Biomedical Engineering Reference
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lacking; where present the optic cup ectoderm was thin. These finding
are in agreement with the observations of methanol-induced anoph-
thalmia and microphthalmia in this mouse strain by Rogers et al. (2004).
Degitz et al. (2004a) also reported that there were fewer neural crest
cells in the mid- and hindbrain regions in methanol-treated embryos on
GD 8.
Degitz et al. (2004a) also examined the effects of methanol on
development of the cranial nerves and ganglia using immuno-
histochemical visualization of these structures. Dose-related abnormal-
ities in the development of the cranial nerves and ganglia were seen
after maternal methanol treatment on GD 7. On GD 9, extensive cell
death was evident in areas populated by the neural crest, including the
forming cranial ganglia. Development of ganglia V, VIII, and IX was
reduced in a dose-related manner. Ganglia VII and X exhibited reduced
development only at the highest dose (4.9 g/kg). Also at this dose, the
brain and face were poorly developed and the brachial arches were
reduced in size or virtually absent. Flow cytometry of dissociated nuclei
from the head regions of the embryos at GD 8 did not show an effect on
the proportion of cells in S-phase.
5.3.5.2 In Vitro Studies
Abbott et al. (1995) examined patterns of cell
death in rat and mouse embryos exposed to methanol in culture. Early
somite stage embryos were exposed to dysmorphogenic concentrations
of methanol and observed for cell death using a modified Feulgen
whole-mount staining procedure, which allows nuclei throughout the
embryo to be viewed in situ. Confirming the results of Andrews et al.
(1993a), methanol retarded growth and development (including delayed
neural tube closure) of both rat and mouse embryos, and mouse
embryos were affected at lower concentrations. Increased cell death
was observed in specific regions of the forebrain, visceral arches, and
optic placodes in both species.
The effects of methanol on palatogenesis in vitro were examined and
compared to effects of ethanol by Abbott et al. (1994). Mid-craniofacial
tissues from GD-12 CD-1 mouse embryos were cultured in serum-free
medium for 4 days. Exposure to 0-20mg/ml methanol for 6 hours,
12 hours, 1 or 4 days resulted in a concentration and time-dependent
