Metallothionein gene expression under different time in testicular Sertoli and spermatogenic cells of rats treated with cadmium

Ren, Xu; Zhou, Yong; Zhang, Jian Peng; Feng, Wen; Jiao, Bing Hua

doi:10.1016/s0890-6238(02)00151-x

Cited by 38 publications

(23 citation statements)

References 46 publications

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“…The levels of MT-1 and MT-2 mRNA were relatively high in interstitial cells from untreated rats and increased after cadmium treatment peaking at levels approximating those measured in the liver at 6 h. While high basal levels of MT protein were detected in both interstitial cells and liver, the addition of cadmium increased protein levels in the liver, but slightly decreased levels in the interstitial cells. Similar results were found when MT-1 and MT-2 mRNAs were measured in rat testicular Sertoli cells and spermatogenic cells, although spermatogenic cell MT-2 mRNA levels decreased slightly in response to cadmium treatment [Ren et al 2003a]. As with the interstitial cells, no increase in MT protein was observed in Sertoli or spermatogenic cells as compared to liver cells in response to cadmium.…”

Section: Gene Polymorphisms: Potential Gene-environment Interactionssupporting

confidence: 84%

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Adverse Effects of Low Level Heavy Metal Exposure on Male Reproductive Function

Wirth

Mijal

2010

Systems Biology in Reproductive Medicine

245

164

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Lead, cadmium, mercury, and arsenic, often referred to as ''heavy metals'', are toxic for wildlife, experimental animals, and humans. While experimental animal and human occupational studies with high exposure levels generally support an adverse role for these metals in human reproductive outcomes, information on the effects of low, environmentally-realistic exposure levels of these metals on male reproductive outcomes is limited. We review the literature on effects of exposure to low levels of these metals on measures of male fertility (semen quality and reproductive hormone levels) and provide supporting evidence from experimental and occupational studies. Potentially modifying effects of genetic polymorphisms on these associations are discussed. A brief review of the literature on the effects of three trace metals, copper, manganese, and molybdenum, that are required for human health, yet may also cause adverse reproductive effects, follows. Overall, there were few studies examining the effects of exposure to low levels of these metals on male reproductive health. For all metals, there were several well-designed studies with sufficient populations appropriately adjusted for potential confounders and many of these reported harmful effects. However, many studies lacked sufficient numbers of participants to be able to detect differences in outcomes between exposed and non-exposed individuals, did not clearly identify the source and characteristics of the participants, and did not control for other exposures that could alter or contribute to the outcomes. The evidence for the effects of low exposure was strongest for cadmium, lead, and mercury and less certain for arsenic. The potential modifying effects of genetic polymorphisms has not been fully explored. Additional studies on the reproductive effects of these toxic ubiquitous metals on male reproduction are required to expand the knowledge base and to resolve inconsistencies.

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Section: Gene Polymorphisms: Potential Gene-environment Interactionssupporting

confidence: 84%

“…There appears to be a question, however, as to whether MT expressed constitutively in rodent testes or is it induced in response to cadmium treatment (see [Ren et al 2003a] for discussion). Two recent papers shed some light on the controversy.…”

Section: Gene Polymorphisms: Potential Gene-environment Interactionsmentioning

confidence: 99%

Adverse Effects of Low Level Heavy Metal Exposure on Male Reproductive Function

Wirth

Mijal

2010

Systems Biology in Reproductive Medicine

245

164

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“…However, there is a report indicating that MT-1/2 mRNA was induced by Cd in Sertoli cells, but not spermatogenic cells. The findings suggest that spermatogenic cells do not induce the metal-detoxicating MT protein in response to Cd (Ren et al, 2003). These results suggest that the male genital organs, particularly the testis, are extremely susceptible to Cd.…”

Section: Discussionmentioning

confidence: 84%

“…With respect to genotoxic agents, Cd is well known as a strong genotoxic metal and as a potent inducer of HO-1 (Yoshida et al, 1979) and MT-1/2 (Abe et al, 2000) in rats. Many researchers have examined HO-1 and MT-1/2 expression in testes in Cdadministered animals (Abe et al, 2000;Ozawa et al, 2002;Ren et al, 2003); however, it remains to be determined whether the induction of HO-1 and MT-1/2 in the testes by metals and chemicals is related to their genotoxic abilities.…”

Section: Introductionmentioning

confidence: 99%

Tissue-Dependent Induction of Heme Oxygenase-1 and Metallothionein-1/2 by Methyl Methanesulfonate

