Effect of Intrauterine Growth Restriction on Cell Proliferation in the Fetal Cerebellum of the Guinea Pig

Abstract

Intrauterine growth restriction (IUGR) is a risk factor for neurological and behavioral deficits in children although the precise underlying biological mechanisms are unclear. It is also unclear whether IUGR affects cell proliferation in the cerebellum, which is vulnerable to prenatal insults during brain development. The aim of this study is to determine whether IUGR affects the alteration of cell proliferation in the fetal cerebellum and whether this change correlate with reduction in the growth of cerebellum. IUGR was induced via unilateral ligation of the uterine artery in pregnant guinea pigs at 30 days of gestation (dg; term - 67 dg) to produce growth restricted (GR) fetuses. Fetal (control, n=7 and GR, n=7) body and organ weights at 60 dg were measured and Ki67 immunohistochemistry was performed to detect cell proliferation. The width of the external granular layer (EGL) was also measured at 60 dg. The mean body and organ weights of GR fetuses at 60 dg were significantly reduced. The proportion of proliferating cells to the total cell number in the EGL was not different in GR compared with control animals but the width of the EGL was significantly increased in GR animals. These results demonstrate that significant reductions in the growth of the cerebellum do not have a well-defined relationship to cell proliferation in IUGR guinea pig fetuses. In addition, despite there was no difference in the proportion of proliferating to post-mitotic cells between control and GR fetuses in the EGL at 60 dg, the width of the EGL was in￢creased in GR fetuses compared to controls. This could be interpreted as a delay in the process of cell production or migration.