Internal dose-effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in gonadotropin-primed weanling rat model

Shirota, Mariko; Kaneko, Toyozo; Okuyama, Mitsunobu; Sakurada, Yosuke; Shirota, Kinji; Matsuki, Yasuhiko

doi:10.1007/s00204-006-0146-5

Cited by 5 publications

(2 citation statements)

References 31 publications

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“…The sequences of those for growth differentiation factor-9 (GDF-9), bone morphogenetic protein-15 (BMP-15), c-kit and kit ligand are shown in Table 1. Sequences of the others, including the inhibin α-subunit, inhibin/activin βA-and βB-subunits, FSH receptor, luteinizing hormone (LH) receptor and aromatase, have been described previously [13]. To determine the amount of glyceraldehyde-3-phosphatase dehydrogenase (GAPDH) mRNA, a commercially available probe and primers, the TaqMan Rodent GAPDH Control Reagents (Applied Biosystems), were used in the present study.…”

Section: Quantitative Analysis Of Gene Expression In the Ovarymentioning

confidence: 99%

Effects of Vertically Transferred 3,3',4,4',5-Pentachlorobiphenyl on Gene Expression in the Ovaries of Immature Sprague-Dawley Rats

Sakurada

Shirota

Mukai

et al. 2007

Journal of Reproduction and Development

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Abstract.We have previously shown that 3,3',4,4',5-pentachlorobiphenyl (PCB-126) vertically transferred from dams potentially exerts a direct effect on the ovaries of offspring and adversely affects female puberty. To investigate its toxicological targets in ovarian tissues, mRNAs encoding representative peptides that regulate follicular development in granulosa cells, theca cells, and oocytes were quantified using ovaries collected on postnatal days (PND) 5, 15, and 24 from the offspring of dams administered oral doses of 0, 1 or 3 µg/kg PCB-126 starting 2 weeks prior to mating and continuing until 20 days after delivery. Quantification using the real-time RT-PCR method revealed that PCB-126 lowered the amounts of mRNAs that encoded the inhibin α-and inhibin/ activin βA-subunits from PND 15 onwards; the amounts of mRNAs for inhibin/activin βB-subunit, follicle-stimulating hormone (FSH) receptor, and aromatase on PND 15; and the amounts of luteinizing hormone receptor mRNA on PND 24 compared with those of the age-matched controls. In contrast, no differences were noted for mRNAs encoding c-kit, growth differentiation factor-9, bone morphogenetic protein-15, or kit ligand for any of the age groups examined. The serum FSH level on PND 24 was higher than that in the control. Since the earliest effects on the mRNAs in the rat ovaries were observed in those expressed in the granulosa cells of the growing follicles after the antral follicles had developed, molecules in granulosa cells but not in oocytes during the early stages of the antral follicles might be the primary targets of vertically transferred PCB-126.

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Section: Quantitative Analysis Of Gene Expression In the Ovarymentioning

confidence: 99%

Effects of Vertically Transferred 3,3',4,4',5-Pentachlorobiphenyl on Gene Expression in the Ovaries of Immature Sprague-Dawley Rats

Sakurada

Shirota

Mukai

et al. 2007

Journal of Reproduction and Development

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“…Treatment with AhR agonists such as 2,3,7,8-tetrachlorodibenzo-pdioxin [16] and 3,3',4,4',5-pentachlorobiphenyl (PCB 126) [17] increases cytochrome P450 (CYP) 1A1 mRNA, a phase I enzyme, in rat ovaries, indicating that AhR signaling cascades are activated. Ligand-activated AhR regulates the ovarian atresia in primordial and primary follicles via activation of the Bax signaling pathway [9,10], and ovotoxicity induced by PAH is prevented by the concomitant treatment with AhR antagonists, thus indicating that AhR is the key mediator of ovotoxicity [11].…”

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Comparison of Aryl Hydrocarbon Receptor Gene Expression in Laser Dissected Granulosa Cell Layers of Immature Rat Ovaries

Sakurada

Sawai

Inoue

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. In order to understand ovarian toxicity of aryl hydrocarbon receptor (AhR) agonists, in situ gene expression of the AhR was examined during follicle development in immature rats. In situ hybridization on frozen sections of ovaries from 24-day-old SpragueDawley rats showed that the AhR mRNA was localized in the granulosa cells and occasionally in the theca cells of the follicles irrespective of the developmental stage. In situ gene quantification on granulosa cell layers collected by laser microdissection further revealed that the granulosa cells expressed less AhR mRNA according to development of belonging follicles, but more -subunit of inhibin A mRNA, a quality control gene. These results may help to elucidate vulnerable developmental stages of follicles to toxicities of the AhR agonists.KEY WORDS: aryl hydrocarbon receptor (AhR), -subunit of inhibin A, follicular development, laser microdissection, ovary.J. Vet. Med. Sci. 73(7): 923-926, 2011 Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates toxicity of AhR agonists, such as the polycyclic aromatic hydrocarbons (PAHs) [2,6,12], and is expressed in mammalian ovaries [2]. Treatment with AhR agonists such as 2,3,7,8-tetrachlorodibenzo-pdioxin [16] and 3,3',4,4', [17] increases cytochrome P450 (CYP) 1A1 mRNA, a phase I enzyme, in rat ovaries, indicating that AhR signaling cascades are activated. Ligand-activated AhR regulates the ovarian atresia in primordial and primary follicles via activation of the Bax signaling pathway [9,10], and ovotoxicity induced by PAH is prevented by the concomitant treatment with AhR antagonists, thus indicating that AhR is the key mediator of ovotoxicity [11]. Although AhR has been confirmed in oocytes, granulosa and theca cells of growing follicles in the rat by its mRNA and protein expression levels [4,13], little has been studied precise expression level of the AhR in the follicles at each developmental stage. Therefore, the present study was designed to examine in situ expression of the AhR mRNA by in situ hybridization (ISH) and gene quantification of laser-dissected granulosa cell layers from healthy follicles at different developmental stages. The mRNA encoding the -subunit of inhibin A was also quantified to confirm the quality of the dissected specimens, since striking and dynamic changes of the -subunit of inhibin A mRNA have been detected in rats during developmental maturation of the follicles [18], and increased inhibin A secretion occurs with the advancing estrous cycle up to the LH surge [8].In this study, three females born in our animal facility from pregnant Sprague-Dawley rats (Charles River Japan, Yokohama, Japan) were used after weaning on postnatal day (PND) 21 in accordance with the guidelines approved by the Animal Research Committee of Azabu University. On PND 24, the rats were sacrificed by decapitation, and their ovaries were collected, frozen in liquid nitrogen and stored at -80C until analyses.For the ISH and the in situ gene quantification, frozen ...

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Cigarette smoke causes follicle loss in mice ovaries at concentrations representative of human exposure

2009

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Internal dose-effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in gonadotropin-primed weanling rat model

Cited by 5 publications

References 31 publications

Effects of Vertically Transferred 3,3',4,4',5-Pentachlorobiphenyl on Gene Expression in the Ovaries of Immature Sprague-Dawley Rats

Effects of Vertically Transferred 3,3',4,4',5-Pentachlorobiphenyl on Gene Expression in the Ovaries of Immature Sprague-Dawley Rats

Comparison of Aryl Hydrocarbon Receptor Gene Expression in Laser Dissected Granulosa Cell Layers of Immature Rat Ovaries

Cigarette smoke causes follicle loss in mice ovaries at concentrations representative of human exposure

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