Genistein is a phytoestrogen, produced by Leguminosae, largely present in human and laboratory animal diets, sharing structural features with the 17beta-estradiol, so it can bind estrogen receptors, exerting both estrogenic and antiestrogenic activity. Genistein is present in soy based infant formulas widely used in many countries. Phytoestrogens are considered to have beneficial effects on adults, but little is known about the effects of massive neonatal exposure, that could cause long-term neurological alterations. To test this hypothesis we orally administered to CD1 male and female mice from postnatal day 1 (PD1) to PD8: genistein (50 mg/kg in sesame oil), estradiol ( 50μg/kg in sesame oil) or only vehicle. Mice were tested at PD60, sacrificed, and acrolein-fixed for neurohistological investigations. To test the anxiety behavior, we used the Elevated Plus Maze (EPM) and the Open Field (OF). Mice activity on EPM was recorded during a 5 min trial, considering the number of entries and the time spent into open arms. No significant effect of treatment or gender was observed. For the OF test, we recorded the distance covered and the time spent in center area versus the peripheral area during a 10 min test. Here we observed a significant effect of both gender and treatment. Control males spent more time and cover a longer distance in the center area than females. Genistein-exposed females show a significant increase of the time spent and distance covered in the center area, whereas genistein-treated males have a significant decrease of the two parameters. We are currently investigating putative alterations of the nitrergic and the vasopressin systems. Perinatal exposure to genistein has therefore an anxiolitic effect in females and an anxiogenic effect in males. This research was supported by Compagnia di San Paolo (Progetto Neuroscienze). PhD student fellowship of ARG is partly supported by Compagnia di San Paolo.
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