Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction

Abstract Humans are environmentally exposed not only to single endocrine-disrupting chemicals (EDCs) but to mixtures that affect their reproductive health. In reproductive tissues, microRNAs (miRNAs) are emerging as key targets of EDCs. Here, we analysed changes in the testis “miRNome” (and their bi...

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Autores principales:	Julio Buñay, Eduardo Larriba, Ricardo D. Moreno, Jesús del Mazo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a5c231269c743b785c790d876385a34
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spelling	oai:doaj.org-article:1a5c231269c743b785c790d876385a342021-12-02T16:06:49ZChronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction10.1038/s41598-017-02752-72045-2322https://doaj.org/article/1a5c231269c743b785c790d876385a342017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02752-7https://doaj.org/toc/2045-2322Abstract Humans are environmentally exposed not only to single endocrine-disrupting chemicals (EDCs) but to mixtures that affect their reproductive health. In reproductive tissues, microRNAs (miRNAs) are emerging as key targets of EDCs. Here, we analysed changes in the testis “miRNome” (and their biogenesis mechanism) in chronically exposed adult mice to a cocktail of five EDCs containing 0.3 mg/kg-body weight (BW)/day of each phthalate (DEHP, DBP, BBP) and 0.05 mg/kg-BW/day of each alkylphenol (NP, OP), from conception to adulthood. The testis “miRNome” 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 Drosha, Adar and Zcchc11. A significant decrease of intratesticular estradiol but not testosterone was detected. Functional analysis showed altered spermatogenesis, germ cell apoptosis and negative correlation of miR-18a-5p with Nr1h2 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.Julio BuñayEduardo LarribaRicardo D. MorenoJesús del MazoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julio Buñay Eduardo Larriba Ricardo D. Moreno Jesús del Mazo Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction
description	Abstract Humans are environmentally exposed not only to single endocrine-disrupting chemicals (EDCs) but to mixtures that affect their reproductive health. In reproductive tissues, microRNAs (miRNAs) are emerging as key targets of EDCs. Here, we analysed changes in the testis “miRNome” (and their biogenesis mechanism) in chronically exposed adult mice to a cocktail of five EDCs containing 0.3 mg/kg-body weight (BW)/day of each phthalate (DEHP, DBP, BBP) and 0.05 mg/kg-BW/day of each alkylphenol (NP, OP), from conception to adulthood. The testis “miRNome” 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 Drosha, Adar and Zcchc11. A significant decrease of intratesticular estradiol but not testosterone was detected. Functional analysis showed altered spermatogenesis, germ cell apoptosis and negative correlation of miR-18a-5p with Nr1h2 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.
format	article
author	Julio Buñay Eduardo Larriba Ricardo D. Moreno Jesús del Mazo
author_facet	Julio Buñay Eduardo Larriba Ricardo D. Moreno Jesús del Mazo
author_sort	Julio Buñay
title	Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction
title_short	Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction
title_full	Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction
title_fullStr	Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction
title_full_unstemmed	Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction
title_sort	chronic low-dose exposure to a mixture of environmental endocrine disruptors induces micrornas/isomirs deregulation in mouse concomitant with intratesticular estradiol reduction
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1a5c231269c743b785c790d876385a34
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Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction

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