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Developmental exposure to low dose estrogenic endocrine disruptors alters sex differences in exploration and emotional behavior in mice.
No full textEstrogenic endocrine disruptors (EEDs) are naturally occurring or man-made compounds present in the environment that are able to bind to estrogen receptors and interfere with normal cellular development in target organs and tissues. There is mounting evidence that EEDs can interfere with the processes of sexual differentiation of brain and behavior in different animal models. We investigated the effects of maternal exposure to EEDs, at concentrations within the range of human exposure and not patently teratogenic, on behavioral responses of male and female house mice (Mus musculus domesticus) before and after puberty. Pregnant dams were trained to spontaneously drink daily doses of corn oil with or without the estrogenic plastic derivative, bisphenol A (BPA 10 microg/kg), or the estrogenic insecticide methoxychlor (MXC 20 microg/kg) from gestation day 11 to postpartum day 8. Their male and female offspring were examined at different ages to examine several components of explorative and emotional behaviors in 3 experimental paradigms: a novelty test before puberty and, as adults, a free-exploratory open-field test and the elevated plus maze test. The main results are sex differences in control mice on a number of behavioral responses at both ages and in all experimental paradigms, while perinatal exposure to BPA or MXC decreased or eliminated such sex differences. The present findings are evidence of long-term consequences of developmental exposure to BPA and MXC on neurobehavioral development and suggest a differential effect of low-dose exposure to these estrogenic chemicals in males and females
Effects of developmental exposure to bisphenol-A on brain and behavior in mice
No full textBisphenol A (BPA) is a widespread estrogenic chemical used in the production of polycarbonate, and epoxy resins lining food and beverage cans and in dental sealants. During fetal life the intrauterine environment is critical for the normal development, and even small changes in the levels of hormones, such as estradiol or estrogen-mimicking chemicals, can lead to changes in brain function and consequently in behavior. We review here a series of ethological studies on the effects of maternal oral exposure during the last part of gestation (prenatal exposure) or from gestation day 11 to postnatal day 7 (perinatal exposure) to a low, environmentally relevant dose of BPA (10 microg/kg bw/day) on behavioral responses of CD-1 mouse offspring. We examined both male and female offspring and found that maternal exposure to BPA affected: (1) behavioral responses to novelty before puberty and, as adults; (2) exploration and activity in a free-exploratory open field; (3) exploration in the elevated plus maze and (4) sensitivity to amphetamine-induced reward in the conditioned place preference test. A consistent effect of the maternal exposure to BPA is that in all these different experimental settings, while a significant sex difference was observed in the control group, exposure to BPA decreased or eliminated the sex difference in behavior. In addition, exposure of female mice to BPA in both adulthood or during fetal life altered subsequent maternal behavior. These findings, together with those from other laboratories, are evidence of long-term consequences of maternal exposure to low-dose BPA at the level of neurobehavioral development
D-amphetamine-related reinforcing effects are reduced in mice exposed prenatally to estrogenic endocrine disrupters
No full textThe effect of bisphenol A on emotional behavior depend upon the timing of exposure, age and gender in mice
No full textAbstract
Experimental evidence suggests that endocrine-disrupting chemicals (EDCs) can permanently disrupt the development of sexually dimorphic behaviors and the structure of sexually dimorphic areas of the brain. EDC exposure has different effects depending on diverse factors, such as the timing and dose of the exposure, the maternal environment and the individual's age and sex. Among EDCs, bisphenol A (BPA) is one of the most studied because of its extensive use, which ranges from dentistry to food/drink packaging. In the present study, we aimed to investigate the behavioral effects of developmental exposure to a low dose of BPA with respect to the timing of the exposure, maternal environment, sex and age at testing. Starting from the last week of pregnancy to the first postpartum week, dams spontaneously drank either corn oil (control group) or a solution containing BPA (10 μg/kg bw/day). At birth, the litters were cross-fostered to different dams to differentiate among