Metabolic Control of Germline Formation and Differentiation in Mammals

Yohei Hayashi; Yasuhisa Matsui

doi:10.1159/000520662

Metabolic Control of Germline Formation and Differentiation in Mammals

Sex Dev. 2022;16(5-6):388-403. doi: 10.1159/000520662. Epub 2022 Jan 27.

Authors

Yohei Hayashi^{1

2

3}, Yasuhisa Matsui^{1

2

3}

Affiliations

¹ Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan.
² Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
³ Graduate School of Medicine, Tohoku University, Sendai, Japan.

Abstract

Background: The germ cell lineage involves dynamic epigenetic changes during its formation and differentiation that are completely different from those of the somatic cell lineage. Metabolites and metabolic pathways have been reported as key factors related to the regulation of epigenetics as cofactors and substrates. However, our knowledge about the metabolic characteristics of germ cells, especially during the fetal stage, and their transition during differentiation is quite limited due to the rarity of the cells. Nevertheless, recent developments in omics technologies have made it possible to extract comprehensive metabolomic features of germ cells.

Summary: In this review, we present the latest researches on the metabolic properties of germ cells in 4 stages: primordial germ cell specification, fetal germ cell differentiation, spermatogenesis, and oogenesis. At every stage, extensive published data has been accumulated on energy metabolism, and it is possible to describe its changes during germ cell differentiation in detail. As pluripotent stem cells differentiate into germ cells, energy metabolism shifts from glycolysis to oxidative phosphorylation; however, in spermatogenesis, glycolytic pathways are also temporarily dominant in spermatogonial stem cells. Although the significance of metabolic pathways other than energy metabolism in germ cell differentiation is largely unknown, the relation of the pentose phosphate pathway and Ser-Gly-one-carbon metabolism with germ cell properties has been suggested at various stages. We further discuss the relationship between these characteristic metabolic pathways and epigenetic regulation during germ cell specification and differentiation. Finally, the relevance of dietary and supplemental interventions on germ cell function and epigenomic regulation is also discussed.

Key messages: Comprehensive elucidation of metabolic features and metabolism-epigenome crosstalk in germ cells is important to reveal how the characteristic metabolic pathways are involved in the germ cell regulation. The accumulation of such insights would lead to suggestions for optimal diets and supplements to maintain reproductive health through modulating metabolic and epigenetic status of germ cells.

Keywords: Development; Differentiation; Epigenome; Germ cells; Metabolism.

Publication types

Review

Grants and funding

For part of this work, Y.H. was supported by Grant-in-Aid for Scientific Research (KAKENHI) (C) (grant 19K06434), KAKENHI in the Innovative Areas, “Sex Spectrum” (grant 20H04917) and “Ensuring integrity in gametogenesis” (grant 19H05238) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), Takeda Science Foundation, Kato Memorial Bioscience Foundation, the Inamori Foundation, and Astellas Foundation for Research on Metabolic Disorders. Y.M. was supported by KAKENHI (B) (grant 19H03231) from MEXT and The Uehara Memorial Foundation.