TY - JOUR
T1 - Insulin-like 3 affects zebrafish spermatogenic cells directly and via Sertoli cells
AU - Crespo, Diego
AU - Assis, Luiz H C
AU - Zhang, Yu Ting
AU - Safian, Diego
AU - Furmanek, Tomasz
AU - Skaftnesmo, Kai Ove
AU - Norberg, Birgitta
AU - Ge, Wei
AU - Choi, Yung-Ching
AU - den Broeder, Marjo J
AU - Legler, Juliette
AU - Bogerd, Jan
AU - Schulz, Rüdiger W
N1 - Funding Information:
The authors thank Esther Hoekman, Daniëlle Janssen, and Henk Westland for maintaining the zebrafish stocks and Henk van de Kant (all from the Science Faculty, Utrecht University, The Netherlands) for technical support, and to Chris Coomans and Dorian Luijkx for pilot studies and a literature review, respectively, in partial fulfillment of their Master thesis work at Utrecht University. This study was co-funded by the Research Council of Norway BIOTEK2021/HAVBRUK program with the projects SALMAT (n° 226221) and SALMOSTERILE (n° 221648). The authors thank the financial support provided by the Brazilian Foundation CAPES (project n° BEX:9802/12-6) and the China Scholarship Council (CSC; grant n° 201706310069), for the scholarships awarded to L.H.C.A. and Y.T.Z., respectively.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/2/15
Y1 - 2021/2/15
N2 - Pituitary hormones can use local signaling molecules to regulate target tissue functions. In adult zebrafish testes, follicle-stimulating hormone (Fsh) strongly increases the production of insulin-like 3 (Insl3), a Leydig cell-derived growth factor found in all vertebrates. Little information is available regarding Insl3 function in adult spermatogenesis. The Insl3 receptors Rxfp2a and 2b were expressed by type A spermatogonia and Sertoli and myoid cells, respectively, in zebrafish testis tissue. Loss of insl3 increased germ cell apoptosis in males starting at 9 months of age, but spermatogenesis appeared normal in fully fertile, younger adults. Insl3 changed the expression of 409 testicular genes. Among others, retinoic acid (RA) signaling was up- and peroxisome proliferator-activated receptor gamma (Pparg) signaling was down-regulated. Follow-up studies showed that RA and Pparg signaling mediated Insl3 effects, resulting in the increased production of differentiating spermatogonia. This suggests that Insl3 recruits two locally active nuclear receptor pathways to implement pituitary (Fsh) stimulation of spermatogenesis.
AB - Pituitary hormones can use local signaling molecules to regulate target tissue functions. In adult zebrafish testes, follicle-stimulating hormone (Fsh) strongly increases the production of insulin-like 3 (Insl3), a Leydig cell-derived growth factor found in all vertebrates. Little information is available regarding Insl3 function in adult spermatogenesis. The Insl3 receptors Rxfp2a and 2b were expressed by type A spermatogonia and Sertoli and myoid cells, respectively, in zebrafish testis tissue. Loss of insl3 increased germ cell apoptosis in males starting at 9 months of age, but spermatogenesis appeared normal in fully fertile, younger adults. Insl3 changed the expression of 409 testicular genes. Among others, retinoic acid (RA) signaling was up- and peroxisome proliferator-activated receptor gamma (Pparg) signaling was down-regulated. Follow-up studies showed that RA and Pparg signaling mediated Insl3 effects, resulting in the increased production of differentiating spermatogonia. This suggests that Insl3 recruits two locally active nuclear receptor pathways to implement pituitary (Fsh) stimulation of spermatogenesis.
UR - http://www.scopus.com/inward/record.url?scp=85101492969&partnerID=8YFLogxK
U2 - 10.1038/s42003-021-01708-y
DO - 10.1038/s42003-021-01708-y
M3 - Article
C2 - 33589679
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 204
ER -