Differential permeability of murine visceral yolk sac to thymidine and to hydroxyurea.

Mouse embryos at the 10–12-somite stage of development were excised from the uterus either with or without the encapsulating visceral yolk sac and were incubated in vitro in 3 × 10^?7M thymidine (methyl-T, 5 μCi/ml) for 30 min or in 4 × 10^?3M hydroxyurea for 45 min with ³H]thymidine present for the last 30 min. Radioautograms of nuclei of neural epithelium enabled an estimate of the effectiveness of the barrier imposed by the visceral yolk sac membrane to the passage of thymidine and hydroxyurea.Labeling of nuclei in the neural epithelium showed that the visceral yolk sac caused a 44% decrease in frequency and a 51% decrease in intensity of label. Hydroxyurea inhibited labeling by 15% in frequency and 37% in intensity irrespective of the presence or absence of visceral yolk sac. These results show that hydroxyurea and the presence of visceral yolk sac independently interfered with labeling of the neural epithelium by thymidine and that visceral yolk sac caused a proportionally greater retardation of label than did hydroxyurea.Nuclei of the endodermal epithelium of the intervening yolk sac, following exposure to hydroxyurea, showed a labeling decrease of 44% in frequency and 77% in intensity. The inhibitory effect of hydroxyurea on yolk sac labeling, however, did not alter yolk sac permeability to hydroxyurea. The results indicate that the visceral yolk sac, by offering no detectable barrier to hydroxyurea, permits prompt teratogenic action of hydroxyurea directly upon the embryo and suggest that the visceral yolk sac is a likely candidate to account for reports that the 8.5-day mouse embryo in situ fails to label with radioisotopic thymidine.