Effect of Prenatal Exposure to Ethanol on the Cell Cycle Kinetics and Growth Fraction in the Proliferative Zones of Fetal Rat Cerebral Cortex

Abstract

Prenatal exposure to ethanol produces profound changes in the number of neurons in the mature cortex. These changes in neuronal number may reflect ethanol-induced disturbances in early developmental processes, that is in the proliferation of neuronal precursors. Hence, the present study examined the effect of ethanol on cell proliferation in the two neocortical proliferative zones, the ventricular zone (VZ) and subventricular zone (SZ). From gestational day 5 to 21, pregnant rats were fed an ethanol diet (6.7% v/v), pair-fed an isocaloric control diet, or fed chow and water. Pregnant rats were given a series of one to nine injections of bromodeoxyuridine (BrdU). After immunohistochemical processing, the ratio of cells in each proliferative zone that were labeled with BrdU to the total population was determined. The portion of the population that was cycling (growth fraction), the total length of the cell cycle, and the length of the S-phase of the cell cycle were calculated for VZ and SZ cells. Exposure to moderate levels of ethanol has markedly different effects upon the two neocortical proliferative zones. In the VZ, the length of the total cell cycle was significantly greater in ethanol-treated rats than in controls; however, the growth fraction and the length of the S-phase were unaffected by ethanol. In contrast, in the SZ, the growth fraction was significantly greater in ethanol-treated rats, but ethanol had no effect on the length of the total cell cycle or of the S-phase. These differences may underlie the ethanol-induced abnormalities in neuronal generation.