| Yazarlar |
Dr. Öğr. Üyesi Ferhat ULU
Kastamonu Üniversitesi, Türkiye |
Sung-Min Kim
|
|
Toshifumi Yokoyama
|
|
Yukiko Yamazaki
|
| Özet |
| Male differentiation of primordial germ cells (PGCs) is initiated by the inhibition of entry into meiosis and exposure to male-inducing factor(s), which are regulated by somatic elements of the developing gonad. Fibroblast growth factor 9 (FGF9) produced by pre-Sertoli cells is essential for male gonadal differentiation and also contributes to survival and male differentiation of XY PGCs. However, it is not clear how FGF9 regulates PGC fate. Using a PGC culture system, we identified dose-dependent, fate-determining functions of FGF9 in XY PGCs. Treatment with low levels of FGF9 (0.2 ng/ml) increased expression of male-specific Dnmt3L and Nanos2 in XY PGCs. Conversely, treatment with high levels of FGF9 (25 ng/ml) suppressed male-specific gene expression and stimulated proliferation of XY PGCs. Western blotting showed that low FGF9 treatment enhanced p38 MAPK (mitogen-activated protein kinase) phosphorylation in the same cells. In contrast, high FGF9 treatment significantly stimulated the ERK (extracellular signal-regulated kinase)1/2 signaling pathway in XY PGCs. We investigated the relationship between the ERK1/2 signaling pathway stimulated by high FGF9 and regulation of PGC proliferation. An ERK1/2 inhibitor (U0126) suppressed the PGC proliferation that would otherwise be stimulated by high FGF9 treatment, and increased Nanos2 expression in XY PGCs. Conversely, a p38 MAPK inhibitor (SB202190) significantly suppressed Nanos2 expression that would otherwise be stimulated by low FGF9 in XY PGCs. Taken together, our results suggest that stage-specific expression of FGF9 in XY gonads regulates the balance between proliferation and differentiation of XY PGCs in a dose-dependent manner. |
| Anahtar Kelimeler |
| Cell proliferation | ERK1/2 signaling pathway | FGF9 | Male differentiation | P38 signaling pathway | XY primordial germ cells |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale |
| Dergi Adı | BIOLOGY OF REPRODUCTION |
| Dergi ISSN | 0006-3363 |
| Dergi Tarandığı Indeksler | SCI |
| Makale Dili | İngilizce |
| Basım Tarihi | 01-2017 |
| Cilt No | 96 |
| Sayı | 1 |
| Sayfalar | 122 / 133 |
| Doi Numarası | 10.1095/biolreprod.116.143941 |
| Makale Linki | https://academic.oup.com/biolreprod/article/96/1/122/2734431?login=true |
| Atıf Sayıları | |
| WoS | 8 |
| SCOPUS | 9 |
| Google Scholar | 10 |
