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Researchers identify novel function of spermatogonial stem cells’ self-renewal factor



Researchers have discovered a novel function of fibroblast growth factor 2 (FGF2), a self-renewal factor for spermatogonial stem cell (SSC), which is the origin of sperm production.

Both FGF2 and glial cell line-derived neurotrophic factor (GDNF) are known to be indispensable for SSC self-renewal and survival in vitro, but the present study revealed that FGF2 showed different properties from GDNF in mouse testis. Seiji Takashima, Ph.D., an assistant professor of Textile Science and Technology at Shinshu University and corresponding author on the paper, successfully identified a novel function of FGF2 in mouse testis using a "biodegradable gelatin microsphere system" capable of sustained diffusion of self-renewal factors for several days in vivo.

This finding, published in the June issue of Stem Cell Reports, will contribute to the regulation of SSCs in vivo for the treatment of male infertility.

Consecutive production of sperm is ensured by the repeat of self-renewal and differentiation of SSCs. It was well known that the self-renewal of SSCs is promoted by GDNF, while retinoic acid (RA) induces the differentiation toward sperm production. In 2015, Dr. Takashima found that FGF2 also acts as a self-renewal factor for SSCs in vitro. In this latest study, his group demonstrated that FGF2 conversely acts as a differentiation promoting factor in vivo.


They found that FGF2-stimulated SSCs frequently expressed a receptor for RA when compared to those stimulated by GDNF, suggesting that FGF2 expands differentiation-susceptible subset of SSCs. Simultaneously, they also demonstrated that this molecule acts on a testicular microenvironment, which is required for SSC function, to facilitate RA action. These results demonstrate that FGF2, which was shown to be a “bona fide self-renewal factor for SSCs in vitro” in 2015, can conversely act to facilitate SSC differentiation in vivo. Considering that GDNF/FGF2 ratio shows dynamic change during testicular development and regeneration, the functional balance between GDNF and FGF2 might play a pivotal role in the regulation of sperm production from SSCs.

The finding will contribute not only to understanding the principle of sperm production, but also to future applications for male infertility treatment, breeding live stock and conservation of endangered species.

FGF2 expands RARG expressing subset of SSCs FGF2 facilitates RA action toward proper spermatogenesis. Image courtesy of Seiji Takashima Ph.D., the Faculty of Textile Science and Technology, Shinshu University. 

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DOI: 10.1016/j.stemcr.2018.03.016