Sexual dimorphism, brain development

Can we expect environmental endocrine disruptors to affect the sexual development of the human fetus In my opinion, the answer is an absolute yes, if only because we know that endocrine disruptors act like foreign hormones and thereby disrupt natural hormone physiology. Hormones are critical in fetal sexual and brain development. Exposure of the fetus to hormones can produce profound changes in development. In the case of androgenic hormones, for example, exposure diverts a genetic female to take on the phenotypic appearance of a male, and these hormones change the areas of the brain that ordinarily differ between the sexes (sexually dimorphic areas). 

Most developmental neurotoxicity studies have focused on general impairment of behaviour, but some studies have also found evidence for effects on sexual dimorphic behaviour. Hormones play a central role in central nervous system development, including the sexual differentiation of the brain. Studies on hormones and various endocrine disrupting chemicals (particularly those with estrogenic or antiandrogenic effects) have shown that the developing brain may be susceptible to disturbances in sexual behaviour. Therefore, effects on one sex but not the other should not be dismissed, but must be evaluated in the context of effects on sexual differentiation of the brain. 

In brain development, 5-HT, like DA, exerts a trophic action, by a reciprocal interaction with other neurotransmitters, in specific development processes (Pares-Herbute et al. 1989). Some studies have reported changes in 5-HT development in rats perinatally exposed to A -THC. Thus, this cannabinoid produced a decrease in 5-HT content in diencephalic areas but not in other brain areas (Molina-Holgado et al. 1996). When animals perinatally exposed toA -THC matured, they exhibited an increased 5-HT activity/metabolism in the hypothalamus, neostriatum, hippocampus, septum nuclei, and midbrain raphe nuclei. Some of these effects were only seen in males, indicating a sexually dimorphic response (Molina-Holgado et al. 1997). 

The Extreme Male Brain theory, in fact, argues that prenatal testosterone exposure is a strong candidate for contributing to sexual dimorphism in human behaviour, including social development, and may represent a risk factor for conditions characterized by social impairments, particularly autism spectrum conditions (reviewed in Knickmeyer and Baron-Cohen, 2006). 

Giedd JN, Castellanos FX, Rajapakse JC, Vaituzis AC, Rapoport JL (1997) Sexual dimorphism of the developing human brain. Prog. Neuro-Psychopharmacol Biol Psych 21 1185-1201. 

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