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Paracrine and molecular regulation of the spermatogonial stem cell niche in zebrafish (Danio rerio) and the use of common carp (Cyprinus carpio) as a model to delay spermatogonial differentiation during puberty


Spermatogonial stem cell (SSC) niche are specific regions of the testes which regulate stem cell properties, such as, self-renewal, differentiation, apoptosis, quiescence and pluripotency. The regulation of the SSC niche is essential to avoid accumulation of SSC (seminoma), when self-renewal is favored, or spermatogenesis depletion when differentiation is predominant over self-renewal. Characterization of SSC niche and its regulation have been drawn attention of several studies, including those with teleost fish, in particular with zebrafish. Zebrafish SSC niche is formed by Sertoli cells surrounding SSC, and adjacent interstitial cells, such as Leydig cells and blood vessels. Follicle-stimulating hormone (Fsh), and growth factors, as Amh (Anti-Müllerian hormone) and Igf3 (Insulin growth factor-like) have an important role on zebrafish SSC nice. While Amh inhibits spermatogonial differentiation and maintains SSC in their undifferentiated state, being down-regulated by Fsh, Igf3, induced by Fsh, promotes differentiation and spermatogonial proliferation towards meiosis. However, it remains unclear how Amh and Igf3 interact among each other, and the molecular changes induced by them on the SSC niche. This project aims to evaluate the interaction (direct or indirect) between Amh and Igf3, and analyze in particular the global gene profile induced by Amh, in order to determine potential candidates (mRNAs or microRNAs) involved in the inhibition of the SSC differentiation in zebrafish. And finally, increasing Amh expression through transient gene transfer, the project aims to delay spermatogonial differentiation during carp puberty. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
OLIVEIRA, MARCOS A.; MARTINEZ, EMANUEL R. M.; BUTZGE, ARNO J.; DORETTO, LUCAS B.; RICCI, JULIANA M. B.; RODRIGUES, MAIRA S.; VIGOYA, ANGEL A. A.; GOMEZ-GONZALEZ, NURIA E.; STEWART, AMANDA B.; NOBREGA, RAFAEL H. Molecular characterization and expression analysis of anti-Mullerian hormone in common carp (Cyprinus carpio) adult testes. GENE EXPRESSION PATTERNS, v. 40, JUN 2021. Web of Science Citations: 0.
LACERDA, S. M. S. N.; MARTINEZ, E. R. M.; MURA, I. L. D. D.; DORETTO, L. B.; COSTA, G. M. J.; SILVA, M. A.; DIGMAYER, M.; NOBREGA, R. H.; FRANCA, L. R. Duration of spermatogenesis and identification of spermatogonial stem cell markers in a Neotropical catfish, Jundia (Rhamdia quelen). General and Comparative Endocrinology, v. 273, n. SI, p. 249-259, MAR 1 2019. Web of Science Citations: 0.
RICCI, JULIANA M. B.; MARTINEZ, EMANUEL R. M.; BUTZGE, ARNO J.; DORETTO, LUCAS B.; OLIVEIRA, MARCOS A.; BOMBARDELLI, ROBIE ALLAN; BOGERD, JAN; NOBREGA, RAFAEL H. Characterization of &ITvasa&IT homolog in a neotropical catfish, Jundia (&ITRhamdia quelen&IT): Molecular cloning and expression analysis during embryonic and larval development. Gene, v. 654, p. 116-126, MAY 15 2018. Web of Science Citations: 3.
MORAIS, R. D. V. S.; CRESPO, D.; NOBREGA, R. H.; LEMOS, M. S.; VAN DE KANT, H. J. G.; DE FRANCA, L. R.; MALE, R.; BOGERD, J.; SCHULZ, R. W. Antagonistic regulation of spermatogonial differentiation in zebrafish (Danio rerio) by Igf3 and Amh. Molecular and Cellular Endocrinology, v. 454, n. C, p. 112-124, OCT 15 2017. Web of Science Citations: 11.
CORCHUELO, SHERYLL; MARTINEZ, EMANUEL R. M.; BUTZGE, ARNO J.; DORETTO, LUCAS B.; RICCI, JULIANA M. B.; VALENTIN, FERNANDA N.; NAKAGHI, LAURA S. O.; SOMOZA, GUSTAVO M.; NOBREGA, RAFAEL H. Characterization of Gnrh/Gnih elements in the olfacto-retinal system and ovary during zebrafish ovarian maturation. Molecular and Cellular Endocrinology, v. 450, n. C, p. 1-13, JUL 15 2017. Web of Science Citations: 12.

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