2. Academic Validation
  3. Glycogen and lactate metabolism in mouse fetal Sertoli cells sustain the germ line

Glycogen and lactate metabolism in mouse fetal Sertoli cells sustain the germ line

  • Cell Rep. 2026 Mar 24;45(3):117069. doi: 10.1016/j.celrep.2026.117069.
Martín A Estermann 1,  Joseph Sheheen 2,  Sara A Grimm 3,  Boris Tezak 4,  Yu-Ying Chen 5,  Tsuyoshi Morita 6,  Humphrey H-C Yao 5,  Blanche Capel 7
Affiliations

Affiliations

  • 1 Reproductive Developmental Biology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Electronic address: [email protected].
  • 2 Department of Cell Biology, Duke University Medical Center, Durham, NC 27701, USA.
  • 3 Integrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
  • 4 Department of Cell Biology, Duke University Medical Center, Durham, NC 27701, USA; Biology Department, Wesleyan University, Middletown, CT 06459, USA.
  • 5 Reproductive Developmental Biology Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
  • 6 Oral and Maxillofacial Anatomy, Tokushima University Graduate School, Tokushima 770-8504, Japan.
  • 7 Department of Cell Biology, Duke University Medical Center, Durham, NC 27701, USA. Electronic address: [email protected].
PMID: 41811847 DOI: 10.1016/j.celrep.2026.117069
Abstract

Metabolites are key regulators of cell fate decisions, chromatin remodeling, and lineage commitment. While genetic pathways governing testis differentiation are well studied, the role of metabolism remains poorly understood. In this study, we investigate the transient, male-specific accumulation of glycogen in supporting cells of the fetal testis in mice, between embryonic days 11.5 and 13.5. Blocking glycogen metabolism/accumulation in vivo and in vitro is dispensable for Sertoli cell differentiation. However, its disruption leads to reduced lactate production and reduced germ cell number in the testis. Inhibiting lactate transport reveals a critical metabolic coupling between Sertoli and germ cells during early testis development. Surprisingly, external lactate or glucose supplementation fails 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.

Keywords

CP: developmental biology; CP: metabolism; fertility; lactate shuttle; metabolic coupling; metabolism; metabolofertility; sex determination; sperm.

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