Anxiety is one of the most frequent psychiatric disorders. Despite the fact that most studies describe an anxiolytic effect of testosterone, hyperandrogenemia in mothers is assumed to be related to an increased risk of mood disorders in their offspring. An increasing body of scientific evidence suggests that an altered expression of interneuronal markers of the hippocampus may be the cause of anxiety. The aim of this study was to examine the influence of maternal hyperandrogenemia on behavioral parameters of anxiety-like behavior, neuropeptide Y (NPY) and parvalbumin (PV) expression in the hippocampus, and the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex. Pregnant female Wistar albino rats were treated with testosterone undecanoate on the 20th day of gestation. Anxiety-like behavior in adult female offspring was evaluated by the elevated plus maze test and the open field. The number of PV and NPY immunoreactive cells in the hippocampus was determined immunohistochemically. The level of BDNF expression in the hippocampus and cerebral cortex was analyzed with the Western blot test. Prenatal hyperandrogenization increased anxiety-like behavior in female offspring and decreased expression of NPY+ and PV+ in the CA1 region of the hippocampus as compared to the control group. BDNF expression in the hippocampus and cerebral cortex of prenatally androgenized female offspring was significantly increased in comparison with the controls. Prenatal hyperandrogenization may be the cause of anxiety-like behavior in female offspring. Decrease in NPY and PV expression in the hippocampus may explain the possible mechanism of hyperandrogenization induced anxiety.

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The structure of heterochromatin protects genome from undesirable recombinations, while estrogen and luteinizing-releasing hormone (LHRH) cause changes in structure of chromatin. The objective of this study was to prove the connection of neonatally applied estrogen and LHRH, with shown effects on chromatin in hippocampus of adult male rats. Stereological results have shown that total surface of neuron area in estrogen treated animals significantly reduced in regard to the control group as well as groups treated with LHRH. The number of heterochromatin granules in either estrogen or LHRH treated groups significantly increased, while in the last fourth group treated with both estrogen and LHRH the difference is even more expressed, both in regard to the control group and other groups. [Projekat Ministarstva nauke Republike Srbije, br. 173034]