2. Academic Validation
  3. Glycogen metabolism in mouse embryonic Sertoli cells sustains the germ line through the lactate shuttle

Glycogen metabolism in mouse embryonic Sertoli cells sustains the germ line through the lactate shuttle

  • bioRxiv. 2025 Jul 27:2025.07.23.666216. doi: 10.1101/2025.07.23.666216.
Martín A Estermann 1 2,  Joseph Sheheen 3 2,  Sara A Grimm 4,  Boris Tezak 3 5,  Yu-Ying Chen 1,  Tsuyoshi Morita 6,  Humphrey H C Yao 1 2,  Blanche Capel 3 2 7
Affiliations

Affiliations

  • 1 Reproductive Developmental Biology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
  • 2 These authors contributed equally.
  • 3 Department of Cell Biology, Duke University Medical Center, Durham, NC 27701, USA.
  • 4 Integrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
  • 5 Biology Department, Wesleyan University, Middletown, CT 06459, USA.
  • 6 Oral and Maxillofacial Anatomy, Tokushima University Graduate School, Tokushima 770-8504, Japan.
  • 7 Lead contact.
PMID: 40777410 DOI: 10.1101/2025.07.23.666216
Abstract

Metabolites are key regulators of cell fate decisions, epigenetic remodeling, and lineage commitment. While genetic pathways governing testis differentiation are well studied, the role of metabolism remains poorly understood. In this study, we investigated a transient, male-specific accumulation of glycogen in supporting (Sertoli) cells of embryonic testis in mice. Although glycogen metabolism was dispensable for Sertoli cell differentiation, its disruption led to reduced lactate production and impaired PGCs ability to colonize the newly forming testis cords. Inhibiting lactate transport further revealed a critical metabolic coupling between Sertoli and germ cells during early testis development. Surprisingly, external lactate or glucose supplementation failed to rescue the germ cell phenotype. These findings suggest that glycogen accumulation supports a critical developmental window in which both Sertoli and germ cells are metabolically constrained and unable to rely on external carbon sources. This highlights a sensitive period during testicular development where nutrient scarcity could have long-term consequences for fertility.

Keywords

Fertility; Lactate Shuttle; Metabolic coupling; Metabolism; Sex Determination; Sperm.

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