Skip Navigation

Final Progress Reports: Brown University: Testicular Sensitization and Co-Exposure Synergy

Superfund Research Program

Testicular Sensitization and Co-Exposure Synergy

Project Leader: Kim Boekelheide
Grant Number: P42ES013660
Funding Period: 2005-2009

Project-Specific Links

Connect with the Grant Recipients

Visit the grantee's eNewsletter page Visit the grantee's eNewsletter page Visit the grantee's Twitter page Visit the grantee's Facebook page Visit the grantee's Video page

Final Progress Reports

Year:   2008 

The testis is an important target organ for chemical-induced toxicity. Little is known at the mechanistic or practical level about the effects of complex exposures on the testis. This research project seeks to understand how exposure to one testicular toxicant alters the susceptibility of the testis to injury by a second testicular toxicant, and to develop sperm biomarkers of low dose testicular toxicant exposure. This is highly relevant to hazardous chemical sites, where complex exposures are the norm.

Having previously documented the histopathologic changes and performed microarrays to evaluate the gene expression response following single and combined exposures to model testicular toxicants, this year has been devoted to addressing the large bioinformatics task of evaluating this dataset. A team, consisting of two biostatisticians (Drs. Andy Houseman and Jean Wu), a biostatistics graduate student (Ms. Yunxia Sui), and a postdoctoral fellow (Dr. Sarah Campion) has been working to analyze interactions between the toxicants. The preliminary set of results for pathway analysis looks very promising, identifying pathways as significant that make sense and are biologically relevant to the researcher’s model. This work will continue, and promises to produce both novel statistical approaches to the analysis of mixture exposures and new biological insight into toxicant interactions within the testis.

Also underway is the use of rat models to develop sperm biomarkers of effect for low dose exposures to model testicular toxicants. The model toxicants are 2,5-hexanedione, a Sertoli cell toxicant, and 1,2-dibromo-3-chloropropane, a germ cell toxicant. To date, methods have been developed to isolate both mRNA and DNA from epididymal sperm with the goal of performing microarrays and analyses for DNA methylation (epigenetic modification) on the same samples.

Back
to Top