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Biomedical subjects

M Hamburgh

Publications and source records attributed to M Hamburgh.

At least 19 recordsLinked to original sources

Evidence for repair in trypan blue-treated mouse egg cylinders: an electron microscopic study.

The question of whether mammalian fetuses can correct damage induced by teratogens during early stages of embryogenesis was reinvestigated. Toward this purpose female mice were injected on day 6 of gestation with the teratogenic dye trypan blue. Within 6, 24, and 48 hr of exposure to the teratogen, egg cylinders were removed, sectioned, and prepared for electron microscopic analysis. The following organelles were examined: 1) mitochondria, 2) Golgi apparatus, 3) endoplasmic reticulum, and 4) free polysomes. On the ultrastructural level, exposure to trypan blue lead within 6 hr to fragmentation of the endoplasmic reticulum and a depletion of free polysomes in the endoderm of the egg cylinders. In ectodermal cells only the distribution of polysomes was disturbed following exposure to trypan blue. Egg cylinders harvested 24 hr after injection of trypan blue had partially recovered. Their endoplasmic reticulum and polysomes appeared closer to controls. The cells of both germ layers of most egg cylinders obtained 48 hr after injection were indistinguishable from controls when viewed with the electron microscope. No consistent changes were found in mitochondria or Golgi apparatus following trypan blue treatment. It is concluded that mouse embryos appear to be able to correct damage sustained during the egg cylinder stage, and that in spite of earlier injury affecting both germ layers such egg cylinders can develop normally as revealed by microscopic examination.

Abnormalities, Drug-Induced

Development of home orientation in hypothyroid and hyperthyroid rat pups.

In order to assess the effects of perinatal hypothyroidism or hyperthyroidism on the development of an integrated behavioral response, we tested hypothyroid, hyperthyroid, and control pups, as well as pups receiving thyroxine replacement therapy, for the development of the home orientation response. Hypothyroidism was induced in the pups by feeding the pregnant or lactating female a diet of .2% propylthiouracil from Day 15 of gestation to Day 22 postpartum. Pups receiving replacement therapy and pups made hyperthyroid were injected daily with thyroxine, starting at birth. The ability of the pups to initiate and maintain locomotion toward the nest was assessed between Days 4 and 22. Hyperthyroid, control, and replacement therapy pups behaved very similarly on the task, showing a peak in the percentage of pups homing between Days 12 and 16. Hypothyroid pups showed a delay in the peak percentage until Day 20, although the percentage of pups was similar to that found in other treatments. An integrated behavioral response can be delayed by hypothyroidism and still emerge apparently intact at a later age.

Animals

Some additional observations relating to the mechanism of trypan blue induced teratogenesis.

The mechanism and site of teratogenic action of trypan blue on mammalian embryos was reinvestigated. The experiments to be presented include (1) an analysis of the effect of trypan blue treatment on the morphology of the early mouse egg cylinder, (2) a demonstration of the effect of dye treatment on the enzyme acid phosphatase of yolk sac epithelium using histochemical procedures. Results obtained from these experiments indicate that trypan blue injected into mothers on day 7 of gestational age leads, within 12 to 24 hours after treatment, to dramatic abnormalities in 90-95% of egg cylinders examined. The frequency of gross malformations obtained by this treatment is considerably less when litters are examined at later stages of gestation. Acid phosphatase activity in yolk sac epithelium is depressed by the dye treatment, but there is no difference between enzymatically depressed yolk sacs of malformed embryos and yolk sacs surrounding normally appearing litter mates both obtained from trypan blue treated mothers. The hypothesis that trypan blue may exert its teratogenic effect by the direct exposure of egg cylinder stages to the dye, and that some of the egg cylinders affected may subsequently repair, is recommended for further testing.

Abnormalities, Drug-Induced