Neuron loss in the mouse hippocampus following prenatal injection of tritiated thymidine or saline.

To investigate possible effects of injections of tritiated thymidine ([3H]dThd) into pregnant mice or the injection procedure itself on the proliferation of neuronal precursor cells in the fetuses, pregnant mice received intraperitoneal injections of either [3H]dThd or saline on embryonic days 12, 14, and 19, while their offspring remained untreated. A second group of dams was not injected but their male offspring received a subcutaneous injection of again either [3H]dThd or saline on postnatal day 10. Then total numbers of hippocampal pyramidal cells (areas CA1 to CA3) and granular cells (dentate gyrus) were determined stereologically for 20-day-old as well as for 80-day-old male pups. No significant differences were found for the mean total number of pyramidal cells between the investigated groups of pups. However, the mean total number of granular cells was significantly reduced in those groups in which the dams had received an intraperitoneal injection, irrespective of whether [3H]dThd or saline was injected. This revives the repeated warning in the literature to consider the effect of the injection procedure on the developing brain when interpreting possible effects of agents administered during pregnancy.