Early regulation of brain aromatase (<i>cyp19a1b</i>) by estrogen receptors during zebrafish development

Mouriec, Karen; Lareyre, Jean‐Jacques; Tong, Sok-Keng; Page, Yann Le; Vaillant, Colette; Pellegrini, Elisabeth; Pakdel, Farzad; Chung, Bon Chu; Kah, Olivier; Anglade, Isabelle

doi:10.1002/dvdy.22069

Cited by 83 publications

(91 citation statements)

References 68 publications

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“…This finding was confirmed in several teleost fishes including the Atlantic salmon, Salmo salar [19], stickleback (Gasterosteus aculeatus) [20], African catfish (Clarias gariepinus) [21], European sea bass (Dicentrarchus labrax) [16] and peacock blenny (Salaria pavo) [22]. This high neural aromatase activity has been attributed to the high levels of neurogenesis present in the teleosts brain compared to mammals [7,13,15]. Moreover, estrogen is an important neurotrophic factor, playing this role throughout life and influencing neuronal differentiation [23,24], participating in the process of embryonic and adult neurogenesis [25,26].…”

Section: Introductionmentioning

confidence: 51%

“…The quality and concentration of RNA were assessed by spectrophotometry and checked by running an aliquot (1 g) on a 1.8% agarose-formaldehyde gel. The cDNAs were synthesized from 1 g of total RNA using Superscript II (Invitrogen; Carlsbad, CA) and oligo (dT) [12][13][14][15][16][17][18] primers in a 20 l reaction volume with incubation at 42 • C for 60 min, 37 • C for 15 min, and 70 • C for 15 min and cDNAs were then stored at −80 • C until use.…”

Section: Rna Extraction Cdna Library Construction and Molecular Clonmentioning

confidence: 99%

“…Brain sex steroids, especially E2, may cause brain sex differentiation at an early developmental age and lead to sexually dimorphic adult reproductive behaviors in mammals [8,9]. In addition, aromatase activity is regulated by estrogens and aromatizable androgens, and several studies in teleost fish indicate that cyp19a1b transcripts are up-regulated by E2 through estrogen receptor signaling [10][11][12][13], indicating the reproductive role and functional relationship of estrogen with brain aromatase. However, another study indicated that the cyp19a1b gene is also up-regulated by androgens, especially T, suggesting a potential androgenic regulation of cyp19a1b through the estrogen receptor [14].…”

Section: Introductionmentioning

confidence: 97%

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Developmental expression of genes involved in neural estrogen biosynthesis and signaling in the brain of the orange-spotted grouper Epinephelus coioides during gonadal sex differentiation

Nagarajan

Tsai

Chen

et al. 2011

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Introductionmentioning

confidence: 51%

Section: Rna Extraction Cdna Library Construction and Molecular Clonmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Developmental expression of genes involved in neural estrogen biosynthesis and signaling in the brain of the orange-spotted grouper Epinephelus coioides during gonadal sex differentiation

Nagarajan

Tsai

Chen

et al. 2011

The Journal of Steroid Biochemistry and Molecular Biology

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“…Furthermore, we propose that we have uncovered a temporal competency window for BPA effects on hypothalamic neurogenesis that is separate from estrogen signaling. This phenotype could be caused by changes in the expression of all three zebrafish ERs (ERα, ERβ1, and ERβ2), which increases dramatically between 24 and 48 hpf (53). Given that the peak of BPA susceptibility occurs at 24 hpf, and we show a role for ARs in BPA-mediated precocious neurogenesis, it will be interesting to see whether AR expression increases earlier than ER expression in the developing hypothalamus.…”

Section: Discussionmentioning

confidence: 85%

“…For example, proliferating cells in the developing cortex, hippocampus, olfactory bulb, and hypothalamus all express ERs (48) and ARs (25,49), and a clear role for sex steroids (e.g., estrogen, testosterone) in regulating neurogenesis in vivo (26,28) and in vitro (50, 51) is emerging, especially in the adult brain (27,29,52). In embryonic and adult zebrafish, ERs and AroB are coexpressed in hypothalamic radial glia and are thought to control differentiation and migrational changes that occur in response to estrogen exposure (29,53). These findings have led to the notion that AroB-expressing radial glia are plastic and initiate adult neurogenesis in response to estrogenic challenges as a way to maintain homeostatic physiologies (52).…”

