Prenatal antiandrogen treatment simulates prenatal stress consequences on the mesocorticolimbic dopaminergic system development in the male offspring

PALLARÉS ME; PALLARÉS HM; ADROVER E; BAIER CJ ; ANTONELLI MC

Huerta Grande, Cordoba

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigaciones en Neurociencias; 2013

Sociedad Argentina de Investigaciones en Neurociencias

We have previously demonstrated that prenatal stress (PS) impaired midbrain dopaminergic (DA) system metabolism especially after puberty, suggesting a particular sensitivity of DA system to variations in gonadal hormones peaks. We further demonstrated that the reproductive axis of male rats exposed to PS was altered. PS was shown to disrupt perinatal testosterone surges and since DA system could be influenced by androgen exposure, the aim of this research was to evaluate the effect of prenatal administration of the antiandrogen flutamide (FLU) (10 mg/kg daily) to pregnant rats from gestational day 14th to 21st on the DA system development. We found that FLU reduced anogenital distance and induced a two-day delay in the completion of testis descend in the offspring. Malformation of penis, cryptorchidisim and atrophied seminal vesicle were also observed. Morphological studies in mesocorticolimbic DA areas revealed that FLU males presented a decrease on the number of MAP2 immunoreactive neurons in comparison with vehicle treated rats (5% ethanol-propylene glycol) suggesting that prenatal FLU reduced the dendritic arborization of mesencephalic structures, impairing normal connectivity between areas. This research demonstrates that the effects of prenatal androgen manipulation resemble PS impairment of the DA system suggesting that one of the possible mechanisms of action of prenatal insults is related to the alteration of the organizational role of androgens on brain development