The complex control of terminal cell differentiation to produce gameta is mediated by mechanisms of gene expression regulation interacting with multiple endocrine, paracrine and autocrine factors.
Our laboratory focuses on the study of molecular mechanisms that, trough differential gene expression of both mRNAs and sRNAs (small RNAs), controling the development of oocytes, spermatozoa and early postzygotic stages.
In mammals, differentiation of germ cells starts in the fetal period, progressing in various stages of postnatal life. This requires a high level of molecular and cellular coordination, regulated by differential gene expression. Our group studies the role and regulation of genes involved in gametogenesis in both sexes and their contribution to zygotic preimplantation development and how their deregulation can be potentially responsible for impaired fertility. In this sense, one of our current interest is to identify mechanisms of action, at genetic, epigenetic and cellular level, potentially caused by environmental contaminants compounds able to induce reproductive disorders. Using mouse as experimental model and various approaches such as: high-density DNA microarrays, deep sequencing of RNAs, cell analysis or null mutant mouse models for specific genes, we are studying functional gene regulatory expression and genetic networks during development of different gametogenic cell types from primordial germ cells (PGCs) to mature gametes. In addition to the normal patterns of gene expression, we are studying the effects of various compounds considered as reprotoxicants in relation to their level or period of exposure during development, both during the gametogenesis of individuals directly exposed as possible transgenerational effects associated with epigenetic mechanisms.
Our group is particularly focussed on the study of biogenesis and functional role of regulatory noncoding small RNAs, specifically microRNAs endo-siRNAs and piRNAs ( previously defined as germline specific) and their action as post-transcriptional regulators, both in gametogenesis and in preimplantation zygotes.
García-López, J., Larriba E. and J. del Mazo . Detection and characterization of small non-coding RNAs in mouse gametes and embryos prior to zygotic genome activation. In: Zygotic Genome Activation: Methods and Protocols. Methods in Molecular Biology. Editor: Kiho Lee. Springer. New York, NY 10013, U
Buñay J., Larriba E., Moreno R., and J. del Mazo . Chronic low-dose exposure to a mixture of environmental endocrine disruptors induces microRNAs/isomiRs deregulation in mouse concomitant with intratesticular estradiol reduction. Scientific Reports 7: 3373
Buñay J., Larriba E., Patiño D., Cruz-Fernandes L., Castañeda S., Morales C., Jesús del Mazo* and Moreno R.D* (*equal contribution) . Differential Effects of Exposure to Single versus a Mixture of Endocrine-Disrupting Chemicals on Steroidogenesis Pathway in Mouse Testes. Toxicological Sciences. (Advance Access Publication Date: September 22, 2017))
J. Isoler-Alcaraz, D. Fernández-Pérez, E. Larriba and J. del Mazo . Cellular and molecular characterization of gametogenic progression in ex vivo cultured prepuberal mouse testes. Reproductive Biology and Endocrinology 15:85
E. Larriba, J.del Mazo . Role of Non-Coding RNAs in the Transgenerational Epigenetic Transmission of the Effects of Reprotoxicants. Int J Mol Sci. 2016 Mar 25;17(4)
Brieño-Enríquez M.A., Larriba E. and J. del Mazo . Endocrine disrupters, microRNAs and primordial germ cells: a dangerous cocktail. Fertility and Sterility 106:871–879
García-López J., Alonso L., Cárdenas D.B., Artaza-Alvarez H, Hourcade J.de D., Martinez S., Brieño-Enríquez M. A., and del Mazo J . Diversity and functional convergence of small non-coding RNAs in male germ cell differentiation and fertilization. RNA, 21:946–962
Miguel A. Brieño-Enríquez, Jesús García-López, David B. Cárdenas, Sylvain Guibert, Elouan Cleroux, Lukas Děd, Juan de Dios Hourcade, Jana Pěknicová, Michael Weber, Jesús del Mazo . Exposure to Endocrine Disruptor Induces Transgenerational Epigenetic Deregulation of MicroRNAs in Primordial Germ Cells. PLoS ONE 10(4): e0124296. doi:10.1371/journal.pone.0124296
García-López J., Hourcade JdD, Alonso L., Cárdenas D.B. and del Mazo J . Global characterization and target identification of piRNAs and endo-siRNAs in mouse gametes and zygotes” BBA-Gene Regulatory Mechanisms. 1839:463-475 (2014)
Jesús del Mazo, Jesús García-López, and Michael Weber . Epigenetic traits of testicular cancer: from primordial germ cells to germ cell tumors. Epigenomics, June 2014, Vol. 6, No. 3 , Pages 253-255
“Reprogramming of DNA methylation during mammalian development and environmental impact of endocrine disruptors”. Grant Agency: CEFIC-LRI. CEFIC (European Chemical Industry Council) Long-range Research Inititative [joining chemical industry associations ACC USA), JCIA (Japan) and CEFIC (Europe)].
“Análisis funcional de microRNAs (miRNAs) en embriogénesis temprana de mamíferos” FIS (MICIN) (PI071007).
"Identification of genetic biomarkers of transgenerational effects of Endocrine Disruptor compounds on the mouse germ cells development”CSIC-ASCR (Czech Republic) (2008CZ0014).
“Análisis funcional de microRNAs en gametogénesis y estadios postcigóticos preimplantacionales”. CSIC (201020E016) 2010-2012.
"Impact of Endocrine Disruptors on genomic DNA methylation patterns in the germline”.Programme National de Recherche sur les Perturbateurs Endocriniens” Ministère de l’Ecologie, du Developpment Durable, des Transports et du Logement. República Francesa.(11-MRES-PNRPE-9-CVS-072-Nº210064934).2012-2014
“Efectos transgeneracionales de disruptores endocrinos ambientales mediados por RNAs pequeños no-codificantes sobre células germinales primordiales” MINECO (BFU2013-42164-R). 2014-2017
- In March 2009 the European Commission appointed Jesús del Mazo as member of the "Scientific Advisors on Risk Assessment and Public Health" (Commission Decision 2008/721/EC).
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