Journal
JOURNAL OF REPRODUCTION AND DEVELOPMENT
Volume 64, Issue 3, Pages 267-275Publisher
SOCIETY REPRODUCTION & DEVELOPMENT-SRD
DOI: 10.1262/jrd.2018-015
Keywords
Fibroblast growth factor 2 (FGF2); Germline niche; Glial cell line-derived neurotrophic factor (GDNF); Self-renewal; Spermatogonial stem cell (SSC)
Funding
- JSPS KAKENHI [JP16H05046]
- Sumitomo Foundation
- Naito Foundation
- Ito Foundation
- Hokuto Foundation for Bioscience
- Japan Health Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
- Uehara Memorial Foundation
- Suzuken Memorial Foundation
- Takeda Science Foundation
- Foundation of Nagano Prefecture Science Promotion
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Glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2) are bona fide self renewal factors for spermatogonial stem cells (SSCs). Although GDNF is indispensable for the maintenance of SSCs, the role of FGF2 in the testis remains to be elucidated. To clarify this, the expression dynamics and regulatory mechanisms of Fgf2 and Gdnf in the mouse testes were analyzed. It is well known that Sertoli cells express Gdnf, and its receptor is expressed in a subset of undifferentiated spermatogonia, including SSCs. However, we found that Fgf2 was mainly expressed in the germ cells and its receptors were expressed not only in the cultured spermatogonial cell line, but also in testicular somatic cells. Aging, hypophysectomy, retinoic acid treatment, and testicular injury induced distinct Fgf2 and Gdnf expression dynamics, suggesting a difference in the expression mechanism of Fgf2 and Gdnf in the testis. Such differences might cause a dynamic fluctuation of Gdnf/Fgf2 ratio depending on the intrinsic/extrinsic cues. Considering that FGF2-cultured spermatogonia exhibit more differentiated phenotype than those cultured with GDNF, FGF2 might play a role distinct from that of GDNF in the testis, despite the fact that both factors are self-renewal factor for SSC in vitro.
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