Ashino¹,

Ozawa

Numazawa³

et al. 2003

J. Toxicol. Sci.

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-Methyl methanesulfonate (MMS), a methylating agent, is known to be a genotoxicant in testis. The purpose of this study was to investigate roles of oxidative stress-responsive proteins, heme oxygenase-1 (HO-1) and metallothionein-1/2 (MT-1/2), in genotoxicity of MMS. Cadmium, a potent genotoxicity inducer, induced HO-1 and MT-1/2 in rat livers and kidneys. Then we comparatively investigated MMS-induced HO-1 and MT-1/2 in rat livers, kidneys and testes. We found that a single administration of MMS (40 mg/kg) resulted in the induction of MT-1/2 mRNA in the liver, but not HO-1 mRNA, reaching maximum level at 6 hr and returning to the control levels by 24 hr. Interestingly, MMS induced both HO-1 and MT-1/2 mRNAs in the kidney. In contrast, MMS induced HO-1 mRNA, but not MT-1/2 mRNA in the testis. Since HO-1 and MT-1/2 have been recognized to respond to various oxidative stimuli, we further examined the inducing effect of MMS on these two proteins. MMS at dosages of 20 to 40 mg/kg for 2 consecutive weeks induced HO-1 mRNA (123 to 187% of the control) and protein (274 to 404% of the control) in rat testes. However, MT-1/2 mRNA was not induced by MMS administration, although a high level of expression was observed in comparison with the liver and kidney. These findings suggest that MMS induces HO-1 and/or MT-1/2 mRNA and its protein tissue-dependently, and the heme catabolites by HO-1 in the testis may contribute in some manner to its genotoxicity.

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“…Expressions of MT3 and MT4 are restricted to brain and reproductive organs, as well as to stratified squamous epithelia of the skin and tongue, respectively (21,22). While MT3 and MT4 are constitutively expressed, MT1 and MT2 are coordinately regulated by a variety of developmental and environmental signals, such as metals, oxidative stress, cytokines and glucocorticoid hormones (23,24). The major function of MT is to preserve the homeostasis of biologically essential metals such as zinc and copper, and to detoxify poisonous metals, such as cadmium and mercury (17,18,25).…”

Section: Discussionmentioning

confidence: 99%

Detection of metallothionein 1G as a methylated tumor suppressor gene in human hepatocellular carcinoma using a novel method of double combination array analysis

Kanda

Nomoto²,

Okamura³

et al. 2009

Int J Oncol

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Abstract. Gene expression profiling or karyotyping analysis has made it possible to identify novel genes with altered expressions or copy numbers that have not been previously reported in liver cancer. On the same HCC sample, we performed double array analysis, both expression profiling and karyotyping analysis using a single nucleotide polymorphism (SNP) array in an attempt to find a novel tumor suppressor gene for its prognostic marker. We conducted expression array and SNP chip array using tumor and corresponding non-tumor tissues from the resected liver specimen of a 68-year-old woman who had chronic hepatitis type C. Additionally, we performed quantitative real-time reverse transcription polymerase chain reaction (PCR) and methylationspecific PCR (MSP) for gene detection using specimens from 48 patients with HCC, and investigated their correlation with the prognosis. Metallothionein (MT) 1G gene located on 16q13 showed a decreased expression in tumor tissue. The copy number by SNP chip array revealed no loss of heterozygosity since no deletions were detected in 16q13, and HCC tissue showed AB call in both SNPs next to MT1G. In quantitative real-time PCR using 48 HCC clinical samples, mRNA expression of MT1G decreased significantly compared with that in corresponding non-cancerous liver tissues (p<0.0323). Twenty-nine (60.4%) of 48 HCCs gave a positive result in MSP, indicating a poorer prognosis than the negative group, although the difference was not significant (p<0.0978). Our results indicated that MT1G acts as a tumor suppressor gene in HCC. Moreover, findings suggested that the mechanisms of MT1G silencing are related to promoter hypermethylation.

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Metallothionein gene expression under different time in testicular Sertoli and spermatogenic cells of rats treated with cadmium

Cited by 38 publications

References 46 publications

Adverse Effects of Low Level Heavy Metal Exposure on Male Reproductive Function

Adverse Effects of Low Level Heavy Metal Exposure on Male Reproductive Function

Tissue-Dependent Induction of Heme Oxygenase-1 and Metallothionein-1/2 by Methyl Methanesulfonate

Detection of metallothionein 1G as a methylated tumor suppressor gene in human hepatocellular carcinoma using a novel method of double combination array analysis

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