Sex differences in the stereological parameters of the hippocampal dentate gyrus of the guinea pig before puberty

Studies in rats and mice have shown several sex-dependent functional and structural differences in the hippocampal region, a brain structure playing a key role in learning and memory. The aim of the present study was to establish whether sex differences exist prior to puberty in the stereological parameters of the dentate gyrus in the guinea-pig, a long-gestation rodent, whose brain is at a more advanced stage of maturation at birth than the rat and mouse. The number of granule cells and volumes of the granule cell layer, molecular layer and hilus were evaluated in Nissl-stained brains of neonatal (15-16 days old) and peripubescent (45-46 days old) guinea-pigs. Based on a pilot study, the optical disector method was preferred to the optical fractionator method to estimate cell number. For volume (V-ref) estimation with the Cavalieri principle, contour tracing was preferred to the point counting method, as the latter appeared to underestimate volumes. The results showed that neonatal males had more granule cells than females in both the dorsal and ventral dentate gyrus and a larger volume in all layers. Peripubescent males had a larger volume of the granule cell layer than females in both the dorsal and ventral dentate gyrus, more granule cells in the ventral dentate gyrus, a larger volume of the hilus in both the dorsal and ventral dentate gyrus and a larger volume of the molecular layer in the ventral dentate gyrus. The results show that sex differences are present in the guinea-pig dentate gyrus prior to puberty and go in the same direction at both investigated ages, with males exhibiting more granule cells and larger volumes than females. The widespread distribution of these sex differences suggests that in the guinea-pig, similarly to other rodents, hippocampus-dependent functions may be sexually dimorphic.