INVESTIGADORES
BAIER Carlos Javier
artículos
Título:
Maternal administration of flutamide during late gestation affects the brain and reproductive organs development in the rat male offspring
Autor/es:
PALLARÉS M.E.; ADROVER E.; IMSEM M.; GONZÁLEZ D.; FABRE B.; MESCH V.; BAIER C.J.; ANTONELLI M.C.
Revista:
NEUROSCIENCE
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2014 vol. 278 p. 122 - 135
ISSN:
0306-4522
Resumen:
We have previously demonstrated that male rats exposed to stress during
the last week of gestation present age-specific impairments of brain
development. Since the organization of the fetal developing brain is
subject to androgen exposure and prenatal stress was reported to disrupt
perinatal testosterone surges, the aim of this research was to explore
whether abnormal androgen concentrations during late gestation affects
the morphology of the prefrontal cortex (PFC), hippocampus (HPC) and
ventral tegmental area (VTA), three major areas that were shown to be
affected by prenatal stress in our previous studies. We administered
10-mg/kg/day of the androgen receptor antagonist flutamide
(4'nitro-3'-trifluoromethylsobutyranilide) or vehicle injections to
pregnant rats from days 15-21 of gestation. The antiandrogenic effects
of flutamide were confirmed by the analysis of androgen-dependent
developmental markers: flutamide-exposed rats showed reduced anogenital
distance, delay in the completion of testis descent, hypospadias,
cryptorchidism and atrophied seminal vesicles. Brain morphological
studies revealed that prenatal flutamide decreased the number of MAP2 (a
microtubule-associated protein type 2, present almost exclusively in
dendrites) immunoreactive neuronal processes in all evaluated brain
areas, both in prepubertal and adult offspring, suggesting that prenatal
androgen disruption induces long-term reductions of the dendritic
arborization of several brain structures, affecting the normal
connectivity between areas. Moreover, the number of tyrosine hydroxylase
(TH)-immunopositive neurons in the VTA of prepubertal offspring was
reduced in flutamide rats but reach normal values at adulthood. Our
results demonstrate that the effects of prenatal flutamide on the
offspring brain morphology resemble several prenatal stress effects
suggesting that the mechanism of action of prenatal stress might be
related to the impairment of the organizational role of androgens on
brain development.