Effects of pre- and neonatal exposure to bisphenol A on murine brain development

Tando, So; Itoh, Kyoko; Yaoi, Takeshi; Ikeda, Jun; Fujiwara, Yasuhiro; Fushiki, Shinji

doi:10.1016/j.braindev.2006.10.003

Cited by 58 publications

(35 citation statements)

References 23 publications

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“…We consider that the estrogenic effect of BPA is caused by its binding to estrogen receptor α because no significantly increased luciferase activity was observed when the expression plasmid pGLrERα was omitted from plasmids transfected to PC12 cells (data not shown). On the other hand, a previous study has reported that fetal neonatal exposure to BPA has effects on brain development in mice [61]. We further found in our current study that TBT induces ER stress-associated apoptosis in cultured PC12 cells by upregulating the Bcl-2 family protein Bim (Figure 4(c)).…”

Section: Discussionsupporting

confidence: 80%

Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells

Sasaya¹,

Yasuzumi²,

Maruoka³

et al. 2012

ABC

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Endocrine-disrupting chemicals (EDCs) are known to exert estrogen-like effects that are similar to those made by naturally produced hormones or by inhibition of the receptors in the cell receiving the hormones. Recently, several reports have indicated that EDCs can affect the developing central nervous system. In our current study, we report that some EDCs induce apoptosis in cultured PC12 cells and can be classified into three groups. Bisphenol A (BPA), pnonylphenol (NP) and tributyltin chloride (TBT) were found to induce endoplasmic reticulum (ER) stress-associated apoptosis and activate the unfolded protein response (UPR) system, whereas benomyl (beno) induced non-ER stress-associated apoptosis. The half-maximal apoptosis-inducing concentrations (IC 50 ) of these EDCs were 160 µM for BPA, 25.6 µM for NP, 640 nM for TBT and 48 µM for beno. Although these concentrations are higher than those found in the environment, some EDCs may have apoptotic effects on various cells in the body, including neurons, through their accumulation in the body over time or condensation through the food chain. On the other hand, benzopyrene, fenvalerate, styrene monomer and bis(2-ethylhexyl)phthalate did not induce apoptosis in PC12 cells. We analyzed also whether apoptosis-inducing EDCs had an estrogen-like effect on cultured PC12 cells transfected with a luciferase reporter plasmid, the activity of which is dependent on estrogen receptor α. We found that BPA had an estrogen-like effect (EC 50 = 5.9 µM) but that NP, TBT and beno did not in transfected PC12 cells. These results suggest that BPA may predominantly exert estrogenic effects, but others may predominantly have apoptosis-inducing effects on cells in the body exposed to a polluted environment.

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Section: Discussionsupporting

confidence: 80%

Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells

Sasaya¹,

Yasuzumi²,

Maruoka³

et al. 2012

ABC

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“…There have been many published in vivo and in vitro mechanistic studies providing examples of effects of BPA that are observed at a lower dose, but are not observed at a higher dose [2]. Such a nonmonotonic dosageresponse relationship to endocrine disrupters is currently proposed [27]. In the present study, BPA markedly decreased the concentration of NMDAR subunits in a different degree and a different pattern during developmental period.…”

Section: Discussionmentioning

confidence: 63%

Perinatal exposure to bisphenol‐A changes N‐methyl‐D‐aspartate receptor expression in the hippocampus of male rat offspring

Wang

Zhang

et al. 2009

Enviro Toxic and Chemistry

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Bisphenol-A (BPA) is one of the most common environmental endocrine disrupters with mixed estrogen agonist/antagonist properties. The toxicity of BPA has been extensively evaluated in a variety of tests in rodents, including developmental and reproductive toxicity, and carcinogenicity. The objective of the present study is to evaluate whether or not perinatal maternal exposure to BPA at 0.05, 0.5, 5, 50, and 200 mg/kg/d affects N-methyl-D-aspartate (NMDA) receptor (NMDAR) subunits NR1, NR2A, 2B, estrogen receptor beta (ERbeta), and aromatase cytochrome P450 (P450arom) protein expressions of hippocampus in male rat offspring during postnatal development. Western-blotting analyses showed that perinatal exposure to BPA significantly affected the expression of NMDAR subunits. At the lower doses of 0.05 to 50 mg/kg/d, BPA concentration dependently inhibited the expression of NMDAR subunits. However, at the higher dose (200 mg/kg/d), the effects of BPA on these subunits were different, with a stronger inhibition of NR1 expression and a slighter inhibition of NR2A, 2B expression when compared with those at the lower dosage of BPA. In addition, perinatal exposure to BPA inhibited the expression of ERbeta protein, but increased P450arom protein expression in a concentration-dependent manner, especially during the early postnatal period (the first 1-3 postnatal weeks). No significant influence of BPA on P450arom was observed at postnatal week 8. These data suggest that environmental BPA exposure may affect the development of the brain, enhancing the local biosynthesis of estrogen in the brain, inhibiting ERbeta and NMDAR expressions.

