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Exposure to Endocrine Disruptor Induces Transgenerational Epigenetic Deregulation of MicroRNAs in Primordial Germ Cells
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SYSNO ASEP 0445129 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Exposure to Endocrine Disruptor Induces Transgenerational Epigenetic Deregulation of MicroRNAs in Primordial Germ Cells Author(s) Brieno-Enriguez, M. A. (ES)
García-López, J. (ES)
Cárdenas, D.B. (ES)
Guibert, S. (FR)
Cleroux, E. (FR)
Děd, Lukáš (BTO-N) RID
de Dios Hourcade, J. (ES)
Pěknicová, Jana (BTO-N) RID
Weber, M. (FR)
del Mazo, J. (ES)Number of authors 10 Source Title PLoS ONE. - : Public Library of Science - ISSN 1932-6203
Roč. 10, č. 4 (2015)Number of pages 19 s. Language eng - English Country US - United States Keywords endocrine disruptor ; epigenetics ; primordial germ cells ; vinclozolin ; TUNEL analysis ; methylation Subject RIV EB - Genetics ; Molecular Biology R&D Projects GAP503/12/1834 GA ČR - Czech Science Foundation (CSF) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support BTO-N - RVO:86652036 UT WOS 000353212600061 DOI 10.1371/journal.pone.0124296 Annotation In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs) during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2016
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