High glucose levels affect spermatogenesis: an in vitro approach

Abstract

Besides known factors that may cause male infertility, systemic diseases such as diabetes mellitus may further exacerbate a decline in male fertility. This metabolic disease, clinically characterised by a hyperglycaemic phenotype, has devastating consequences in terms of human health, with reproductive dysfunction being one of the associated clinical complications. Nonetheless, the mechanisms responsible for such alterations are still poorly understood due to the multiplicity of factors involved in the induced pathophysiological changes. With this in mind, we focused on the main mediator of diabetes-associated alterations and performed an in vitro approach to address the effects of high glucose conditions on spermatogenesis, avoiding other confounding in vivo factors. Mouse (5 days post partum) testis fragments were cultured on agar gel stands at a gas-liquid interface with either 5, 25 or 50mM D-glucose for 3 weeks. Stereological analysis revealed that high D-glucose levels increased Sertoli cell number (P<0.05) and decreased tubular luminal area (P<0.01), suggesting an impairment of this somatic cell type. Moreover, higher proliferative activity in a TM4 Sertoli cell line exposed to high D-glucose was found (P<0.05) without compromising cell viability (P>0.05), further suggesting altered Sertoli cell maturation. Overall, high D-glucose concentrations may lead to impairment of Sertoli cell function, which, given their significant role in spermatogenic control, may compromise male fertility.

Role of Antioxidant Natural Products in Management of Infertility: A Review of Their Medicinal Potential

“…Furthermore, molecular mechanisms of glucose fluctuation due to DM were discovered to cause detrimental effects on testicular function [ 148 ]. High D-glucose concentrations led to alterations in Sertoli cells which are responsible for the production of lactate, a primary source for the maturation of spermatocytes and spermatids [ 149 , 150 ]. However the deprivation of insulin and insufficient glucose consumption were followed by lower lactate production as well as modulations in several glucose transporters [ 151 , 152 , 153 ].…”

Elevated CCL2 causes Leydig cell malfunction in metabolic syndrome

“…Infertility affects 10% of couples worldwide, and male factors contribute to more than 40% of the infertility cases (1,2). Metabolic syndrome (MetS) is a cluster of abnormalities including type 2 diabetes, obesity, dyslipidemia, and hypertension that has been proposed as a potential cause of male infertility (3)(4)(5)(6). MetS has been associated with a higher incidence of male infertility compared with healthy men, as indicated by decreased serum testosterone/estrogen ratio and poor semen quality.…”

Orexin A-Mediated Modulation of Reproductive Activities in Testis of Normal and Cryptorchid Dogs: Possible Model for Studying Relationships Between Energy Metabolism and Reproductive Control

“…An important prerequisite for the success of spermatogenesis is that Sertoli and germ cells cooperate for metabolic pathway activation to ensure adequate lactate concentrations inside testis tubule lumen (1), as confirmed by studying the etio-pathogenesis of different diseases. For example, diabetes characterized by a hyperglycemic condition is associated with male infertility (2). Numerous additional studies have demonstrated direct interactions between spermatogenesis anomalies, infertility disorders, and high estradiol (E) levels.…”