Bisphenol A (BPA) is commonly used in the production of pharmaceutical, industrial, and housing epoxy, as well as polycarbonate plastics. Owing to its extensive use, BPA can contaminate the environment either directly or through derivatives of these products. BPA has been classified as an endocrine ...
Bisphenol A (BPA) is commonly used in the production of pharmaceutical, industrial, and housing epoxy, as well as polycarbonate plastics. Owing to its extensive use, BPA can contaminate the environment either directly or through derivatives of these products. BPA has been classified as an endocrine disruptor chemicals (EDCs), and the primary toxicity of these EDCs in males involves the induction of reproductive system abnormality. First, in order to evaluate the direct effects on the Y chromosome associated with reproduction, we evaluated Y chromosome abnormalities using a Y chromosome microdeletion detection kit. However, we detected no Yq abnormality as the result of BPA exposure. Secondly, we performed high-density oligonucleotide array-based comparative genome hybridization (CGH) to assess genomic alteration as a component of our toxicity assessment. The results of our data analysis revealed some changes in copy number. Seven observed features were gains or losses in chromosomal DNA (P-value0.2). Interestingly, 21 probes of chr7:7312289-10272836 (qA1-qA2 in cytoband) were a commonly observed amplification (P-value 3.69e-10). Another region, chr14:4551029-10397399, was also commonly amplified (P-value 2.93e-12, average of log2 ratios in segment>0.3786). These regions include many genes associated with pheromone response, transcription, and signal transduction using ArrayToKegg software. These results help us to understand the molecular mechanisms underlying the reproductive effects induced by BPA.
Bisphenol A (BPA) is commonly used in the production of pharmaceutical, industrial, and housing epoxy, as well as polycarbonate plastics. Owing to its extensive use, BPA can contaminate the environment either directly or through derivatives of these products. BPA has been classified as an endocrine disruptor chemicals (EDCs), and the primary toxicity of these EDCs in males involves the induction of reproductive system abnormality. First, in order to evaluate the direct effects on the Y chromosome associated with reproduction, we evaluated Y chromosome abnormalities using a Y chromosome microdeletion detection kit. However, we detected no Yq abnormality as the result of BPA exposure. Secondly, we performed high-density oligonucleotide array-based comparative genome hybridization (CGH) to assess genomic alteration as a component of our toxicity assessment. The results of our data analysis revealed some changes in copy number. Seven observed features were gains or losses in chromosomal DNA (P-value0.2). Interestingly, 21 probes of chr7:7312289-10272836 (qA1-qA2 in cytoband) were a commonly observed amplification (P-value 3.69e-10). Another region, chr14:4551029-10397399, was also commonly amplified (P-value 2.93e-12, average of log2 ratios in segment>0.3786). These regions include many genes associated with pheromone response, transcription, and signal transduction using ArrayToKegg software. These results help us to understand the molecular mechanisms underlying the reproductive effects induced by BPA.
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문제 정의
This study may help us to understand toxicogenomics approaches utilizing array-based CGH.
가설 설정
Recent genetic studies of male infertility have demonstrated that the long arm of the Yq harbors at least 15 families, some of which have been shown to be necessary for spermatogene- sis6, 7. We hypothesize that male reproductive abnormality may arise as a problem of Y chromosome-mic- rodeletion as the consequence of exposure to BPA. We assessed genomic abnormalities of the Y chromosome using a multiplex-PCR-based Y chromosome microdeletion detection kit in in vitro systems.
제안 방법
Probe design and selection have been carefully optimized and validated for maximal sensitivity and specificity. In this study, therefore, we examined high-resolution array-based CGH for the evaluation of genetic alterations caused by BPA exposure.
numbers. In this study, we assessed variations in the DNA copy number by BPA-treatment using array-based CGH. We determined that some DNA copy numbers changed after BPA treatment-four regions increased and three regions decreased.
The control mice were given corresponding quantities of the vehicle. The mice were sacrificed after 30 days and were carefully dissected in order to count the sperm and collect tissue samples. Five or six animals were used in each experiment.
To assess the genomic alterations in the mice testes as a result of BPA exposure, we utilized oligonucleotide array-based CGH, with an Agilent mouse genome CGH 105K array. The Agilent CGH array enables the detection of genomic alterations with a resolution of 10 kb in the BPA-treated mice.
대상 데이터
The mice were sacrificed after 30 days and were carefully dissected in order to count the sperm and collect tissue samples. Five or six animals were used in each experiment. Relative organ weight was calculated as the ratio of the right organ weight to body weight.
이론/모형
14 software (Agilent Technologies, CA). Following data extraction and normalization, we selected the region of copy mjmbeT variation using the ADM2 finding method. A total of seven features were detected in the regions of DNA copy number variation in the BPA- treated mice (Table 2, Figure 2).
성능/효과
In conclusion, although our study did not clearly demonstrate the mechanisms relevant to toxicity in the male reproductive system, we know that BPA causes variations in DNA copy numbers in specific regions, most notably an abundance of pheromone receptors. This study may help us to understand toxicogenomics approaches utilizing array-based CGH.
참고문헌 (15)
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James, S. Brown Jr. Effects of bisphenol-A and other endocrine disruptors compared with abnormalities of schizophrenia: An endocrine-disruption theory of schizophrenia. Schizophrenia Bulletin 35:256-278 (2009)
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