Neonatal genistein or bisphenol-A exposure alters sexual differentiation of the AVPV☆

Patisaul, Heather B.; Fortino, Anne E.; Polston, Eva K.

doi:10.1016/j.ntt.2005.11.004

Cited by 178 publications

(131 citation statements)

References 40 publications

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“…One of the most striking neurobiological effects of BPA is the loss of sexual dimorphism in brain structure and behavior illustrated by animal studies (4,(28)(29)(30)(31), findings concordant with human epidemiological studies (5-7). The molecular mechanisms underlying BPA-induced disruption of sexually dimorphic phenotypes are not understood.…”

Section: Discussionsupporting

confidence: 61%

Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure

Kundaković

Gudsnuk

Franks

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

434

390

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Bisphenol A (BPA) is an estrogenic endocrine disruptor widely used in the production of plastics. Increasing evidence indicates that in utero BPA exposure affects sexual differentiation and behavior; however, the mechanisms underlying these effects are unknown. We hypothesized that BPA may disrupt epigenetic programming of gene expression in the brain. Here, we provide evidence that maternal exposure during pregnancy to environmentally relevant doses of BPA (2, 20, and 200 μg/kg/d) in mice induces sex-specific, dose-dependent (linear and curvilinear), and brain region-specific changes in expression of genes encoding estrogen receptors (ERs; ERα and ERβ) and estrogen-related receptor-γ in juvenile offspring. Concomitantly, BPA altered mRNA levels of epigenetic regulators DNA methyltransferase (DNMT) 1 and DNMT3A in the juvenile cortex and hypothalamus, paralleling changes in estrogen-related receptors. Importantly, changes in ERα and DNMT expression in the cortex (males) and hypothalamus (females) were associated with DNA methylation changes in the ERα gene. BPA exposure induced persistent, largely sex-specific effects on social and anxiety-like behavior, leading to disruption of sexually dimorphic behaviors. Although postnatal maternal care was altered in mothers treated with BPA during pregnancy, the effects of in utero BPA were not found to be mediated by maternal care. However, our data suggest that increased maternal care may partially attenuate the effects of in utero BPA on DNA methylation. Overall, we demonstrate that low-dose prenatal BPA exposure induces lasting epigenetic disruption in the brain that possibly underlie enduring effects of BPA on brain function and behavior, especially regarding sexually dimorphic phenotypes.environmental | fetal origin of adult disease

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Section: Discussionsupporting

confidence: 61%

Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure

Kundaković

Gudsnuk

Franks

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

434

390

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“…Early postnatal exposure of rat pups to genistein or bisphenol A decreased both the number and the percentage of cells in the AVPV that coexpressed tyrosine hydroxylase (an enzyme involved in dopamine synthesis) and ERα in the AVPV of female rats; this effect was seen just for number (not percentage) of double-labeled cells in males, suggesting that female rats are more sensitive to this early EDC exposure [113]. Similar results were reported in mice by Rubin et al [130], who showed that the sex difference in AVPV size, and tyrosine hydroxylase expression in the AVPV, were diminished by prenatal bisphenol A, primarily due to effects in the females.…”

Section: Effects Of Perinatal Edcs On the Avpv And Sdn-poa Morphologymentioning

confidence: 98%

“…Several recent studies have demonstrated direct effects of endocrine disruptors on hypothalamic neural circuitry, hypothalamic morphology, the phenotype of hypothalamic cells, and expression of steroid hormone receptors [141,115,134,113]. For illustrative purposes, the AVPV and SDN-POA will again be the focus of discussion, as the morphology of brain regions are particularly well studied in the endocrine disruption field.…”

Section: Morphological Effects Of Fetal Endocrine-disrupting Chemicalmentioning

confidence: 99%

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Gore¹

2008

Frontiers in Neuroendocrinology

230

122

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The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted.

