Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Testicular cancer, currently the most common cancer affecting men of reproductive age, is one of the most curable malignancies due to the progress made in the early diagnosis and effective treatment of this disease. The coadministration of bleomycin, etoposide, and cis-platinum (BEP) has brought the 5-yr survival rate of testis cancer patients to over 90%. However, this treatment results in reproductive chemotoxic effects. We assessed the effect of BEP treatment on sperm chromatin integrity and sperm head protein profiles of adult male Brown Norway rats following 9 wk of treatment with BEP and in animals treated for 9 wk and then subjected to a 9-wk recovery period. Both the susceptibility of DNA to denaturation and the number of strand breaks were significantly increased in mature sperm following 9 wk of treatment with BEP; proteomic analysis revealed that the expression of several proteins, including HSP90AA1 and HSP90B1, was markedly affected. Following a 9-wk recovery period, mature sperm did not show significant DNA damage, indicating that repair had potentially occurred. Interestingly, the protamination level of the sperm of these animals was significantly decreased, while histones HIST1H1D (H1.2), HIST1H4B (H4), HIST2H2AA3 (H2A1), and HIST1H2BA (H2B1A) were concomitantly up-regulated; this was not observed in the sperm immediately following 9 wk of treatment. Thus, there are persistent effects on proteins in sperm heads from the cauda epididymidis 9 wk posttreatment, in the absence of DNA strand breaks. We suggest that these effects on the sperm head proteome may contribute to long-lasting adverse effects in the progeny of BEP-exposed males.
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PMID:Exposure to bleomycin, etoposide, and cis-platinum alters rat sperm chromatin integrity and sperm head protein profile. 2240 60

Treatment of testicular cancer includes the coadministration of bleomycin, etoposide and cis-platinum (BEP); however, along with its therapeutic benefit, BEP exposure results in extensive reproductive chemotoxic effects, including alterations to sperm chromatin integrity. As an intact paternal genome is essential for successful fertilization and embryogenesis, we assessed the effect of paternal exposure to BEP on sperm fertilization capacity and the resulting consequences on early embryonic gene expression. Adult male Brown Norway rats received a 9-week treatment with BEP or saline and then were sacrificed immediately or subject to a 9-week recovery period. HSP90AA1, HSP90B1 and PDIA3, involved in spermatozoa-egg interactions, were overexpressed in BEP-exposed spermatozoa after the 9-week treatment period; overexpression was also observed in spermatozoa from BEP-treated rats after 9 weeks of recovery. These proteins were localized to the plasma membrane of the sperm head; this localization may facilitate their role in spermatozoa-egg interactions as the highest staining intensities were observed in capacitated spermatozoa. The fertilization potential of spermatozoa was determined by in vitro fertilization with oocytes from unexposed naturally cycling female rats. Interestingly, the fertilization potential of spermatozoa following a 9-week recovery period from BEP treatment was significantly enhanced compared with controls. Moreover, stem cell transcription factors, involved in the regulation of a plethora of early embryonic events, were upregulated by more than twofold in eight-cell stage embryos sired by BEP recovery males compared with controls; this suggests that there are potential deleterious effects on embryo development well after termination of BEP exposure.
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PMID:Paternal exposure to testis cancer chemotherapeutics alters sperm fertilizing capacity and affects gene expression in the eight-cell stage rat embryo. 2447 30