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Effect of Maternal Malnutrition on Matrix Cell Proliferation in the Cerebrum of Mouse Embryo: an Autoradiographic Study

Summary: Thirty pregnant mice were undernourished by providing low protein diets (PM) or providing approximately one-third their normal diets (PCM) for 9 days from the 8th to the 16th day of gestation. Another 15 pregnant mice, which were fed a normal diet, served as the control. On the 16th day of gestation, all animals were injected with a single dose of [3H]thymidine and were killed one by one at 1− or 2-hr intervals.Mean litter size was statistically insignificant between the control group and two malnourished groups. There was, however, a significant difference in mean body weight between the control group and two malnourished groups (P < 0.005). The cerebral cortex at this stage of development consisted of three different layers, i.e., the cortical plate, the migratory zone, and the matrix layer. The width of the cortical plate of the malnourished embryos was significantly smaller (P < 0.001). There was, however, no significant difference in width of the migratory zone between the control and the malnourished groups. The width of the matrix layer in PM was significantly smaller (P < 0.001), but that of PCM showed no significant difference from the control (P > 0.1).Coronal section of the brains of the embryos were processed for autoradiography. Labeled cells were found almost exclusively at the matrix layer surrounding the lateral ventricels. Labeling index counted in the matrix layer after 1 or 2 hr of [3H]thymidine injection indicated that more than 30% of the cells in this layer were always synthesizing DNA in each group of embryos. The generation times of the matrix cell, precursor of the neurons, in the matrix layer were approximately 18.5 hr in the control and 21.5 hr and 21.8 hr in the malnourished embryos, thus indicating about 3 hr of prolongation in the latter. DNA synthetic time was about 6.5 hr in the control and 7.0 hr and 7.0 hr in the two malnourished groups. The postduplication time was about 2.5 hr in the control and 3.0 hr and 3.5 hr in the malnourished. The preduplication time was about 8.8 hr in the control and 10.6 hr and 10.3 hr in the malnourished.Speculation: Most neurons in the mouse cerebrum are produced at the matrix layer, where active cellular proliferation takes place from the 10th to the 16th days of gestation. Malnutrition during this period caused about 14% prolongation of the generation time of the matrix cell, the precursor of neurons, thus causing a decrease in neuron production. Malnutrition during the first and second trimester may cause similar results in the human embryo.