Section: Discussionmentioning

confidence: 99%

Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish

Kinch

Ibhazehiebo

Jeong

et al. 2015

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

407

255

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Bisphenol A (BPA), a ubiquitous endocrine disruptor that is present in many household products, has been linked to obesity, cancer, and, most relevant here, childhood neurological disorders such as anxiety and hyperactivity. However, how BPA exposure translates into these neurodevelopmental disorders remains poorly understood. Here, we used zebrafish to link BPA mechanistically to disease etiology. Strikingly, treatment of embryonic zebrafish with very low-dose BPA (0.0068 μM, 1,000-fold lower than the accepted human daily exposure) and bisphenol S (BPS), a common analog used in BPA-free products, resulted in 180% and 240% increases, respectively, in neuronal birth (neurogenesis) within the hypothalamus, a highly conserved brain region involved in hyperactivity. Furthermore, restricted BPA/BPS exposure specifically during the neurogenic window caused later hyperactive behaviors in zebrafish larvae. Unexpectedly, we show that BPAmediated precocious neurogenesis and the concomitant behavioral phenotype were not dependent on predicted estrogen receptors but relied on androgen receptor-mediated up-regulation of aromatase. Although human epidemiological results are still emerging, an association between high maternal urinary BPA during gestation and hyperactivity and other behavioral disturbances in the child has been suggested. Our studies here provide mechanistic support that the neurogenic period indeed may be a window of vulnerability and uncovers previously unexplored avenues of research into how endocrine disruptors might perturb early brain development. Furthermore, our results show that BPA-free products are not necessarily safer and support the removal of all bisphenols from consumer merchandise.endocrine disruption | androgen receptor | aromatase | hyperactivity I n humans and rodent models, gestational exposure to bisphenol A (BPA) has been associated with increased risk of developing social (e.g., aggression), psychiatric (e.g., depression), and behavioral (e.g., hyperactivity) challenges later in life (1-7). BPA is a compound used in the production of diverse consumer products, ranging from baby bottles to thermal paper used for credit card receipts (8-10). Even though adults can experience adverse health following continued exposure to BPA, the fetal brain is especially vulnerable because of an immature xenobioticmetabolizing system and blood-brain barrier (11,12). Exactly how BPA exposure in utero translates into neurodevelopmental disorders later in life is only beginning to be explored (13-15).Despite a wide body of research illustrating adverse effects of BPA, controversy exists around the true effects of low-dose exposure, as is most often the case in humans. In accordance with standardized toxicological testing procedures, government agencies in the United States (the US Environmental Protection Agency, USEPA), Canada (Health Canada), and Europe (the European Food Safety Authority, EFSA) have established tolerable daily intake levels, ranging from 25-50 μg BPA·kg body weight [16][17][18]. Given th...

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Estrogenic regulation of claudin 5 and tight junction protein 1 gene expression in zebrafish: A role on blood–brain barrier?

Pellegrini,

Fernezelian,

Malleret

et al. 2023

J of Comparative Neurology

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The blood–brain barrier (BBB) is a physical interface between the blood and the brain parenchyma, playing key roles in brain homeostasis. In mammals, the BBB is established thanks to tight junctions between cerebral endothelial cells, involving claudin, occludin, and zonula occludens proteins. Estrogens have been documented to modulate BBB permeability. Interestingly, in the brain of zebrafish, the estrogen‐synthesizing activity is strong due to the high expression of Aromatase B protein, encoded by the cyp19a1b gene, in radial glial cells (neural stem cells). Given the roles of estrogens in BBB function, we investigated their impact on the expression of genes involved in BBB tight junctions. We treated zebrafish embryos and adult males with 17β‐estradiol and observed an increased cerebral expression of tight junction and claudin 5 genes in adult males only. In females, treatment with the nuclear estrogen receptor antagonist (ICI182,780) had no impact. Interestingly, telencephalic injuries performed in males decreased tight junction gene expression that was partially reversed with 17β‐estradiol. This was further confirmed by extravasation experiments of Evans blue showing that estrogenic treatment limits BBB leakage. We also highlighted the intimate links between endothelial cells and neural stem cells, suggesting that cholesterol and peripheral steroids could be taken up by endothelial cells and used as precursors for estrogen synthesis by neural stem cells. Together, our results show that zebrafish provides an alternative model to further investigate the role of steroids on the expression of genes involved in BBB integrity, both in constitutive and regenerative physiological conditions. The link we described between capillaries endothelial cells and steroidogenic neural cells encourages the use of this model in understanding the mechanisms by which peripheral steroids get into neural tissue and modulate neurogenic activity.

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Early regulation of brain aromatase (cyp19a1b) by estrogen receptors during zebrafish development

Cited by 83 publications

References 68 publications

Developmental expression of genes involved in neural estrogen biosynthesis and signaling in the brain of the orange-spotted grouper Epinephelus coioides during gonadal sex differentiation

Developmental expression of genes involved in neural estrogen biosynthesis and signaling in the brain of the orange-spotted grouper Epinephelus coioides during gonadal sex differentiation

Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish

Estrogenic regulation of claudin 5 and tight junction protein 1 gene expression in zebrafish: A role on blood–brain barrier?

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