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Retinoic acid-stimulated ERK1/2 pathway regulates meiotic initiation in cultured fetal germ cells        
Yazarlar
Sung Mın Kım
Toshıfumı Yokoyama
Dylan Ng
Dr. Öğr. Üyesi Ferhat ULU Dr. Öğr. Üyesi Ferhat ULU
Kastamonu Üniversitesi, Türkiye
Yukıko Yamazakı
Özet
In murine fetal germ cells, retinoic acid (RA) is an extrinsic cue for meiotic initiation that stimulates transcriptional activation of the Stimulated by retinoic acid gene 8 (Stra8), which is required for entry of germ cells into meiotic prophase I. Canonically, the biological activities of RA are mediated by nuclear RA receptors. Recent studies in somatic cells found that RA noncanonically stimulates intracellular signal transduction pathways to regulate multiple cellular processes. In this study, using a germ cell culture system, we investigated (1) whether RA treatment activates any mitogen-activated protein kinase (MAPK) pathways in fetal germ cells at the time of sex differentiation, and (2) if this is the case, whether the corresponding RA-stimulated signaling pathway regulates Stra8 expression in fetal germ cells and their entry into meiosis. When XX germ cells at embryonic day (E) 12.5 were cultured with RA, the extracellular-signal-regulated kinase (ERK) 1/2 pathway was predominantly activated. MEK1/2 inhibitor (U0126) treatment suppressed the mRNA expressions of RA-induced Stra8 and meiotic marker genes (Rec8, Spo11, Dmc1, and Sycp3) in both XX and XY fetal germ cells. Furthermore, U0126 treatment dramatically reduced STRA8 protein levels and numbers of meiotic cells among cultured XX and XY fetal germ cells even in the presence of RA. Taken together, our results suggest the novel concept that the RA functions by stimulating the ERK1/2 pathway and that this activity is critical for Stra8 expression and meiotic progression in fetal germ cells.
Anahtar Kelimeler
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı PLOS ONE
Dergi ISSN 1932-6203
Dergi Tarandığı Indeksler SCI
Dergi Grubu Q2
Makale Dili İngilizce
Basım Tarihi 11-2019
Cilt No 14
Sayı 11
Sayfalar 224628 / 0
Doi Numarası 10.1371/journal.pone.0224628
Makale Linki http://dx.plos.org/10.1371/journal.pone.0224628