Effects of Maternal Hypoxia on Incorporation of 3H-thymidine into DNA of Neural Tube Matrix Cells in the Mouse Embryo (An Autoradiographic Study)

Abstract

The effect of maternal hypoxia on DNA synthesis of neural tube matrix cells has been studied in the ten-day old mouse embryo. The experiments were carried out by means of the autoradiographic technique. The relative uptake of 3-H-thymidine into nuclear DNA was determined by means of the silver grain count present in the nuclei and of the labeling index of neural tube matrix cells in the telencephalon of normal and hypoxia-exposed mouse embryo on the 10th day of gestation. The results are summarized as follows; 1. The thymidine incorporation and labeling index were noticeably reduced under maternal hypoxia of 6 percent O2 for 1 hour. When 3-H-thymidine was injected immediately following hypoxia for 6 hours, matrix cells showed almost normal thymidine uptake and labeling index. However, when thymidine was injected 2 hours after the same hypoxia, the matrix cells showed a definite reduction of thymidine incorporation and also of labeling index. There were regional differences in reduction of nuclear DNA synthesis throughout the cerebral structure, and it was most marked in the telencephalon in this developmental stage. The matrix cells in the di-, mes- and metencephalon appeared less or not at all affected by maternal hypoxia. 2. In mouse embryo exposed to hypoxia of 6 percent O2 for 6 hours on the 7th day of gestation and sacrificed 1 hour after thymidine injection on the 10th day, matrix cells showed a marked reduction of grain count and an increase of labeling index. The effect was larger than that seen on the 8th or 9th day of gestation. 3. Qualitative examination revealed focal loss of 3-H-thymidine label around pyknotic nuclei in the neural tube of some of the embryos after hypoxia of 6 percent O2 for 6 hours. 4. The significance of the disturbance of DNA synthesis of embryonic neural tube cells by maternal hypoxia was briefly discussed in relation to teratogenesis.