| Full text | |
| Author(s): Show less - |
Doretto, Lucas B.
;
Butzge, Arno J.
;
Nakajima, Rafael T.
;
Martinez, Emanuel R. M.
;
de Souza, Beatriz Marques
;
Rodrigues, Maira da Silva
;
Rosa, Ivana F.
;
Ricci, Juliana M. B.
;
Tovo-Neto, Aldo
;
Costa, Daniel F.
;
Malafaia, Guilherme
;
Shao, Changwei
;
Nobrega, Rafael H.
Total Authors: 13
|
| Document type: | Journal article |
| Source: | CELLS; v. 11, n. 8, p. 27-pg., 2022-04-01. |
| Abstract | |
Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GDNF Family Receptor alpha 1-GFR alpha 1) are well known to mediate spermatogonial stem cell (SSC) proliferation and survival in mammalian testes. In nonmammalian species, Gdnf and Gfr alpha 1 orthologs have been found but their functions remain poorly investigated in the testes. Considering this background, this study aimed to understand the roles of the Gdnf-Gfr alpha 1 signaling pathway in zebrafish testes by combining in vivo, in silico and ex vivo approaches. Our analysis showed that zebrafish exhibit two paralogs for Gndf (gdnfa and gdnfb) and its receptor, Gfr alpha 1 (gfr alpha 1a and gfr alpha 1b), in accordance with a teleost-specific third round of whole genome duplication. Expression analysis further revealed that both ligands and receptors were expressed in zebrafish adult testes. Subsequently, we demonstrated that gdnfa is expressed in the germ cells, while Gfr alpha 1a/Gfr alpha 1b was detected in early spermatogonia (mainly in types A(und) and A(diff)) and Sertoli cells. Functional ex vivo analysis showed that Gdnf promoted the creation of new available niches by stimulating the proliferation of both type A(und) spermatogonia and their surrounding Sertoli cells but without changing pou5f3 mRNA levels. Strikingly, Gdnf also inhibited late spermatogonial differentiation, as shown by the decrease in type B spermatogonia and down-regulation of dazl in a co-treatment with Fsh. Altogether, our data revealed that a germ cell-derived factor is involved in maintaining germ cell sternness through the creation of new available niches, supporting the development of spermatogonial cysts and inhibiting late spermatogonial differentiation in autocrine- and paracrine-dependent manners. (AU) | |
| FAPESP's process: | 17/08274-3 - ZEBRAFISH (Danio rerio) SPERMATOGONIAL CELL TRANSCRIPTOME UNDER INFLUENCE OF THE FOLLICLE-STIMULATING HORMONE (FSH) |
| Grantee: | Lucas Benites Doretto |
| Support Opportunities: | Scholarships abroad - Research Internship - Master's degree |
| FAPESP's process: | 14/07620-7 - Spermatogonial stem cell bank to preserve the genotype of endangered and valuable teleost species |
| Grantee: | Rafael Henrique Nóbrega |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 16/12101-4 - Selection, Culture and Transcriptome of spermatogonial stem cells of zebrafish, Danio rerio: a functional and genomics approach |
| Grantee: | Lucas Benites Doretto |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 20/03569-8 - Testicular organoids and novel in vitro approaches to study spermatogonial stem cells and spermatogenesis in fish |
| Grantee: | Rafael Henrique Nóbrega |
| Support Opportunities: | Regular Research Grants |