Background: Sex differences in the morphology and function of the hippocampus have been reported in several species. Natural fluctuations of sex hormones during the estrous cycle affect the hippocampal neurogenesis of adult female. This study aimed to investigate the neurogenic changes in the hippocampus at different phases of estrous cycle.

Materials and Methods: Different stages of the estrous cycle of the NMRI mice (6-8) mice were determined by staining of vaginal smears. Also, the qualitative assessment of cell proliferation in the dentate gyrus of hippocampus was performed by Nissl staining and Ki-67 immunostaining marker (Ki-67). The apoptosis was determined using the TUNEL assay. Diameter of the hippocampal vessels was measured at different stages of the estrous cycle.

Results: In microscopic sections stained with Cresyl Violet observed cell density in proestrous stage of estrous cycle was greater than any other stages of the estrous cycle. Comparison of sections stained with immunohistochemistry for Ki-67 staining showed that cell proliferation at proestrous are more than any other stages. The statistical analysis showed that vessel diameter was significantly greater at the proestrous stage than diestrous and metestrous. Also, TUNEL assay showed that cell death in the proestrous stage had the least reactivity.

Conclusion: Proestrous stage of the estrous cycle was associated with increased cell proliferation and vessel diameter as well as reduced cell death in the dentate gyrus of the mice hippocampus.