title: Direct effects of retinoic acid on entry of fetal male germ cells into meiosis in mice.
abstract: In both male and female germ cells of mice, retinoic acid (RA) is a meiosis-inducing factor. In the present study, we used a germ cell culture system to examine the direct effects of RA on meiotic initiation in male germ cells at the stage when they normally enter mitotic arrest to determine the extent to which fetal male germ cells can respond to exogenous RA to alter their sex-specific pathway. Male germ cells between 13.5 and 15.5 days postcoitum (dpc) were isolated from Pou5fl-green fluorescent protein transgenic fetuses and cultured with or without RA for up to 6 days. In the absence of RA, male germ cells did not undergo DNA replication and did not enter meiosis in culture. However, in the presence of RA, male germ cells isolated at 13.5 dpc expressed Stra8 and initiated the meiotic process. The ratio of cells entering meiosis gradually decreased as cells were isolated progressively at later stages. By 15.5 dpc, isolated male germ cells lost their ability to respond to RA signaling. These cells remained dispersed as single cells and progressed along the male differentiation pathway, as evidenced by the establishment of male-specific methylation imprints regardless of the presence or absence of RA. We conclude that male germ cells maintain sexual bipotency until 14.5 dpc that can be reversed by the addition of RA. Once male germ cells enter mitotic arrest, however, they appear to be committed irreversibly to the male-specific differentiation pathway even in the presence of exogenously added RA.
authors.affiliation: Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii 96813, USA.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ohta
authors.forename: Yanling
authors.initials: Y
authors.lastname: Lin
authors.forename: Nathanael
authors.initials: N
authors.lastname: Hogg
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamazaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004261:DNA Replication; D004268:DNA-Binding Proteins; D047109:Fetal Development; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018392:Genomic Imprinting; D008297:Male; D008540:Meiosis; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D019849:Sex Determination Processes; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism; D014212:Tretinoin / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C094335:H19 long non-coding RNA; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011506:Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; C490060:SYCP3 protein, human; C102019:Stra8 protein, mouse; D014212:Tretinoin; C498796:Dnmt3l protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases
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