Exposure to mixture of Environmental endocrine disruptors induce miRNAs/isomiRs deregulation in mouse testis. Mus musculus

Purpose: In testis the effects of exposure to mixtures of Endocrine disruptors compounds (EDCs) upon expression of miRNAs were not addressed. Objective: To identify the expression profiles of the 'miRNome' in mice testis chronic exposed to a defined mixture of five EDCs. Methods: Pregnant mice from 0.5 post-coital day were exposed in the drinking water to a mixture containing 0.3 mg/Kg-bw/day of each phthalate (DEHP, DBP, BBP), plus 0.05 mg/Kg-bw/day of each alkylphenol (NP, OP) until adulthood of male mouse (60 days old). We characterized the 'miRNome' by next generation sequence (NGS). Results: In mouse testis exposed to EDCs mixture we detected by NGS 2 up-regulated and 8 down-regulated miRNAs along to 36 isomiRs differentially expressed; these results were validated by RT-qPCR. and functional analysis showed deregulation of testicular hormonal status, spermatogenesis disruption and germ cells apoptosis. Conclusions: Here we provide the first association between deregulation of miRNAs, isomiRs, with histopathological and hormonal alterations in adult mice testis exposed to mixture of EDCs. Overall design: Testis snc-RNA profiles of 60-day old mice of control (mice drank water only with the dose of vehicles equivalents diluted) and exposed to EDCs mixture were generated by deep sequency using MiSeq-Illumina sequencer