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Stem Cell Reports. 2018 Jun 5;10(6):1782-1792. doi: 10.1016/j.stemcr.2018.03.016. Epub 2018 Apr 19.

FGF2 Has Distinct Molecular Functions from GDNF in the Mouse Germline Niche.

Author information

1
Department of Textile Science and Technology, Interdisciplinary Graduate School of Science and Technology, Shinshu University, 3-15-1 Tokida, Ueda 386-8567, Japan.
2
Department of Applied Biology, Faculty of Textile Science and Technology, Shinshu University, Ueda 386-8567, Japan.
3
Division of Epigenome Dynamics, Institute of Advanced Medical Sciences, Tokushima University, Tokushima 770-8501, Japan.
4
Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
5
Nagano Animal Industry Experiment Station, Shiojiri 399-0711, Japan.
6
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
7
Department of Urology, Nagano Red Cross Hospital, Nagano 380-8582, Japan.
8
Department of Urology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
9
Department of Textile Science and Technology, Interdisciplinary Graduate School of Science and Technology, Shinshu University, 3-15-1 Tokida, Ueda 386-8567, Japan; Department of Applied Biology, Faculty of Textile Science and Technology, Shinshu University, Ueda 386-8567, Japan.
10
Department of Textile Science and Technology, Interdisciplinary Graduate School of Science and Technology, Shinshu University, 3-15-1 Tokida, Ueda 386-8567, Japan; Department of Applied Biology, Faculty of Textile Science and Technology, Shinshu University, Ueda 386-8567, Japan. Electronic address: stakashi@shinshu-u.ac.jp.

Abstract

Both glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2) are bona fide self-renewal factors for spermatogonial stem cells, whereas retinoic acid (RA) induces spermatogonial differentiation. In this study, we investigated the functional differences between FGF2 and GDNF in the germline niche by providing these factors using a drug delivery system in vivo. Although both factors expanded the GFRA1+ subset of undifferentiated spermatogonia, the FGF2-expanded subset expressed RARG, which is indispensable for proper differentiation, 1.9-fold more frequently than the GDNF-expanded subset, demonstrating that FGF2 expands a differentiation-prone subset in the testis. Moreover, FGF2 acted on the germline niche to suppress RA metabolism and GDNF production, suggesting that FGF2 modifies germline niche functions to be more appropriate for spermatogonial differentiation. These results suggest that FGF2 contributes to induction of differentiation rather than maintenance of undifferentiated spermatogonia, indicating reconsideration of the role of FGF2 in the germline niche.

KEYWORDS:

fibroblast growth factor 2; germline niche; glial cell line-derived neurotrophic factor; retinoic acid; spermatogonial differentiation; spermatogonial self-renewal

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