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At least 793 records · Page 44Linked to original sources
PubMed1981

The effect of ethanol and acetaldehyde on DNA synthesis in growing cells and on fetal development in the rat.

Incorporation of 3H-thymidine into DNA was significantly diminished by treatment with ethanol and acetaldehyde in regenerating rat liver, rat cells in culture, and rat fetal tissues. Reduced incorporation was especially marked in the fetal central nervous system and was observed with both compounds at levels similar to those reported to occur in human alcoholics. The reduced incorporation of 3H-thymidine into fetal DNA, together with the increased fetal mortality observed in dams treated specifically with acetaldehyde during pregnancy, suggests that acetaldehyde is implicated in the mechanism of teratogenesis associated with the fetal alcohol syndrome.

Acetaldehyde↗
PubMed1994

Investigations of fetal development models for prenatal drug exposure and schizophrenia. Prenatal d-amphetamine effects upon early and late juvenile behavior in the rat.

Recent evidence suggests that mid-pregnancy is a critical period for production of fetal abnormalities that cause behavioral and neuropathological changes in adult offspring. The present experiments provide an animal model of these effects by treating pregnant Sprague-Dawley rats during gestational days 11-14 with d-amphetamine (AM). Offspring were tested for neurological signs, foraging activity, reversal learning, and sensitivity to amphetamine challenge. In the Early Juvenile period, postnatal days (PND) 20-30, female AM offspring initially showed reductions in rearing, holepoking, and midfield activity. On later trials, and as young adults, AM females showed signs of locomotor hyperactivity despite continued poor foraging efficiency, and were also more sensitive to a 1.0 mg/kg d-amphetamine challenge. AM males showed initially slower and more perseverative responding than controls, but then developed excessive response switching. These changes continued during tests for Retention, Reversal, and Extinction in the Late Juvenile/Early Adult stage (PND 50-90), when both AM-exposed sexes showed increased eating time, significantly more perseverative lateral turning preference (right or left), and slower reversal learning than controls. Behavioral data were consistent with aberrations in thalamo-frontal and mesolimbic/nigrostriatal projection systems that have been reported in AM animals and which are also affected by maternal drug abuse and schizophrenia.

Animals↗
PubMed1998

Retinoic acid responsiveness of cells and tissues in developing fetal limbs evaluated in a RAREhsplacZ transgenic mouse model.

Limb morphogenesis is a complex phenomenon in which retinoids play an important role. Abnormal maternal retinoid levels from high oral doses cause fetal malformations, including abnormalities of the musculoskeletal system. Our purpose was to identify the retinoid-responsive cells in bone and cartilage during limb development by using a transgenic line of mice containing a reporter gene insert consisting of a retinoic acid response element linked to an Escherichia coli beta-galactosidase gene. Transgenic fetuses from day 11.5 after conception to birth (day 20) were analyzed histologically. Retinoid-responsive cells and tissues were first seen in the limb bud at 12.5 days in the webs between the forming digits. The webs stained maximally at 14.5 days, after which staining intensity subsided. Staining in the muscles was detectable at 13.5 days, at a stage coinciding with myoblast fusion. Specific regions of perichondrium and periosteum also stained at this stage. Occasional staining was observed in individual chondroblasts in all chondrogenic regions, including hypertrophic chondroblasts and certain articular surfaces of developing joints. Staining of these tissues decreased in intensity in subsequent stages. Osteoclasts started to express beta-galactosidase at 15.5 days and continued to stain into maturity. Our results indicate that specific subsets of cells respond to retinoids at specific stages in the course of normal limb development. In hypertrophic chondrocytes and cells in the webs and joints that display such a response, retinoid-induced effects may be linked to cell death that occurs in these regions. Staining in muscle, perichondrium, and periosteum may reflect retinoid-induced effects associated with cell differentiation and growth. These results suggest that retinoids play a role in a variety of tissues, including bone and cartilage, at specific stages during morphogenesis.

Animals↗
PubMed1984

Sex-related differences in cellular composition and surfactant synthesis of developing fetal rat lungs.

Differences in pulmonary surfactant production by male and female fetuses in late gestation have been suggested, but the precise relationship of these findings to the changing cellular populations in the lung as development progresses has not been investigated previously. Using sexed rat littermates from Day 18 to 22 of gestation, we correlated the epithelial, endothelial, and interstitial cell composition of the lung with disaturated phosphatidylcholine (DSPC) content and with the incidence of lamellar bodies in epithelial cells and air sacs. At Days 19 and 20, female rat lungs had a higher content of DSPC than did the lungs of male littermates. At Days 20 and 21, more cuboidal epithelial cells of female fetuses contained lamellar bodies, and more air sacs in the female lung contained lipid material, than was observed in males. Sex-related differences in lung structure were seen even earlier. From Day 18 to Day 20, there was a greater proportion of epithelial cells in female lungs than in the lungs of male littermates; just before birth the cellular composition was similar. The results show that differentiation of epithelium with lamellar body formation and DSPC production occurs sooner in females. However, it is suggested that a sex-related difference in lung development occurs much earlier in the female at the onset of a phase of epithelial growth.

Animals↗