Biomedical subjects

T W Sadler

Publications and source records attributed to T W Sadler.

75 records · Page 5Linked to original sources

PubMed1976

Biosynthesis of DNA, RNA and proteins by mouse embryos cultured in the presence of a teratogenic dose of chlorambucil.

The effect of chlorambucil on the rates of DNA, RNA, and protein synthesis in mouse embryos was investigated using a system of whole embryo culture. Embryos were isolated on the 11th day of gestation (33 +/- 3 somites) and grown in culture media for periods of 4-8 h. Reichert's membrane and most of the placental tissue was removed leaving only the amnion and visceral yolk-sac surrounding the embryo. In the presence of teratogenic doses of chlorabucil (15 mug/ml) the rate of DNA synthesis was significantly decreased at 4 and 8 h. RNA and protein synthesis were not inhibited at either of these times. A trend toward decreasing rates of protein synthesis at some time beyond 8 h was noted, but not tested.

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PubMedDate not supplied

Serotonin uptake in the ectoplacental cone and placenta of the mouse.

The neurotransmitter serotonin (5-HT) was localized in the ectoplacental cone (EPC) and placenta of the day 9-12 (E9-12) mouse embryo in vivo and in whole embryo cultures, using immunocytochemistry with a specific 5-HT antiserum. In uncultured conceptuses, 5-HT immunoreactivity (5-HT IR) was most intense in the EPC at E9 (2-7 somites), particularly in giant cells around the periphery. Nuclear staining was observed in lightly staining giant cells and in small cells in the core of the cone. By E10 (18-24 somites) 5-HT IR in the placenta was less intense and almost exclusively limited to giant cells, where it was localized to chromatin-like material in nuclei. The same pattern and level of 5-HT IR persisted through E12. In the placenta, 5-HT IR appeared to be most intense in giant cells located near aggregations of platelets in decidual blood vessels. 5-HT IR was enhanced in cultured conceptuses, and further increased when exogenous 5-HT was added to the culture medium. Immunoreactivity was greatly reduced by adding the 5-HT uptake inhibitor fluoxetine to the culture medium, or culturing conceptuses in medium containing 5-HT depleted rat serum. Thus, 5-HT was apparently taken up from the culture medium. In conceptuses exposed to exogenous 5-HT, immunoreactivity in the placenta appeared as a gradient from the giant cells to the inner layers, suggesting that these cells may transport 5-HT toward the embryo. No evidence of 5-HT synthesis by the EPC/placenta was found. These results suggest that 5-HT present in the EPC/placenta is due to uptake, not synthesis. Possible sources and functions of 5-HT in the developing placenta are discussed.

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PubMedDate not supplied

NIEHS/EPA Workshops. Growth and differentiation factors.

The work group identified a number of research areas where they felt there were significant data gaps where additional research was critical to better under standing of the origins of birth defects and to developing ways for their prevention. These included: 1. Studies designed to determine the role of growth and differentiation factors during pre- and postimplantation stages of development. These investigations could include descriptive studies involving the localization and timing of genes expressed and their products, but must also emphasize and include studies involving the function of these molecules and their interactions in normal and abnormal development. 2. Studies designed to develop and utilize models for investigating normal and abnormal development. These approaches could include in vivo and in vitro techniques, such as creation of genetically defined systems and cell, organ, and whole embryo cultures. These technologies should emphasize ways to study the functions of growth and differentiation factors and the effects of environmental factors. 3. Studies designed to identify environmental agents and their targets in embryonic, extraembryonic, and maternal tissues that may play a role in producing developmental abnormalities through peturbations of growth and differentiation factors. 4. Studies designed to determine cellular and molecular mechanisms for protection and recovery from environmental insults.

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