Daily exposure to phthalates and alkylphenols alters miR biogenesis and expression in mice ovaries

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dc.contributor.authorPatino-Garcia, Daniel
dc.contributor.authorCruz-Fernandes, Leonor
dc.contributor.authorBunay, Julio
dc.contributor.authorOrellana, Renan
dc.contributor.authorMoreno, Ricardo D.
dc.date.accessioned2025-01-23T19:47:30Z
dc.date.available2025-01-23T19:47:30Z
dc.date.issued2020
dc.description.abstractReproductive hormone imbalance in infertile women is correlated to high levels of phthalates and alkylphenols, which are among endocrine-disrupting chemicals (EDCs). Previous studies have shown that they interfere with gene expression by deregulating levels of microRNAs (miRs), small non-coding RNAs targeting mRNAs encoding enzymes in the hormone biosynthesis pathway. However, this effect depends on the target organ, dose and whether or not they are alone or in mixtures. Our goal was to study whether the biosynthesis, and a specific group of miRs targeting mRNAs encoding enzymes in steroid hormone biosynthesis, are deregulated in the ovaries of female mice chronically exposed to a mixture of three phthalates (DEHP+DBP+BBP) and two alkylphenols (NP+OP) at a human environmentally relevant dose. We performed qPCR and Western blot assays along with a bioinformatics approach and found that this mixture modified the biogenesis machinery of miRs, inducing an increase in the mRNA levels of Drosha and Dicerl and DROSHA protein levels. In addition, we found changes in the precursor and mature forms of miR-96-5p, miR-200b-3p, miR-365-3p, miR-378a-3p and miR-503-5p which target steroidogenic pathway enzymes. Finally, using primary granulosa cell culture, we confirmed that miR-200b-3p targets Cyp19a1, transcript encoding CYP19A1, the enzyme that produces estradiol (E-2). These results indicate that chronic exposure to phthalates and alkylphenols mixture alters the biogenesis of ovary miRs and increases the expression of miRs implicated in the control of steroidal hormone synthesis in female mice, thus contributing to reproductive pathologies.
dc.fuente.origenWOS
dc.identifier.doi10.1530/JME-20-0149
dc.identifier.eissn1479-6813
dc.identifier.issn0952-5041
dc.identifier.urihttps://doi.org/10.1530/JME-20-0149
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100387
dc.identifier.wosidWOS:000580551600005
dc.issue.numero4
dc.language.isoen
dc.pagina.final186
dc.pagina.inicio175
dc.revistaJournal of molecular endocrinology
dc.rightsacceso restringido
dc.subjectendocrine disruptors
dc.subjectovary
dc.subjectmiRs
dc.subjectgene regulation
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDaily exposure to phthalates and alkylphenols alters miR biogenesis and expression in mice ovaries
dc.typeartículo
dc.volumen65
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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