Environmentally Induced Sperm RNAs Transmit Cancer Susceptibility to Offspring in a Mouse Model [RNA-seq]

Our study revealed that miRNAs constituted the main small RNA subtype altered by DDT exposure, with a specific DDT-induced surge in sperm miRNA-10b. This miRNA, along with other members of the miRNA-10 family, plays a critical role in embryonic development and cell differentiation through the regulation of Homeobox (Hox) and other genes. Interestingly, studies examining different paternal environmental exposures including obesity and malnutrition report a upregulation of miRNA-10b and other members of the miR-10 family in sperm. It has also been reported that both sperm miRNA-10a and miRNA-10b are conserved across species including humans. These miRNAs are acquired by sperm cells during epididymal transit in mice, suggesting that alterations in this family could potentially act as a “sensor” of paternal environments. Overall design: To further validate the functional importance of miRNA-10b to phenotypes observed in DDT offspring, we injected synthetic miR-10b (or control scramble-miR or vehicle solution) into normal mouse zygotes. Injected embryos were then transferred into surrogate dams to generate the miR-10b and CO offspring