RGD Reference Report - Paternal exposure to testis cancer chemotherapeutics alters sperm fertilizing capacity and affects gene expression in the eight-cell stage rat embryo. - Rat Genome Database

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Paternal exposure to testis cancer chemotherapeutics alters sperm fertilizing capacity and affects gene expression in the eight-cell stage rat embryo.

Authors: Maselli, J  Hales, BF  Robaire, B 
Citation: Maselli J, etal., Andrology. 2014 Mar;2(2):259-66. doi: 10.1111/j.2047-2927.2014.00185.x. Epub 2014 Jan 29.
RGD ID: 10445831
Pubmed: PMID:24478030   (View Abstract at PubMed)
DOI: DOI:10.1111/j.2047-2927.2014.00185.x   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to xenobiotic stimulus  IEP 10445831; 10445831bleomycin more ...RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
sperm flagellum  IDA 10445831 RGD 
sperm head plasma membrane  IDA 10445831 RGD 
sperm mitochondrial sheath  IDA 10445831 RGD 
sperm plasma membrane  IDA 10445831 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hsp90aa1  (heat shock protein 90 alpha family class A member 1)
Hsp90ab1  (heat shock protein 90 alpha family class B member 1)


Additional Information