1. Proteomic and metabolomic analyses uncover sex-specific regulatory pathways in mouse fetal germline differentiation†
- Author
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Akio Kanai, Tomoyoshi Soga, Masaru Mori, Asuka Takehara, Yumi Ito-Matsuoka, Kaori Igarashi, Keiko Tanaka, Nobuo Yaegashi, Yasuhisa Matsui, and Yohei Hayashi
- Subjects
0301 basic medicine ,Male ,Proteomics ,Sex Differentiation ,Cell division ,Mice, Transgenic ,Biology ,Embryonic Germ Cells ,Germline ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Sex Factors ,medicine ,Animals ,Metabolomics ,Epigenetics ,Transcription factor ,Gene Expression Regulation, Developmental ,Cell Differentiation ,Cell Biology ,General Medicine ,DNA ,DNA Methylation ,Oocyte ,Embryo, Mammalian ,Embryonic stem cell ,Cell biology ,030104 developmental biology ,Proteostasis ,medicine.anatomical_structure ,Reproductive Medicine ,Female ,030217 neurology & neurosurgery ,Germ cell ,Genome-Wide Association Study ,Transcription Factors - Abstract
Regulatory mechanisms of germline differentiation have generally been explained via the function of signaling pathways, transcription factors, and epigenetic regulation; however, little is known regarding proteomic and metabolomic regulation and their contribution to germ cell development. Here, we conducted integrated proteomic and metabolomic analyses of fetal germ cells in mice on embryonic day (E)13.5 and E18.5 and demonstrate sex- and developmental stage-dependent changes in these processes. In male germ cells, RNA processing, translation, oxidative phosphorylation, and nucleotide synthesis are dominant in E13.5 and then decline until E18.5, which corresponds to the prolonged cell division and more enhanced hyper-transcription/translation in male primordial germ cells and their subsequent repression. Tricarboxylic acid cycle and one-carbon pathway are consistently upregulated in fetal male germ cells, suggesting their involvement in epigenetic changes preceding in males. Increased protein stability and oxidative phosphorylation during female germ cell differentiation suggests an upregulation of aerobic energy metabolism, which likely contributes to the proteostasis required for oocyte maturation in subsequent stages. The features elucidated in this study shed light on the unrevealed mechanisms of germ cell development.
- Published
- 2020