Ethanol in Multiple Organs of Pregnant Mice Using the Alkaline Single Cell Gel Electrophoresis (Comet) Assay

“…We administered ethanol to pregnant mice on Day 7 of gestation. Some reports show the teratogenic effects of ethanol on mice fetuses, especially external anomalies, when administered to dams on the same period [25]. In this study, the size of the embryos at 24 hr after ethanol treatment was apparently smaller than those in control groups, it is considered that ethanol treatment induced growth inhibition in mice embryos.…”

“…We administered ethanol to pregnant mice on Day 7 of gestation, since it is considered as organogenic period of mice [25]. In this study, significant increases of DNA damage were observed in brain, lung, and embryos of pregnant mice when administered 4 and 8 g/kg ethanol.…”

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“…Webster et al [29] and Rasmussen & Christensen [30] also reported maxillary hypoplasia our study also reported the same. In our study maxillary and mandibular hypoplasia exhibited as either a flat mid face or a narrow snout that can be compared with the typical human FAS features i.e.…”

Gestational exposure to ethanol suppresses msx2 expression in developing mouse embryos

“…This notion has been supported by animal studies. Single intraperitoneal injections of ethanol given to pregnant C57BL͞6J mice between E7 and E11 resulted in craniofacial abnormalities, including exencephaly and hypoplasia of the midfacial region and anomalies of the DiGeorge sequence (68)(69)(70). The onset of expression of msx2 in mouse embryos has been reported to occur as early as E9 and is still expressed as late as E17 (26).…”