the effects of pre- and postnatal exposure. Pre- and postnatally exposed offspring underwent three diverse experimental paradigms for anxiety-related behaviors: as juveniles, a novelty test and at adulthood, both the free exploratory open field and elevated plus maze tests. At both testing ages, pre- and postnatally exposed females showed evidence of increased anxiety and were less prone to explore a novel environment relative to the control females, showing a behavioral profile more similar to control males than females. In this study, the direction of the behavioral changes was affected similarly by the pre- and postnatal exposures, resulting in a disruption of these sexually dimorphic behaviors, although with a greater effect associated with postnatal exposure primarily in females. Our findings indicate that non-reproductive, sexually dimorphic behaviors are sensitive to endocrine disruption during critical developmental periods-particularly the highly critical early neonatal stage. Combined with previous research, our study provides further evidence of the potential risks that even low doses of EDCs may pose to humans, with fetuses and infants being highly vulnerabl
Risk Evaluation of Endocrine-Disrupting Chemicals
Full text linkWe review here our studies on early exposure to low doses of the estrogenic endocrine-disrupting chemical bisphenol A (BPA) on behavior and metabolism in CD-1 mice. Mice were exposed in utero from gestation day (GD) 11 to delivery (prenatal exposure) or via maternal milk from birth to postnatal day 7 (postnatal exposure) to 10 µg/kg body weight/d of BPA or no BPA (controls). Bisphenol A exposure resulted in long-term disruption of sexually dimorphic behaviors. Females exposed to BPA pre- and postnatally showed increased anxiety and behavioral profiles similar to control males. We also evaluated metabolic effects in prenatally exposed adult male offspring of dams fed (from GD 9 to 18) with BPA at doses ranging from 5 to 50 000 µg/kg/d. The males showed an age-related significant change in a number of metabolic indexes ranging from food intake to glucose regulation at BPA doses below the no observed adverse effect level (5000 µg/kg/d). Consistent with prior findings, low but not high BPA doses produced significant effects for many outcomes. These findings provide further evidence of the potential risks that developmental exposure to low doses of the endocrine disrupter BPA may pose to human health, with fetuses and infants being highly vulnerable
Prenatal exposure of mice to an environmental estrogen alters sex differences in brain and behavior
No full text56. PRENATAL EXPOSURE OF MICE TO A LOW-DOSE
ENVIRONMENTAL ESTROGEN ALTERS SEX DIFFERENCES IN
BRAIN AND BEHAVIOR. Palanza; P:; Ponzi, D., Gioiosa, L., Flugge, G.,
Parmigiani, S., and Fuchs, E. Dipartimento di Biologia Evolutiva,
Universita` di Parma. Laboratory of Neurobiology, German Primate
Center, Goettingen.
The presence in the environment to a large number of environmental
and industrial compounds that have estrogenic activity (Environmental
Estrogens, EE) raises major health concerns. Sexually dimorphic behaviors
are particularly useful to study the effects of low concentrations of EE,
similar to environmental contamination, because they are highly sensitive to
alterations of the endocrine mileu. Behavior is the endpoint of complex,
integrated systems and therefore is a good biomarker of neuroendocrine and
neurobiological alterations. We investigated the effects of prenatal exposure
(via maternal treatment) to an environmental-like, low dose of bisphenol A
(BPA, an estrogenic compound used in food industry) on mice behavioral
response to novelty and on the noradrenergic system in the brain. Mice
were tested in a free-choice novelty preference test at adolescence, in a freeexploratory
open field and elevated plus-maze (EPM) as adults. Both
adolescent and adult mice exposed to BPAshowed either a decrease or a
reversion in sexual differences in response to novelty. Contrary to the
control profile, BPA-exposed males and females did not differ in exploration,
an effect due mainly to changes in BPA-exposed females relative to
controls. As adults, mice were sacrificed and their brain were analyzed for
alpha2 adrenergic receptor system in locus coeruleus (LC) and preoptic area
(PO). Control mice showed a sexually dimorphic profile of receptor density
in the PO, while prenatal BPA-exposure lowered such sex differences;
BPA-exposed males showed increased receptors number, thus resulting
more similar to the control females’ profile. In both the PO and LC of
exposed animals, a decreased affinity of alpha2-adrenergic receptors was
observed
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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