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Supplementary data from "Sperm Molecular Biomarkers Are Sensitive Indicators of Testicular Injury following Subchronic Model Toxicant Exposure"


We hypothesized that sperm messenger RNA (mRNA) transcripts and DNA methylation marks can be used as translatable and sensitive indicators or testicular injury. Dose-response studies using adult male Fischer 344 rats subchronically exposed to model Sertoli cell toxicants (0.14, 0.21, and 0.33% 2,5-hexanedione, and 30, 50, and 70 mg/kg/day carbendazim), and a model germ cell toxicant (1.4, 3.4, and 5.1 mg/kg/day cyclophosphamide) for 3 months were evaluated for testicular injury by traditional histopathological endpoints, changes in sperm mRNA transcript levels using custom PCR arrays, and alterations in sperm DNA methylation via reduced representation bisulfite sequencing. Testis histopathological evaluation and PCR array analysis of the sperm transcriptome identified dose-dependent changes elicited by toxicant exposure (P < 0.05). Global sperm DNA methylation analysis of subchronic 0.33% 2,5-hexandione and 5.1 mg/kg/day cyclophosphamide exposure using a Monte Carlo approach did not identify differentially methylated regions (methylation difference > 10% and q < 0.05) with robust signatures. Overall, these results suggest that sperm mRNA transcripts are sensitive indicators of low dose toxicant-induced testicular injury in the rat, while sperm DNA methylation changes are not. Additionally, the Monte Carlo analysis is a powerful approach that can be used to assess the robustness of signals resulting from -omic studies.
This research is supported by the National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program P42ES013660

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Dere, Edward Dere, Wilson, Shelby K., Anderson, Linnea M., et al., "Supplementary data from 'Sperm Molecular Biomarkers Are Sensitive Indicators of Testicular Injury following Subchronic Model Toxicant Exposure'" (2016). Brown Superfund Data Products, Brown Superfund Project 1: Molecular Biomarkers for Assessing Testicular Toxicity Digital Archive, Brown University Open Data Collection. Brown Digital Repository. Brown University Library.