Impairment of spatial learning by estradiol treatment in female mice is attenuated by estradiol exposure during development

Imwalle, D. Bradley; Bateman, Heather L.; Wills, Aileen; Honda, Shin‐ichiro; Harada, Nobuhiro; Rissman, Emilie F.

doi:10.1016/j.yhbeh.2006.06.005

Cited by 13 publications

(7 citation statements)

References 30 publications

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“…Similarly, previously published works show that the ER expression and rate of proliferation in the uterus of animals treated with other estrogenic compounds are significantly lower than in control animals [14,30] and that ER expression in the fetal ovaries of animals treated with butyl paraben are significantly lower than in control animals [28]. On the other hand, maternal adrenal insufficiency or alteration of sensitivity to estrogen has been reported to affect anxiety and learning behaviors [11,31]; therefore, maternal IBP may affect some behaviors, although maternal IBP exposure did not induce hormonal changes in the present study.…”

Section: Discussionsupporting

confidence: 64%

Maternal Isobutyl-Paraben Exposure decreases the Plasma Corticosterone Level in Dams and Sensitivity to Estrogen in Female Offspring Rats

et al. 2009

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ABSTRACT. Isobutyl-paraben (IBP), a widely used preservative in a variety of foods, shows high comparative binding affinity to estrogen receptors. Here, we examined the effects of maternal exposure of rats to IBP on plasma hormone concentrations and organ weights in dams, ratio of male pups, anogenital distance, organ weights and plasma hormone concentrations in offspring, puberty, estrous cycle and response of organ weight and plasma hormone concentrations to estrogen in adult female offspring, and reproductive and adrenal function in adult male offspring, all of which are under developmental estrogen regulation, to clarify the estrogenic effects of IBP during gestation and lactation on the endocrine systems of dams and offspring. While maternal exposure of IBP decreased the plasma corticosterone concentration and increased the uterus weight in dams and increased uterine sensitivity to estrogen in adult female offspring, the other indices examined were largely unaffected by the present treatment. Even though these results indicate little sign of endocrine disrupting effects for IBP, the existence of activity may be a matter of concern due to the possible impact on the health of future generations.KEY WORDS: corticosterone, estrogen, isobutyl-paraben, maternal, rat.J. Vet. Med. Sci. 71(8): 1027-1033, 2009 Parabens have been the most widely used preservatives for more than 50 years in a variety of food, cosmetic and pharmaceutical products [2,4,23] due to their broad spectrum of activity, inertness, low cost and long history of safe use. They have been detected in human urine collected from a demographically diverse group of male and female adults with no known exposure to parabens, suggesting that the majority of people have already been exposed to them [32]. Several studies indicate that exposure to parabens modulates the endocrine system and thus may have harmful consequences on animal and human health [4,7,13,22,28] because of the estrogenic activities of these compounds in vitro and in vivo [7,24], and anti-estrogenic activity in human skin has been shown [22]. In addition, exposure to parabens during adult periods has been implicated in reduction of the male reproductive system in rodents [7,19,20,21], whereas a recent study could not confirm these effects [10]. On the other hand, investigation of the effects of exposure to parabens during gestation to lactation is important because exposure to estrogenic chemicals during development could be a contributory factor in the rising incidence of endocrine dysfunction of offspring later in life [3,5,14,16,26]. But, the effects of early exposure to parabens are not consistent in previous reports [6,13,27,28]. Furthermore, the effects of early exposure to parabens on the endocrine system in adult female offspring, except for vaginal opening and intact uterus weight [13], are unclear. Therefore, we examined the effects of maternal exposure to parabens on several aspects of the endocrine system in male and female offspring, especially the effects on plasma hormone co...

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Section: Discussionsupporting

confidence: 64%

Maternal Isobutyl-Paraben Exposure decreases the Plasma Corticosterone Level in Dams and Sensitivity to Estrogen in Female Offspring Rats

et al. 2009

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“…It is worth noting that the sex differences we found are on the order of 30% which, given the heterogeneity of brain tissue, is remarkable and could represent up to 30% of the epigenome. Our CTX/HIP dissections included many subregions, but the major areas, the hippocampus, cortex and the dentate gyrus, have well documented functions in cognition, many of which are sexually dimorphic and modified by steroid hormones 20,28,29. Moreover, sex differences documented in CTX/HIP include differences in cell numbers, thickness of cortical layers, numbers of spines and electrophysiological properties 24,30.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, sex differences documented in CTX/HIP include differences in cell numbers, thickness of cortical layers, numbers of spines and electrophysiological properties 24,30. Interestingly, the neonatal CTX/HIP contains steroid receptors and steroid synthesizing enzymes,13,23,31,32 and neural structures in CTX/HIP can be modified by not only steroid hormones,20,28,29 but also the environment 9,33,34…”

