Data from: Small RNAs in rat sperm are a predictive and sensitive biomarker of exposure to the testicular toxicant ethylene glycol monomethyl ether.
Stermer, Angela R., Brown University
Reyes, Gerardo, Brown University
Hall, Susan J., Brown University
Boekelheide, Kim, Brown University
Published Feb 13, 2019 on Dryad.
Cite this dataset
Stermer, Angela R.; Reyes, Gerardo; Hall, Susan J.; Boekelheide, Kim (2019). Data from: Small RNAs in rat sperm are a predictive and sensitive biomarker of exposure to the testicular toxicant ethylene glycol monomethyl ether. [Dataset]. Dryad. https://doi.org/10.5061/dryad.30010gs
Testicular histology and semen parameters are considered the gold standards when determining male reproductive toxicity. Ethylene glycol monomethyl ether (EGME) is a testicular toxicant with well-described effects on histopathology and sperm parameters. To compare the predictivity and sensitivity of molecular biomarkers of testicular toxicity to the traditional endpoints, small RNAs in the sperm were analyzed by next generation RNA-sequencing (RNA-seq). Adult rats were exposed to 0, 50, 60, or 75 mg/kg EGME by oral gavage for 5 consecutive days. Testis histology, epididymal sperm motility and sperm small RNAs, including microRNAs (miRNAs), mRNA fragments, piwi-associated RNAs (piRNAs), and tRNA fragments (tRFs), were analyzed 5 weeks after cessation of exposure. Testicular histology showed a significant dose-dependent increase in retained spermatid heads (RSH), while sperm motility declined with increasing dose. RNA-seq of sperm small RNAs was used to identify significant dose-dependent changes in percent mRNA fragments (of total reads), percent miRNAs (of total reads), average tRF length, average piRNA length, and piRNA and tRF length-distributions. Discriminant analysis showed relatively low predictivity of treatment based on RSH or motility compared to the average read length of all aligned RNAs. Benchmark dose (BMD) modeling resulted in a BMD of 62 mg/kg using RSH, whereas average read length of all aligned RNAs resulted in a BMD of 47 mg/kg. These results showed that sperm small RNAs are sensitive and predictive biomarkers of EGME-induced male reproductive toxicity.
Supplemental Figures for Stermer et al.
Supplemental Figures include a photomicrograph from a sperm motility video of sperm collected from a 100 mg/kg treated rat in a preliminary EGME dose-response experiement, and the best-fit BMD curves of the z-transformed data for normally distributed endpoints measured after EGME exposure.
Supplemental Tables for Stermer et al.
Supplemental Tables include BMD modeling summary for the z-transformed data of normally distributed endpoints after EGME exposure, and a summary of the coeffecient of variance for each of these endpoints.