Effect of maternal exposure to dioxin on the pituitary and hypothalamic expression of genes in PND70 male pups
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE48100 | GEO | 2013/08/21
SECONDARY ACCESSION(S): PRJNA208933
REPOSITORIES: GEO
Similar Datasets
Project description:Our previous studies have revealed that treatment of pregnant rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1 M-NM-<g/kg) at gestational day (GD) 15 reduces the pituitary synthesis of luteinizing hormone (LH) during late fetal and early postnatal period, leading to imprinting of defects in sexual behaviors at adulthood. However, it remains obscure how the attenuation of pituitary LH links to sexual immaturity. To address this issue, we firstly performed a DNA microarray analysis to identify the gene(s) responsible for dioxin-induced sexual immaturity, using the pituitary and hypothalamus of male pups, at the age of postnatal day (PND)70, born from TCDD-treated dams. Among the reduced genes, we focused on gonadotropin-releasing hormone (GnRH) in the hypothalamus, because of its role in sexual behaviors suggested so far. The present study strongly suggests that maternal exposure to TCDD fixes the status of the lowered expression of GnRH in the offspring by reducing steroidogenesis at perinatal stage, and this is the mechanism for the imprinting of defects in sexual behaviors at adulthood. Total RNA was isolated from the pituitary and hypothalamus of PND70 male pups born from the dams treated with TCDD (1 M-NM-<g/kg) or vehicle at GD15, using an RNeasy Mini Kit (QIAGEN). To identify the gene(s) the altered expression of which is fixed and linked to defects in sexual behaviors, the profile of gene expression was analyzed using the Illumina RatRef-12 Expression BeadChip. This series includes two dataset; hypothalamic and pituitary samples (each case; N=3x2). The normalization applied each dataset.
2013-08-21 | E-GEOD-48100 | biostudies-arrayexpress
Project description:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes the many forms of reproductive toxicity, such as defects in sexual behaviors, in pups of which mother is exposed to this substance at lower doses. However, the mechanism underlying these defects remains to be clarified in spite of many researches conducted so far. Our previous studies have revealed that maternal treatment with TCDD attenuates the production of pituitary gonadotropins [luteinizing hormone (LH) and follicle-stimulating hormone] in the late fetuses, leading to the impairment of sexual behavior in adulthood. To identify the target genes for a fetal reduction in gonadotropin β-subunit, we performed DNA microarray analysis using the fetal pituitary and its regulatory organ, the hypothalamus. The result showed that TCDD induced histone deacetylases (HDACs), and altered the expression of genes including gonadotropin-releasing hormone and activin signaling in the fetal pituitary. Moreover, our data indicated that the increased deacetylation of histone due to HDAC induction plays a critical role for a dioxin-induced attenuation of LHβ in the fetal pituitary. This study suggests a novel molecular mechanism explaining dioxin-produced reproductive toxicity. Pregnant Wistar rats were orally treated with TCDD (1 µg/kg in corn oil) at gestational day (GD)15. Then, the total RNA was extracted from the fetal pituitary and hypothalamus at GD20. To identify the target genes the alteration of which contributes to a reduction in fetal gonadotropin β-subunit, the profile of gene expression was analyzed using the Illumina RatRef-12 Expression BeadChip.
2011-09-30 | E-GEOD-32459 | biostudies-arrayexpress
Project description:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes the many forms of reproductive toxicity, such as defects in sexual behaviors, in pups of which mother is exposed to this substance at lower doses. However, the mechanism underlying these defects remains to be clarified in spite of many researches conducted so far. Our previous studies have revealed that maternal treatment with TCDD attenuates the production of pituitary gonadotropins [luteinizing hormone (LH) and follicle-stimulating hormone] in the late fetuses, leading to the impairment of sexual behavior in adulthood. To identify the target genes for a fetal reduction in gonadotropin β-subunit, we performed DNA microarray analysis using the fetal pituitary and its regulatory organ, the hypothalamus. The result showed that TCDD induced histone deacetylases (HDACs), and altered the expression of genes including gonadotropin-releasing hormone and activin signaling in the fetal pituitary. Moreover, our data indicated that the increased deacetylation of histone due to HDAC induction plays a critical role for a dioxin-induced attenuation of LHβ in the fetal pituitary. This study suggests a novel molecular mechanism explaining dioxin-produced reproductive toxicity.