Section: Discussionmentioning

confidence: 99%

Sex differences in histone modifications in the neonatal mouse brain

Tsai¹,

Grant²,

Rissman³

2009

Epigenetics

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182

140

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Sex differences in neural development are established via a number of cellular processes (i.e., migration, death and survival).One critical factor identified is the neonatal rise in testosterone (T) which activates gene transcription via androgen (AR) and, after aromatization to estradiol, estrogen receptors (ERα and β). Recent evidence shows that AR and ERs interact with histone modifying enzymes. Post-translational modifications of histones, including acetylation and methylation, are involved in transcriptional regulation during normal development. Therefore, we hypothesized that acetylation and/or methylation of histone H3 may underlie sexual differentiation, at least in some regions of the brain. We measured levels of acetylated (H3K9/14Ac) and trimethylated (H3K9Me3) H3 in whole neonatal mouse brains and in three regions: preoptic area + hypothalamus, amygdala and cortex + hippocampus (CTX/HIP). Sex differences in H3K9/14Ac and H3K9Me3 (males > females) were noted in the CTX/HIP on embryonic day 18, the day of birth, and six days later. To determine if T mediates these changes in H3 modifications, pregnant dams received vehicle or T for the final four days of gestation; pup brains were collected at birth. Methylation of H3 was sexually dimorphic despite hormone treatment. In contrast, H3 acetylation in the CTX/HIP of females from T-treated dams rose to levels equivalent to males. Thus, H3 modifications are sexually dimorphic in the developing mouse CTX/HIP and acetylation, but not methylation, is masculinized in females by T in utero. This is the first demonstration that histone modification is associated with neural sexual differentiation.

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“…Over 70% of the basic research articles published in key neuroscience journals in a recent year used only males or did not specify the sex of subjects (Beery and Zucker, 2011), despite overwhelming evidence that there are important differences between male and female brains. Although the most prominent sex differences are often seen for reproductive functions, differences in other realms, such as cognition, energy balance, and stress responsiveness, are also well established (Bangasser and Valentino, 2012; Imwalle et al, 2006; Kimura, 2002; Mauvais-Jarvis, 2015). Moreover, the effects of some manipulations don’t just differ by sex, but may push the brain and behavior in opposite directions in males and females (e.g., Oomen et al, 2009; Shors et al, 2001; Veenema et al, 2013; Waddell et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Cellular and molecular mechanisms of sexual differentiation in the mammalian nervous system

Forger

Strahan

Castillo‐Ruiz

2016

Frontiers in Neuroendocrinology

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Neuroscientists are likely to discover new sex differences in the coming years, spurred by the National Institutes of Health initiative to include both sexes in preclinical studies. This review summarizes the current state of knowledge of the cellular and molecular mechanisms underlying sex differences in the mammalian nervous system, based primarily on work in rodents. Cellular mechanisms examined include neurogenesis, migration, the differentiation of neurochemical and morphological cell phenotype, and cell death. At the molecular level we discuss evolving roles for epigenetics, sex chromosome complement, the immune system, and newly identified cell signaling pathways. We review recent findings on the role of the environment, as well as genome-wide studies with some surprising results, causing us to rethink often-used models of sexual differentiation. We end by pointing to future directions, including an increased awareness of the important contributions of tissues outside of the nervous system to sexual differentiation of the brain.

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Impairment of spatial learning by estradiol treatment in female mice is attenuated by estradiol exposure during development

Cited by 13 publications

References 30 publications

Maternal Isobutyl-Paraben Exposure decreases the Plasma Corticosterone Level in Dams and Sensitivity to Estrogen in Female Offspring Rats

Maternal Isobutyl-Paraben Exposure decreases the Plasma Corticosterone Level in Dams and Sensitivity to Estrogen in Female Offspring Rats

Sex differences in histone modifications in the neonatal mouse brain

Cellular and molecular mechanisms of sexual differentiation in the mammalian nervous system

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