اثرات تاموکسیفن بر فراساختار و تعداد سلولهای هیپوکامپ جنین و نوزاد The Effects of Tamoxifen on Ultrastructure and the Number of Hippocampal Cells in Rat’s Fetus and Neonate

    Background & Aim: Maternal steroids modulate various functions in the brain. However, tamoxifen(TAM) treatment, as an estrogen antagonist, induces cell death in the hippocampus formation of a prenatal and postnatal rat. Estrogen influences cognitive functions, learning process, aging, vasodilation, angiogenesis, neurogenesis and neuroprotection. The present study deals with the effects of tamoxifen on ultrastructure and morphology of developing hippocampus in rats. Material & Method: In this experimental study, we examined twelve bands of rats in three groups of control, experimental and sham. In each group, there were four age ranges: full-term embryo(E22), one-day newborn(P1), seven-day newborn (P7), and three-week newborn(P21). Full-term animals received four doses of tamoxifen in propylene glycol and their brains were removed 6 hours after the last injection. We studied hippocampal regions such as CA1, CA3, D.G. and subiculum through light and electron microscopy. Statistical significance of the differences was assessed by ANOVA and t-test using SPSS program. A value of P<0.05 was considered significant. Results: The obtained findings reveal a decrease in the density of cells in various regions such as CA1 and subiculum. Electron microscopy showed pyknosis, increased nucleus density, chromatin clumping, mitochondrial inflammation and changes in mitochondria crista, mostly in CA1 and subiculum. Conclusion: Maximum changes have been seen in E22 and P1 groups. Considering the effect of estrogen on neurogenesis, tamoxifen injection can bring about changes in hippocampal pyramidal cells. The novel finding of this study is the difference in the density of cells at various stages of development. Also, the results show that tamoxifen effects on full-term embryos and one-day newborns are significantly great.