2011-10-01 | GSE32459 | GEO
Project description:Gonadotropin-releasing hormone (GnRH) governs reproduction in vertebrates by regulating pituitary gonadotropins. Zebrafish, however, is an exception as gnrh3–/– fish, which lack the hypophysiotropic GnRH3, are fertile, suggesting that zebrafish utilizes a Gnrh-independent mechanism to regulate reproduction. To elucidate the role of Gnrh3 and the Gnrh-independent mechanisms that regulate the pituitary gonadotropes, we profiled the gene expression in individual pituitary cells of wild-type and gnrh–/– adult female zebrafish and identified transcriptionally defined cell types. The classical Lh and Fsh gonadotropes expressed both gonadotropin beta subunits with a ratio of 13:1 (lhb:fshb) and 40:1 (fshb:lhb), respectively. We discovered that Lh gonadotropes predominantly express genes encoding receptors for Gnrh (gnrhr2), thyroid hormone, estrogen, dopamine, and steroidogenic factor 1 (SF1). No Gnrh receptor expression was enriched in Fsh gonadotropes, instead, the expression of cholecystokinin receptor (cckrb) and galanin receptor (gal1rb) were enriched in these cells. The hereditary loss of Gnrh3 gene resulted in downregulation of fshb in Lh gonadotropes. Likewise, targeted chemogenetic ablation of Gnrh3 neurons led to a decrease in the number of fshb+/lhb+ cells. Our studies suggest that Gnrh3 directly acts on Lh gonadotropes through Gnrhr2, but the outcome of this interaction is still unknown. Gnrh3 also regulates fshb expression, probably via a non-Gnrh receptor route. Altogether, while Lh secretion and synthesis are likely regulated by multiple factors in a Gnrh-independent manner, Gnrh3 seems to play a role in the cellular organization of the pituitary in zebrafish.
2024-11-20 | GSE272806 | GEO
Project description:This a model from the article:
A mathematical model of luteinizing hormone release from ovine pituitary cells
in perifusion.
Heinze K, Keener RW, Midgley AR Jr. Am J Physiol
1998 Dec;275(6 Pt 1):E1061-71 9843750
,
Abstract:
We model the effect of gonadotropin-releasing hormone (GnRH) on the production
of luteinizing hormone (LH) by the ovine pituitary. GnRH, released by the
hypothalamus, stimulates the secretion of LH from the pituitary. If stimulus
pulses are regular, LH response will follow a similar pattern. However, during
application of GnRH at high frequencies or concentrations or with continuous
application, the pituitary delivers a decreased release of LH (termed
desensitization). The proposed mathematical model consists of a system of
nonlinear differential equations and incorporates two possible mechanisms to
account for this observed behavior: desensitized receptor and limited, available
LH. Desensitization was provoked experimentally in vitro by using ovine
pituitary cells in a perifusion system. The model was fit to resulting
experimental data by using maximum-likelihood estimation. Consideration of
smaller models revealed that the desensitized receptor is significant. Limited,
available LH was significant in three of four chambers. Throughout, the proposed
model was in excellent agreement with experimental data.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Heinze K, Keener RW, Midgley AR Jr. (1998) - version02
The original CellML model was created by:
Lloyd, Catherine, May
c.lloyd@aukland.ac.nz
The University of Auckland
The Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL0848507209 | BioModels
Project description:We determined global gene changes in immature ovaries and testes in response to an in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. Microarray analysis was performed using testes and ovaries of the dioxin-exposed dams’ offspring. One hundred and thirteen genes were differentially expressed in ovaries and 56 genes in testes of 14 and 5 days-old, respectively. Real-time PCR was used to validate and extend data using RNA extracted from 5 to 145-day old rat testes and 3 to 25-day old rat ovaries. A single gene of the classic dioxin battery, i.e., the repressor of the aryl hydrocarbon receptor (Ahrr) was found altered in testes. In contrast, several of them including Cyp1a1, Cyp1b1, Nqo1, and Ahrr were found up-regulated in ovary, pituitary (a different endocrine organ) and liver. In addition to Ahrr, we identified 6 genes targeted by dioxin in both gonads, including the chemokines Cxcl4, Ccl5. Ccl5 gene expression levels were also regulated in pituitary and liver, so as pituitary Cxcl4. Four genes targeted by TCDD in testis and meeting stringent criteria were further surveyed. It included 2 genes with no previous reported function in testis, Art2b, Gzmf, Hpgds and Fgf13. Fgf13 was down-regulated in testis, and pituitary but not in ovary or liver. Interestingly, Art2b and Gzmf were up-regulated in testis, liver and pituitary but not ovary. Finally, Hpgds was unique in that expressed in various tissues it was regulated by TCDD in the gonads but not in the other tissues studied. Transcriptomic analysis on testes at 5 days and in ovaries at 14 days. In both cases, 3 rats treated in utero by TCDD were compared to 3 rats treated with sesame-oil vehicle
2011-10-11 | E-GEOD-32890 | biostudies-arrayexpress
Project description:We report the RNAseq-based transcriptome profiles of rat gestation day 20 dam liver, fetal male and female liver, fetal male pituitary, and fetal testis following in utero exposure to either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 2,3,7,8-tetrachlorodibenzofuran (TCDF). Two exposure models were examined: 1) pregnant rats exposed to either a dose response series of TCDD or TCDF from gestation day 6 - 20 or 2) pregnant rats exposed to a single dose of TCDD or TCDF on gestation day 15. These data support a mode-of-action for dioxin-induced rat male reproductive toxicity involving key events in both the fetal pituitary (reduced gonadotropin production) and fetal testis (reduced Leydig cell cholesterologenesis and steroidogenesis) which are hypothesized to decrease perinatal Sertoli cell proliferation and culminate in reduced spermatogenesis. The lack of a TCDF effect on proposed key events may be due to a higher rate of metabolic clearance relative to TCDD.