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“…PCBs may have variable degrees of impact depending on which congeners or congener mixtures are involved, the organism's age at exposure, the sex of the individual, the degree of exposure and the availability of compensatory diet or social buffering to counteract those effects. An accurate evaluation of ecologically relevant xenobiotic exposure (Battershill, 1994;Brouwer et al, 1999).The neuroendocrine system serves as an interface between the central nervous system and peripheral endocrine organs, and thus represents a prime target for endocrine disruption by PCBs (Patisaul et al, 2006). PCBs and their metabolites can act at multiple nodes of the neuroendocrine axis: they may serve as hormone mimics (Connor et al, 1997), alter circulating hormone levels (Desaulniers et al, 1999), change patterns of estrous cyclicity (Meerts et al, 2004;Buitenhuis et al, 2004), disrupt hormone metabolism Kester et al, 2000;Yamane et al, 1975), influence endocrine-related and hypothalamic gene expression (Aluru et al, 2004;Bansal et al, 2005;Colciago et al, 2005;Flouriot et al, 1995;Gore et al, 2002;Pravettoni et al, 2005;Salama et al, 2003), interfere with hormone binding proteins (Brouwer and van den Berg, 1986;Chauhan et al, 2000), alter neuronal signaling to endocrine regions of the brain (Khan and Thomas, 2001;Morse et al, 1996;Seegal et al, 1985;Seegal et al, 1990) or indirectly affect steroid receptor availability via molecular crosstalk (Brunnberg et al, 2003;Pearce et al, 2004).…”

mentioning

confidence: 99%

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

Steinberg

Juenger

Gore

2007

Hormones and Behavior

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Polychlorinated biphenyls (PCBs) are a family of toxicants that persist in measurable quantities in human and wildlife tissues, despite their ban in production in 1977. Some PCB mixtures can act as endocrine disrupting chemicals (EDCs) by mimicking or antagonizing the actions of hormones in the brain and periphery. When exposure to hormonally active substances such as PCBs occurs during vulnerable developmental periods, particularly prenatally or in early postnatal life, they can disrupt sex-specific patterning of the brain, inducing permanent changes that can later be manifested as improper sexual behaviors. Here, we investigated the effects of prenatal exposure to the PCB mixture Aroclor (A) 1221 on adult female reproductive behaviors in a dose-response model in the SpragueDawley rat. Using a paced mating paradigm that permits the female to set the timing of mating and control contact with the male during copulation, we were able to uncover significant differences in female-typical sexual activities in A1221-exposed females. Specifically, A1221 causes significant effects on mating trial pacing, vocalizations, ambulation and the female's likelihood to mate. The results further demonstrate that the intermediate treatment group has the greatest number of disrupted endpoints, suggestive of non-linear dose responses to A1221. These data demonstrate that the behavioral phenotype in adulthood is disrupted by low, ecologically relevant exposures to PCBs, and the results have implications for reproductive success and health in wildlife and women. KeywordsAroclor 1221; Paced mating; PCB; Female reproductive behavior; Endocrine disruption Polychlorinated biphenyls (PCBs) were used in industry as inflammable coolants and lubricants and as components of paints and plastics. Banned in 1977 in response to dawning public awareness of their estrogenic and potentially toxic effects on humans and wildlife, PCBs continue to leach into soil, air and groundwater via retired industrial equipment, and from old factories and buildings. PCBs may have variable degrees of impact depending on which congeners or congener mixtures are involved, the organism's age at exposure, the sex of the individual, the degree of exposure and the availability of compensatory diet or social buffering to counteract those effects. An accurate evaluation of ecologically relevant xenobiotic exposure (Battershill, 1994;Brouwer et al., 1999).The neuroendocrine system serves as an interface between the central nervous system and peripheral endocrine organs, and thus represents a prime target for endocrine disruption by PCBs (Patisaul et al., 2006). PCBs and their metabolites can act at multiple nodes of the neuroendocrine axis: they may serve as hormone mimics (Connor et al., 1997), alter circulating hormone levels (Desaulniers et al., 1999), change patterns of estrous cyclicity (Meerts et al., 2004;Buitenhuis et al., 2004), disrupt hormone metabolism Kester et al., 2000;Yamane et al., 1975), influence endocrine-related and hypothalamic gene expression ...

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Neonatal genistein or bisphenol-A exposure alters sexual differentiation of the AVPV☆

Cited by 178 publications

References 40 publications

Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure

Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

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