Whole embryo morphometry in teratogen screening.

Current methodology in embryo evaluation involves qualitative assessment of razor blade and paraffin serial sections. Presently, no one has applied existing computerized morphometric techniques to examine embryos. A technique has been developed that enables investigators to section embryos at 150 mu, thereby greatly reducing the number of sections and making morphometric analysis possible. This type of analysis permits the precise volumetric determination of several developing organ systems. The aim of this study was to evaluate the feasibility and sensitivity of whole embryo morphometry in teratogen screening. Cadmium chloride, a well-established teratogen, was chosen because of its ability to induce exencephaly in approximately one-half of offspring while having no observable effects on the remaining exposed embryos. It was found that both exencephalic and normal-appearing cadmium-exposed embryos had significantly smaller total cellular, neuroepithelial, otic vesicle, optic assembly, limb bud, and cardiac mesenchyme volumes when compared to controls. Also, the neuroepithelial volume of the exencephalic embryos was significantly smaller than the normal-appearing cadmium-exposed embryos. These results suggest that in addition to inducing exencephaly, cadmium chloride has an overall inhibitory effect on embryonic growth. We have shown that whole embryo morphometry is a sensitive means of evaluating embryonic growth that permitted determination of cadmium-induced aberrations not discernable by currently employed techniques. In light of these results, we feel this technique shows promise for future investigations of known and suspected teratogens.

Effects of endotoxin on placental labyrinth formation in the golden hamster: a light and electron microscopic study.

Animal studies of endotoxemia during pregnancy have suggested that the placenta is the primary site of action. This study was designed to evaluate the effects of endotoxin at previously established resorptive and teratogenic dose levels during the development of the placenta in the hamster. At the higher dose levels, total necrosis of the placenta was observed within 24 hr after treatment. Formation of fibrin thrombi was only apparent well after the initiation of necrotic events. At the teratogenic dose, a marked decrease in the formation of the placental labyrinth was evident, but invading fetal capillaries and fetal blood cells appeared normal. However, scattered necrotic foci of trophoblastic cells were observed.

Teratogenic effects of endotoxin on the golden hamster.

Gram-negative urinary tract infections in pregnant women have been implicated as causes of maternal endotoxemia and a subsequent higher incidence of malformations in their offspring. A study was performed to evaluate the effects of endotoxin on the development of the golden hamster. Endotoxin was shown to be extremely embryolethal at higher doses and to produce several malformations at lower doses. The pregnant hamster and its developing embryos were observed to be far more sensitive to endotoxin than species examined by other investigators.

Pregnancy and fetal development in hamsters treated with prostaglandin F2 alpha.

The influence of PGF2 alpha on pregnancy and fetal outcome was investigated in the hamster. Following subcutaneous treatment with 50, 100, 200, 400, and 800 micrograms PGF2 alpha prenatal loss was significantly increased only at the highest dose level. The offspring of the treated animals were all alive and normal. Fetal weight was not affected. However, following intravenous injection of 100 and 200 micrograms PGF2 alpha there was a significant reduction in fetal weight, and at the 400 micrograms dose level an increase in fetal indicate that PGF2 alpha is not teratogenic in hamsters despite the apparent greater sensitivity of the hamster embryo to prostaglandin.