2019-12-15 | GSE128824 | GEO
Project description:Introduction: reproduction in fish, as in all vertebrates, is regulated by GnRH control on gonadotropic hormones (GTH) activity. However, the neuroendocrine factors that promote GnRH and GTH activity are unknown. In Nile tilapia (Oreochromis niloticus), sexual activity and the ability to reproduce depend on social rank; only dominant males and females reproduce. Here, this characteristic of dominant fish allows us to compare brain and pituitary gene expression in animals that do and do not reproduce, aiming to reveal mechanisms that regulate reproduction. Methods: an extensive transcriptome analysis was performed, combining two sets of transcriptomes: a novel whole-brain and pituitary transcriptome of established dominant males identified by behavioral assays, together with a cell-specific transcriptome of LH and FSH cells. Results: in most dominant fish, as determined behaviorally, the gonadosomatic index (GSI) was higher than in subordinate fish, and the leading upregulated pituitary genes were those coding for GTHs. In the brain, various neuropeptide genes, including oxytocin, cholecystokinin, and MCH, were upregulated; these may be related to reproductive status through effects on behavior and feeding. In a network analysis combining the two transcriptome sets, brain aromatase (cyp19a1b), which is specifically expressed in LH cells, is the most central gene with the highest number of connections. Conclusions: the close correlation between behavioral dominance and reproductive capacity in tilapia allows us to unravel novel genes that may partake in the regulation of the HPG axis, highlighting aromatase as an important factor in integrating the brain and pituitary factors that maintain a sexually active organism.
2022-04-30 | GSE169272 | GEO
Project description:We determined global gene changes in immature ovaries and testes in response to an in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. Microarray analysis was performed using testes and ovaries of the dioxin-exposed dams’ offspring. One hundred and thirteen genes were differentially expressed in ovaries and 56 genes in testes of 14 and 5 days-old, respectively. Real-time PCR was used to validate and extend data using RNA extracted from 5 to 145-day old rat testes and 3 to 25-day old rat ovaries. A single gene of the classic dioxin battery, i.e., the repressor of the aryl hydrocarbon receptor (Ahrr) was found altered in testes. In contrast, several of them including Cyp1a1, Cyp1b1, Nqo1, and Ahrr were found up-regulated in ovary, pituitary (a different endocrine organ) and liver. In addition to Ahrr, we identified 6 genes targeted by dioxin in both gonads, including the chemokines Cxcl4, Ccl5. Ccl5 gene expression levels were also regulated in pituitary and liver, so as pituitary Cxcl4. Four genes targeted by TCDD in testis and meeting stringent criteria were further surveyed. It included 2 genes with no previous reported function in testis, Art2b, Gzmf, Hpgds and Fgf13. Fgf13 was down-regulated in testis, and pituitary but not in ovary or liver. Interestingly, Art2b and Gzmf were up-regulated in testis, liver and pituitary but not ovary. Finally, Hpgds was unique in that expressed in various tissues it was regulated by TCDD in the gonads but not in the other tissues studied.
2011-10-12 | GSE32890 | GEO
Project description:In many mammals, halogenated aromatic hydrocarbon (HAH) exposure causes wasting syndrome, defined as lethal weight loss as a result of severe and persistent hypophagia. The most potent HAH in causing wasting is 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), which exerts its toxic effects through the aryl hydrocarbon receptor (AHR) – a transcription factor. Because TCDD toxicity is thought to predominantly arise from dysregulation of AHR-transcribed genes, we hypothesized that wasting syndrome is due to TCDD-induced dysregulation of genes involved in regulation of food-intake. We therefore focused on the hypothalamus, as it is the regulatory center of food-intake and energy balance in the central nervous system. We profiled mRNA abundance in hypothalamic tissue from two rat strains with widely differing sensitivities to wasting syndrome: TCDD-sensitive Long-Evans rats and TCDD-resistant Han/Wistar rats, 23 hours after exposure to TCDD (100 μg/kg) or corn oil vehicle. We found that TCDD exposure caused minimal transcriptional dysregulation effects in the hypothalamus, with only 6 genes changed in Long-Evans rats and 15 genes in Han/Wistar rats. Two of the most dysregulated genes were Cyp1a1 and Nqo1, which are induced by TCDD across a wide range of tissues and are considered sensitive markers of TCDD exposure. The minimal response of the hypothalamic transcriptome to a lethal dose of TCDD at an early time-point suggests that the hypothalamus is not the predominant site of initial events leading to hypophagia and associated wasting. TCDD may affect feeding behaviour via events upstream or downstream of the hypothalamus, and further work is required to evaluate this at the level of individual hypothalamic nuclei and subregions. Two strains, each with drug-treated vs vehicle-control
2014-12-23 | E-GEOD-61039 | biostudies-arrayexpress