Glucose and glutamine handling in the Sertoli cells of transgenic rats overexpressing regucalcin: plasticity towards lactate production

Abstract

Sertoli cells (SCs) possess the unparalleled ability to provide the germ line with growth factors and nutrients. Although SCs can oxidize amino acids, e.g., glutamine, they mostly metabolize glucose, producing high amounts of lactate, the germ cells preferential substrate. Regucalcin (RGN) is a calcium-binding protein that has been indicated as a regulator of cell metabolism. In this study, we investigated glucose and glutamine handling in the SCs of transgenic rats overexpressing RGN (Tg-RGN) comparatively with wild-type (Wt) littermates. Primary SCs isolated from adult Tg-RGN animals and maintained in culture for 24 hours, produced and exported more lactate, despite consuming less glucose. These observations were underpinned by increased expression of alanine transaminase, and augmented glutamine consumption, suggesting that alternative routes are contributing to the enhanced lactate production in the SCs of Tg-RGN rats. Moreover, lactate seems to be used by germ cells, with diminished apoptosis being detected in the seminiferous tubules of Tg-RGN animals cultured ex vivo. The obtained results showed a distinct metabolism in the SCs of Wt and Tg-RGN rats widening the roles assigned to RGN in spermatogenesis. These findings also highlighted the plasticity of SCs metabolism, a feature that would be exploited in the context of male infertility.

Mitochondria Content and Activity Are Crucial Parameters for Bull Sperm Quality Evaluation

“…All these processes are embedded within the specific testicular microenvironment, including the Sertoli and the Leydig cells. The first guard the blood–testis barrier, control the number of germ cells via apoptosis, and are a major energy source for spermatogenesis (secrete lactate and produce ATP through lipid β-oxidation) [ 82 , 83 ]. The latter produce steroid hormones and cAMP, which accelerates cholesterol transport to the IMM and stimulates the production of ATP in the mitochondria [ 84 ].…”

Are there differences in the biochemical profile of bilateral normal testes? A 3.0 T 1H‐MR spectroscopy study

“…The exact role of Glu in human testis is still under investigation. Amino acids, including Glu besides serving as nutrients in energy metabolism, they represent a significant signalling molecule in the regulation of complex physiological processes during spermatogenesis (Hu et al, 2004; Mateus et al, 2018; Plaitakis, Kalef‐Ezra, Kotzamani, Zaganas, & Spanaki, 2017; Storto et al, 2001; Tang et al, 2019).…”

Proton MR Spectroscopy in Assessing the Biochemical Milieu of Human Testes

“…An autopsy study of bilateral normal testes showed a lower daily sperm production per testis by ~13% in the left side, positively correlated with both total testicular weight and weight of testicular parenchyma, which were about 10% lower in the left testis when compared to the right side 63 . An increase in Lac and Glu could probably be attributed to impairment of spermatogenesis in normal left testis, resulting in an increase in the demands for these metabolites by the left side 21,41–49 . Besides defective spermatogenesis, a possible increase in levels of OS in normal left testis might also contribute to the increase in Glu levels, a metabolite with known antioxidant effects in human testes 45 …”

“…4). 21,[41][42][43][44][45][46][47][48][49] Both Lac and amino acids represent important nutrients in energy metabolism during spermatogenesis. An autopsy study of bilateral normal testes showed a lower daily sperm production per testis by ~13% in the left side, positively correlated with both total testicular weight and weight of testicular parenchyma, which were about 10% lower in the left testis when compared to the right side.…”

“…63 An increase in Lac and Glu could probably be attributed to impairment of spermatogenesis in normal left testis, resulting in an increase in the demands for these metabolites by the left side. 21,[41][42][43][44][45][46][47][48][49] Besides defective spermatogenesis, a possible increase in levels of OS in normal left testis might also contribute to the increase in Glu levels, a metabolite with known antioxidant effects in human testes. 45…”