Sertoli Cell Metabolism in Male Reproductive Health

Sertoli cells form the metabolic hub of the seminiferous epithelium, supplying developing germ cells with essential fuels, growth factors and redox balance. They take up glucose and convert it predominantly into lactate via glycolysis, exporting this energetic substrate to spermatocytes and spermatids. Beyond glucose, Sertoli cells exhibit metabolic plasticity, oxidising amino acids such as glutamine and engaging in glycogen turnover to buffer energy supply under fluctuating conditions. Lipid handling within these cells governs membrane remodelling and steroid responsiveness, while reactive oxygen species generated during metabolism act as signalling mediators for proliferation and tight‐junction dynamics. Dysregulation of these pathways underlies a spectrum of fertility impairments, from diet‐induced oxidative stress to toxin‐driven mitochondrial dysfunction. The interplay between metabolic enzymes, transporters and intracellular signalling cascades ensures that spermatogenesis proceeds with high fidelity, making Sertoli cell metabolism a central determinant of male reproductive health and a promising target for therapeutic intervention.

Research from Nature Portfolio

Studies in transgenic rodent models overexpressing the calcium‐binding protein regucalcin have revealed that Sertoli cells can shift from simple glucose metabolism toward enhanced glutamine utilisation, still yielding increased lactate for germ cell support while conserving glucose. This work underscored the role of regucalcin in modulating alanine transaminase expression and glutamine flux, highlighting metabolic adaptability as a countermeasure in subfertile contexts. Complementary investigations into the Ndrg3 gene demonstrated that lactate produced by Sertoli cells activates ERK1/2 signalling in primary spermatocytes, facilitating double‐strand break repair during meiosis. Loss of Ndrg3 impaired ERK activation and delayed homologous recombination, linking Sertoli‐derived metabolites directly to genome integrity and fertility outcomes.

Sertoli Cell Metabolism in Male Reproductive Health publication trend

The graph below shows the total number of articles in sertoli cell metabolism in male reproductive health across all publications each year (not limited to Nature Index journals).

Technical terms

Glycolysis: The enzymatic breakdown of glucose to pyruvate, generating ATP and precursors for biosynthesis.

Lactate dehydrogenase A (LDHA): A key enzyme that catalyses the conversion of pyruvate to lactate, pivotal for Sertoli cell support of germ cells.

β-oxidation: The mitochondrial process by which fatty acids are degraded to acetyl-CoA, supplying energy and biosynthetic substrates.

Regucalcin (RGN): A calcium-binding protein that regulates intracellular signalling and metabolic enzyme expression in Sertoli cells.

ERK1/2 pathway: A mitogen-activated protein kinase cascade involved in cell proliferation, differentiation and stress responses.

MicroRNA (miR-1285-3p): A small non-coding RNA that post-transcriptionally regulates gene expression, here targeting glycolytic enzymes in Sertoli cells.

References

1. Glucose and glutamine handling in the Sertoli cells of transgenic rats overexpressing regucalcin: plasticity towards lactate production. Scientific Reports (2018).
2. Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells. Scientific Reports (2017).
3. Ldha-Dependent Metabolic Programs in Sertoli Cells Regulate Spermiogenesis in Mouse Testis. Biology (2022).
4. Atlas of metabolism reveals palmitic acid results in mitochondrial dysfunction and cell apoptosis by inhibiting fatty acid β-oxidation in Sertoli cells. Frontiers in Endocrinology (2022).
5. miR-1285-3p targets TPI1 to regulate the glycolysis metabolism signaling pathway of Tibetan sheep Sertoli cells. PLOS ONE (2022).
6. Testicular Glycogen Metabolism: An Overlooked Source of Energy for Spermatogenesis?. BioChem (2022).
7. A Brazilian pulp and paper mill effluent disrupts energy metabolism in immature rat testis and alters Sertoli cell secretion and mitochondrial activity. Animal Reproduction (2020).