Prenatal Aroclor 1254 exposure and brain sexual differentiation: Effect on the expression of testosterone metabolizing enzymes and androgen receptors in the hypothalamus of male and female rats

Colciago, Alessandra; Negri‐Cesi, P.; Pravettoni, A.; Mornati, O.; Casati, Lavinia; Celotti, F.

doi:10.1016/j.reprotox.2006.07.002

Cited by 44 publications

(25 citation statements)

References 47 publications

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“…PCBs can also affect the expression level of estrogen and androgen receptors. Pre-and perinatal exposure to Aroclor 1221 increased neural estrogen receptor expression (95) and recently prenatal exposure to Aroclor 1254 was shown to affect the expression of testosterone metabolizing enzymes and androgen receptors in rat brain (96). Given the fact that estrogens and androgens are involved in several aspects of brain development and also promote processes such as dendritic growth, spinogenesis and synaptogenesis (24,(97)(98)(99)(100), it is likely that this endocrine disrupting effect of PCBs also affects cerebellar development and brain development in general.…”

Section: Neurodevelopmental Effects Of Pcbsmentioning

confidence: 98%

Endocrine disrupting polyhalogenated organic pollutants interfere with thyroid hormone signalling in the developing brain

Darras¹

2008

Cerebellum

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Persistent polyhalogenated organic pollutants are present worldwide and accumulate along the food chain. They interfere with human and animal health and are particularly harmful for pre- and perinatal neurodevelopment. The mechanisms behind the observed effects vary depending on the specific compound investigated. Co-planar polychlorinated biphenyls (PCBs) can act via the arylhydrocarbon receptor while many ortho-substituted PCBs disrupt intracellular Ca(2+) homeostasis. A common mechanism for a wide variety of PCBs is interference with thyroid hormone (TH) signalling in developing brain, by changing intracellular TH availability or by interacting directly at the level of the TH receptors. Studies on gene expression in cortex and cerebellum revealed both hypothyroid- and hyperthyroid-like effects. However, since THdependent gene expression plays a crucial role in the coordination of neuronal proliferation, migration, synaptogenesis, myelination, etc., both reduced/delayed and increased/premature expression may result in permanent structural changes in neuronal communication networks, leading to lifelong deficits in cognitive performance, motor functions, and psychobehavior. In a similar way, PCBs are able to interfere with estrogen- and androgen-dependent brain development and in some studies neurobehavioral outcome was shown to be gender-specific. Other persistent organohalogens like polychlorinated dibenzo-p-dioxins (PCDDs) and polybrominated diphenyl ethers (PBDEs) also act as endocrine disrupters in the developing brain. Several of the mechanisms involved are similar to those of PCBs, but each group also works via own specific pathways. The fact that persistent organohalogens can amplify the neurotoxic effects of other environmental pollutants, such as heavy metals, further increases their risk for human and animal neurodevelopment.

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Section: Neurodevelopmental Effects Of Pcbsmentioning

confidence: 98%

Endocrine disrupting polyhalogenated organic pollutants interfere with thyroid hormone signalling in the developing brain

Darras¹

2008

Cerebellum

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“…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. Prenatal treatment of pregnant dams from days 15-19 of gestation with the PCB mixture Aroclor 1254 resulted in higher mRNA levels of 5-alpha reductase mRNA (the enzyme that converts testosterone to dihydrotestosterone), and lower levels of androgen receptor mRNA, in the hypothalamus of female but not male embryos on gestational day 20 [33]. This same laboratory also showed that prenatal Aroclor 1254 stimulated levels of arylhydrocarbon receptor (AhR) protein in hypothalamus of male but not female rats [118].…”

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

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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“…A study by Colciago et al [23] found that acute treatment with Aroclor 1254 (A1254) during embryonic development results in decreased AR protein expression in the hypothalamus of female rats at E20. In vitro experiments in this same study suggest that the activity of 5-α reductase, the enzyme that converts testosterone into the more potent androgen, dihydrotestosterone, may be increased in females.…”

Section: Nuclear Receptor Gene Expression [Ar Aryl Hydrocarbon Recepmentioning

confidence: 99%

Estrogenic environmental endocrine-disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle

Dickerson

Gore

2007

Rev Endocr Metab Disord

190

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Endocrine disrupting chemicals (EDCs) are natural or synthetic compounds that interfere with the normal function of an organism's endocrine system. Many EDCs are resistant to biodegradation, due to their structural stability, and persist in the environment. The focus of this review is on natural and artificial EDCs that act through estrogenic mechanisms to affect reproductive neuroendocrine systems. This endocrine axis comprises the hypothalamic gonadotropin-releasing hormone (GnRH), pituitary gonadotropins, and gonadal steroid hormones, including estrogens. Although it is not surprising that EDCs that mimic or antagonize estrogen receptors may exert actions upon reproductive targets, the mechanisms for these effects are complex and involve all three levels of the hypothalamic-pituitary-gonadal (HPG) system. Nevertheless, considerable evidence links exposure to estrogenic environmental EDCs with neuroendocrine reproductive deficits in wildlife and in humans. The effects of an EDC are variable across the life cycle of an animal, and are particularly potent when exposure occurs during fetal and early postnatal development. As a consequence, abnormal sexual differentiation, disrupted reproductive function, or inappropriate sexual behavior may be detected later in life. This review will cover the effects of two representative classes of estrogenic EDCs, phytoestrogens and polychlorinated biphenyls (PCBs), on neuroendocrine reproductive function, from molecules to behavior, across the vertebrate life cycle. Finally, we identify the gaps of knowledge in this field and suggest future directions for study.

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Prenatal Aroclor 1254 exposure and brain sexual differentiation: Effect on the expression of testosterone metabolizing enzymes and androgen receptors in the hypothalamus of male and female rats

Cited by 44 publications

References 47 publications

Endocrine disrupting polyhalogenated organic pollutants interfere with thyroid hormone signalling in the developing brain

Endocrine disrupting polyhalogenated organic pollutants interfere with thyroid hormone signalling in the developing brain

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Estrogenic environmental endocrine-disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle

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