title: Minimal concentrations of retinoic acid induce stimulation by retinoic acid 8 and promote entry into meiosis in isolated pregonadal and gonadal mouse primordial germ cells.
abstract: In the present study, we demonstrate that minimal concentrations (≤ 1 nM) of retinoic acid (RA), equivalent to the quantity contaminating serum-containing culture medium, are sufficient to promote meiotic entry and progression through meiotic prophase I (MPI) stages in isolated 12.5-days postcoitum (dpc) XX and XY mouse primordial germ cells (PGCs) in culture. Similarly, we found that the same low RA concentration up-regulated or induced stimulation by retinoic acid 8 (Stra8) in such cells, both at mRNA and protein level. In preleptotene/leptotene germ cells, STRA8 was localized in nuclear dots that disappeared at later MPI stages. In addition to Stra8, other meiotic genes such as Dmc1 and Rec8 appeared stimulated by RA directly in PGCs with similar concentration-dependent trends. Finally, we found that RA induced Stra8, Sycp3, Dmc1, and Rec8 transcripts, promoting meiotic entry in culture also in pregonadal 10.5-dpc PGCs of both sexes. When cultured isolated from somatic cells, such PGCs, however, were unable to progress through MPI stages, while after entering meiosis, they progressed through MPI when cultured within aorta/gonad/mesonephros tissues. We conclude that besides RA, germ cell intrinsic factors and other exogenous signals from the surrounding somatic cells are probably necessary for meiotic entry and progression in mouse PGCs.
authors: Department of Biomedicine and Prevention, Section of Histology and Embryology, University of Rome Tor Vergata, Rome, Italy.
authors: Marianna
authors: M
authors: Tedesco
authors: Maria Giovanna
authors: MG
authors: Desimio
authors: Francesca Gioia
authors: FG
authors: Klinger
authors: Massimo
authors: M
authors: De Felici
authors: Donatella
authors: D
authors: Farini
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053595:Embryonic Stem Cells; D005854:Germ Cells / Q000187:drug effects* / Q000378:metabolism; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D028044:Phosphate-Binding Proteins; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C513032:Dmc1 protein, mouse; D009687:Nuclear Proteins; D028044:Phosphate-Binding Proteins; D010750:Phosphoproteins; D011506:Proteins; C465863:Rec8 protein, mouse; C102019:Stra8 protein, mouse; D014212:Tretinoin
keywords: STRA8; meiosis; primordial germ cells; retinoic acid