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In reproductive tissues, microRNAs (miRNAs) are emerging as key targets of EDCs. Here, we analysed changes in the testis \u201cmiRNome\u201d (and their biogenesis mechanism) in chronically exposed adult mice to a cocktail of five EDCs containing 0.3\u2009mg\/kg-body weight (BW)\/day of each phthalate (DEHP, DBP, BBP) and 0.05\u2009mg\/kg-BW\/day of each alkylphenol (NP, OP), from conception to adulthood. The testis \u201cmiRNome\u201d was characterised using next-generation sequencing (NGS). Expression levels of genes involved in miRNA biogenesis were measured by RT-qPCR, as well as several physiological and cytological parameters. We found two up-regulated, and eight down-regulated miRNAs and thirty-six differentially expressed isomiRs along with an over-expression of<jats:italic>Drosha<\/jats:italic>,<jats:italic>Adar<\/jats:italic>and<jats:italic>Zcchc11<\/jats:italic>. A significant decrease of intratesticular estradiol but not testosterone was detected. Functional analysis showed altered spermatogenesis, germ cell apoptosis and negative correlation of<jats:italic>miR-18a-5p<\/jats:italic>with<jats:italic>Nr1h2<\/jats:italic>involved in the deregulation of the steroidogenesis pathway. Here, we present the first association between miRNA\/isomiRs deregulation, their mechanisms of biogenesis and histopathological and hormonal alterations in testes of adult mice exposed to a mixture of low-dose EDCs, which can play a role in male infertility.<\/jats:p>","DOI":"10.1038\/s41598-017-02752-7","type":"journal-article","created":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T10:55:56Z","timestamp":1496832956000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs\/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction"],"prefix":"10.1038","volume":"7","author":[{"given":"Julio","family":"Bu\u00f1ay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-4974","authenticated-orcid":false,"given":"Eduardo","family":"Larriba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo D.","family":"Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"del Mazo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,13]]},"reference":[{"key":"2752_CR1","unstructured":"Damstra, T., Barlow, S., Bergman, A., Kavlock, R. & Van Der Kraak, G. 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