Abstract
During perinatal life, sex steroids, such as estradiol, have marked effects on the development and function of the nervous system. Environmental estrogens or xenoestrogens are man-made chemicals, which animal and human population encounter in the environment and which are able to disrupt the functioning of the endocrine system. Scientific interest in the effects of exposure to xenoestrogens has focused more on fertility and reproductive behaviors, while the effects on cognitive behaviors have received less attention. Therefore, the present study explored whether the organochlorine insecticide Methoxychlor (MXC), with known xenoestrogens properties, administered during the perinatal period (from gestational day 11 to postnatal day 8) to pregnant-lactating females, at an environmentally relevant dose (20 µg/kg (body weight)/day), would also affect learning and memory functions depending on the hippocampus of male and female offspring mice in adulthood. When tested in adulthood, MXC perinatal exposure led to an increase in anxiety-like behavior and in short-term spatial working memory in both sexes. Emotional learning was also assessed using a contextual fear paradigm and MXC treated male and female mice showed an enhanced freezing behavior compared to controls. These results were correlated with an increased survival of adult generated cells in the adult hippocampus. In conclusion, our results show that perinatal exposure to an environmentally relevant dose of MXC has an organizational effect on hippocampus-dependent memory and emotional behaviors.
Highlights
During perinatal life, sex steroids, such as estradiol, have marked effects on the development of the neuroendocrine system and the expression of related behaviors
ELEVATED PLUS-MAZE (EPM) A two-way analyses of variance (ANOVA) on the percentage of time spent in the open arm revealed a significant effect of the treatment (F(1,46) = 17.690, p < 0.001), but no effect of sex (F(1,46) = 0.107, p = 0.745) or interaction between sex and treatment (F(1,46) = 0.126, p = 0.724)
Both male and female mice perinatally exposed to MXC exhibited a significant increase in anxiety-like behavior evaluated in the elevated plus-maze (EPM) compared to control animals, since the percentage of time spent in the open arms was lower compared to control groups (Figure 1 )
Summary
Sex steroids, such as estradiol, have marked effects on the development of the neuroendocrine system and the expression of related behaviors. The classical theory of brain sexual differentiation holds that endogenous steroid hormones, during critical periods of development, organize sexual dimorphisms in brain neuronal circuits; these effects are classified as “organizational effect”. Endogenous steroid hormones act on these sexually dimorphic neural circuits to give rise to sex differences in behavioral responses (which are classified as “activational effects”). A variety of man-made chemicals, which animal and human population encounter daily in their environment, are able to disrupt the functioning of the endocrine system Certain of these artificial environmental contaminants are called “xenoestrogens”, since they mimic the action of naturally produced estrogens (for recent reviews see Frye et al, 2012; Fisher, 2004).
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