2,3,7,8-tetrachlorodibenzo-p-dioxin reduces the number, size, and organelle content of Leydig cells in adult rat testes

Johnson, Larry; Wilker, Clynn E.; Safe, Stephen; Scott, Beth E.; Dean, Dana D.; White, Phillip H.

doi:10.1016/0300-483x(94)90132-5

Cited by 47 publications

(23 citation statements)

References 25 publications

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“…In vivo TCDD has been shown to decrease hormone production in mouse antral follicles (Karman et al, 2012) and the number and size of Leydig cells in rats, which is likely to affect testosterone production (Johnson et al, 1994). TCDD might affect steroidogenesis by interfering with the hypothalamic-pituitary-adrenal (HPA) axis, but these effects cannot be investigated by the current H295R cell model.…”

Section: Hormonementioning

confidence: 97%

Steroid hormone related effects of marine persistent organic pollutants in human H295R adrenocortical carcinoma cells

Dungen

Rijk

Kampman

et al. 2015

Toxicology in Vitro

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Section: Hormonementioning

confidence: 97%

Steroid hormone related effects of marine persistent organic pollutants in human H295R adrenocortical carcinoma cells

Dungen

Rijk

Kampman

et al. 2015

Toxicology in Vitro

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“…Reductions in gonadal size and function are also associated with PCB exposure in rodent studies, even at levels approaching those found as background in human populations (Johnson et al, 1994;Smolowitz and Leavitt, 1996). In the present study, we observed similar reductions in gonadal cross-sectional area in Corbicula exposed to Aroclor 1260.…”

Section: Histopathologymentioning

confidence: 99%

Polychlorinated Biphenyl Exposure Causes Gonadal Atrophy and Oxidative Stress in Corbicula fluminea Clams

2007

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Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that have been linked to oxidative and other toxic effects in both humans and wildlife. Due to recent environmental health concerns at a PCB contaminated Superfund site near Raleigh, NC, we used a common clam species (Corbicula fluminea) as surrogates to isolate the effects of PCBs on threatened bivalves native to the region. Under controlled laboratory conditions, clams were exposed to 0, 1, 10, or 100 ppb Aroclor 1260 in the ambient water for 21 days. Measured biomarkers spanned a range of effective levels of biological organization including low molecular weight antioxidants, lipid-soluble antioxidants, and whole tissue radical absorption capacity. These data were augmented by use of histological evaluation of whole samples. Aroclor 1260 significantly increased reduced glutathione (GSH) and total protein concentrations at all treatments levels. Significant decreases were measured in all treatments in γ -tocopherol and total oxidant scavenging capacity (TOSC) and α-tocopherol values in the 100 ppb exposure. Histologically, Aroclor 1260 caused significant gonadal atrophy, effacement of gonad architecture with accumulations of Brown cells, and inflammation and necrosis in digestive glands and foot processes. Our results indicate that oxidative mechanisms play a significant role in the decreased health of these clams due to exposure to Aroclor 1260. The changes in the gonads of exposed clams suggest that a serious threat to bivalve reproduction exists due to PCB exposure.

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“…AHR ligands include polycyclic aromatic hydrocarbons and dioxins, which are environmental pollutants known to lower Leydig cell number, impair cholesterol mobilization, inhibit steroidogenic enzyme activity, and perturb androgen production and action. This leads to defects in the development of the male reproductive tract and external genitalia (reviewed in [40], see also [41][42][43]) and fertility disorders in humans [44]. One of the downstream targets of AHR is Cyp1b1 [39], which encodes an enzyme involved in drug metabolism.…”

Section: /Map2k2mentioning

confidence: 99%

Novel Targets for the Transcription Factors MEF2 in MA-10 Leydig Cells1

Di-Luoffo

Daems

Bergeron

et al. 2015

Biology of Reproduction

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Testosterone production by Leydig cells is a tightly regulated process requiring synchronized expression of several steroidogenic genes by numerous transcription factors. Myocyte enhancer factor 2 (MEF2) are transcription factors recently identified in somatic cells of the male gonad. In other tissues, MEF2 factors are essential regulators of organogenesis and cell differentiation. So far in the testis, MEF2 factors were found to regulate Leydig cell steroidogenesis by controlling Nr4a1 and Star gene expression. To expand our understanding of the role of MEF2 in Leydig cells, we performed microarray analyses of MEF2-depleted MA-10 Leydig cells, and the results were analyzed using Partek and Ingenuity Pathway Analysis software. Several genes were differentially expressed in MEF2-depleted Leydig cells, and 16 were validated by quantitative RT-PCR. A large number of these genes are known to be involved in fertility, gonad morphology, and steroidogenesis. These include Ahr, Bmal1, Cyp1b1, Hsd3b1, Hsd17b7, Map2k1, Nr0b2, Pde8a, Por, Smad4, Star, and Tsc22d3, which were all downregulated in the absence of MEF2. In silico analyses revealed the presence of MEF2-binding sites within the first 2 kb upstream of the transcription start site of the Por, Bmal1, and Nr0b2 promoters, suggesting direct regulation by MEF2. Using transient transfections in MA-10 Leydig cells, small interfering RNA knockdown, and a MEF2-Engrailed dominant negative, we found that MEF2 activates the Por, Bmal1, and Nr0b2 promoters and that this requires an intact MEF2 element. Our results identify novel target genes for MEF2 and define MEF2 as an important regulator of Leydig cell function and male reproduction. fertility, gonad morphology, Leydig cells, microarray, myocyte enhancer factor 2, steroidogenesis

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2,3,7,8-tetrachlorodibenzo-p-dioxin reduces the number, size, and organelle content of Leydig cells in adult rat testes

Cited by 47 publications

References 25 publications

Steroid hormone related effects of marine persistent organic pollutants in human H295R adrenocortical carcinoma cells

Steroid hormone related effects of marine persistent organic pollutants in human H295R adrenocortical carcinoma cells

Polychlorinated Biphenyl Exposure Causes Gonadal Atrophy and Oxidative Stress in Corbicula fluminea Clams

Novel Targets for the Transcription Factors MEF2 in MA-10 Leydig Cells1

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