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“…The rationale for using this strain in this study is, although several other reports have shown the data related to both female and male midbrain DA nuclei by using strains CBA/J [24], BALB/c [19], C57BL/6J [17], and ddY [35], there is little information about C3H mice, which are extensively used as experimental animals. The profiles in this study could provide a framework for further investigations of the C3H mouse midbrain.…”

Section: Discussionmentioning

confidence: 99%

Morphological Analyses of Sex Differences and Age-Related Changes in C3H Mouse Midbrain

Tanida

Warita

Mitsuhashi

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. While it is commonly hypothesized that sexual differentiation in the mammalian brain is initiated mainly by gonadal sex steroids, recent evidence has suggested that dopaminergic (DA) neurons within the rodent midbrain have sex differences independent of gonadal secretions. More recently, it has been reported that Sry (the sex-determining region of the Y chromosome) is directly involved in this difference. The possibility of sexual dimorphism in the mouse midbrain needs to be elucidated. In the present study, the midbrain of C3H mice, which is little understood, was investigated histologically and immuno-histoplanimetrically to reveal sexual and developmental differences. The female ventral tegmental area appeared to contain higher immunoreactivity to tyrosine hydroxylase (TH) than that of males at 11 weeks of age, whereas general histological differences between the sexes were not clearly found. The THimmunoreactive (TH-ir) neurons within the A8, A9, and A10 mesencephalic areas were examined separately. There was the sex difference in the time period when TH-ir cell numbers significantly increased, indicating that the growth rate of midbrain DA nuclei also differs and that the midbrain DA system may trace different processes of sexual maturation between the sexes. These differences between female and male may reflect the direct regulation by Sry or the multiple effects of both Sry and sex steroids. Further experiments are needed to determine which factor forms this difference in the growth pattern in the numbers of TH-ir neurons.KEY WORDS: age-related change, dopaminergic (DA) neuron, midbrain, sex difference, tyrosine hydroxylase (TH).J. Vet. Med. Sci. 71 (7): [855][856][857][858][859][860][861][862][863] 2009 Sex differentiation of the mammalian brain is influenced mainly by perinatal testicular steroid hormones [25]. In males, androgen (or its metabolite estrogen) initiates a program of male-specific development in many brain regions. In females, on the other hand, neural development traces female-specific processes caused by a low level of gonadal steroid hormone. These mechanisms result in morphological sexual dimorphism, which controls sexually dimorphic behaviors and functions [16]. Sex steroid hormones are associated with the constitution of several sexual dimorphisms via estrogen receptor (ER) [22]. Moreover, the sexual differentiation of dopaminergic (DA) neurons within the preoptic region of the diencephalon depends on ER [32].However, other sex differentiation processes have been found to depend on the sex chromosomal gene directly rather than on gonadal steroid hormones in the midbrain. T h e c e l l c u l t u r e s d i s s o c i a t e d f r o m f e m a l e r a t mesencephalon on embryonic day 14 (ED 14; before exposure to the gonadal steroid hormone shower) contain higher numbers of DA neurons than male cultures, and hormonal treatment does not erase this differentiation [4]. The sex-determining region of the Y chromosome (Sry) is transcribed in the hypothalamus, mesencephalon, and tes...

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Effects of pre- and neonatal exposure to bisphenol A on murine brain development

Cited by 58 publications

References 23 publications

Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells

Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells

Perinatal exposure to bisphenol‐A changes N‐methyl‐D‐aspartate receptor expression in the hippocampus of male rat offspring

Morphological Analyses of Sex Differences and Age-Related Changes in C3H Mouse Midbrain

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