Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier function

Abstract

Blood testis barrier (BTB) is one of the tightest blood-barriers controlling the entry of substances into the intratubular fluid. Diabetes Mellitus (DM) is an epidemic metabolic disease concurrent with falling fertility rates, which provokes severe detrimental BTB alterations. It induces testicular alterations, disrupting the metabolic cooperation between the cellular constituents of BTB, with dramatic consequences on sperm quality and fertility. As Sertoli cells are involved in the regulation of spermatogenesis, providing nutritional support for germ cells, any metabolic alteration in these cells derived from DM may be responsible for spermatogenesis disruption, playing a crucial role in fertility/subfertility associated with this pathology. These cells have a glucose sensing machinery that reacts to hormonal fluctuations and several mechanisms to counteract hyper/hypoglycemic events. The role of DM on Sertoli/BTB glucose metabolism dynamics and the metabolic molecular mechanisms through which DM and insulin deregulation alter its functioning, affecting male reproductive potential will be discussed.

Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception

“…Several subfertility/infertility-promoting diseases have been shown to deregulate glycolysis in these cells. Diabetes Mellitus (DM) is one of these diseases (for review [12,74]) and has a high prevalence in developed and in developing countries, particularly due to changes in eating behavior and the intake of food rich in fats. Euglycemia is virtually impossible to attain in diabetic individuals, although crucial advances have been made in search of treatment with insulin, insulin analogs and sensitizers, insulin secretagogues and other antidiabetic drugs.…”

“…The BTB regulates the exchange of substances between the rete testis fluid and the lymph or plasma [10], controlling the luminal fluid content where germ cells develop. Thus, it is understandable that BTB dynamics and functioning are deregulated in several diseases that end-up in male subfertility/infertility [11][12][13]. Moreover, it can also be a target for male contraception [14,15].…”

Protective Effect of Allium cepa (Onion) Seeds (AC) Extract on Histopathology of Testis in STZ-Induced Male Rats

“…About 90% of diabetic patients have disturbances in sexual function, epidemic metabolic disease, which provokes severe detrimental blood testis barrier (BTB) alterations leading to a decreased fertility rates (Alves et al, 2013). Infertile male diabetics tend to suffer from decreased sex libido, diminishing sperm count, endocrine disturbance, impaired penile erection and ejaculation (Zhao et al, 2010).…”

The Burden of Metabolic Diseases on Male Reproductive Health

“…They can also suffer coitus difficulties due to excessive pubic fat deposition, which leads to other reproductive health risks, such as scrotal heating, responsible for defects in spermatogenesis. T2DM patients are also prone to erectile dysfunction and scrotal heating due to vascular disease [8]. Nevertheless, the most severe and persistent effects of metabolic disorders on male reproductive function are linked to hormonal impairment.…”

“…LH stimulates testosterone release from Leydig Cells, so ultimately reproductive axis disruption leads to the formerly mentioned lower testosterone concentration. Sertoli cells are crucial for spermatogenesis because they establish the blood-testis barrier (BTB), one of the tightest blood-barriers of our body [8]. Testosterone (and their precursors) and FSH direct Sertoli cell metabolism towards a glycolytic profile, uptaking more glucose, increasing lactate dehydrogenase (LDH) efficiency and releasing more lactate and acetate into the seminiferous tubule's adluminal space [9,10].…”