Sequence of developmental alterations following acute ethanol exposure in mice: craniofacial features of the fetal alcohol syndrome.

The typical facial features of the fetal alcohol syndrome (FAS) were induced in C57B1/6J mice with acute maternal ethanol administration at gastrulation stages of embryonic development. These features include microcephaly, microphthalmia, short palpebral fissures, deficiencies of the philtral region, and a long upper lip. Scanning electron microscopy (SEM) analysis of embryos 24 hours following initial ethanol exposure at 7 days 0 hours of gestation revealed an obvious size reduction in the neural plate, which was particularly noticeable in the forebrain region. As expected, deficiencies in neural plate development at these early stages result in abnormal brain and eye formation. SEM analysis of later embryonic stages revealed the development of closely set olfactory placodes with resultant deficiencies in the medial nasal prominences (that area responsible for forming the philtral region of the upper lip, the alveolar ridge contained the upper incisors, and the anterior portion of the hard palate--the primary palate). Cleared skeletal preparations of affected newborns had marked premaxillary bone deficiencies. One of the most prevalent known human teratogens has a major malformation-inducing effect on gastrulating embryos, a developmental stage present in human embryos prior to pregnancy recognition by most women.