Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to determine whether sperm quality, fertilization capacity, and subsequent embryo development are altered in diabetic male mice and whether differences in facilitative glucose transporter (GLUT; now known as solute carrier family 2, SLC2A) expression in the testis and sperm exist. Using two type 1 diabetic mouse models, SLC2A expression in the testis and sperm was determined by western immunoblotting and immunofluorescence staining. To address sperm quality and fertilization capacity, computer-assisted sperm analysis and in vitro fertilization were performed. SLC2A1, SLC2A3, and SLC2A5 did not change in expression in the testes or sperm between diabetic and non-diabetic mice. SLC2A8 and SLC2A9b were less expressed in the testes of both diabetic models versus controls. SLC2A9a was not expressed in the Akita testis or sperm when compared with strain-matched controls. 3beta-hydroxysteroid dehydrogenase (HSD3B) expression was significantly decreased in the Leydig cells from the diabetic mice. Sperm concentration and motility were significantly lower in both the diabetics when compared with the control. These parameters normalized in Akita diabetic males treated with insulin. In addition, fertilization rates were significantly lower in the Akita group (17.9%) and the streptozotocin (STZ)-injected male group (43.6%) when compared with the normal group (88.8%). Interestingly, of the fertilized zygotes, embryo developmental rates to the blastocyst stage were lower in both diabetic models (7.1% Akita and 50.0% STZ) when compared with controls (71.7%). Male diabetes may cause male subfertility by altering steroidogenesis, sperm motility, and SLC2A expression. This is the first study to link a paternal metabolic abnormality to a sperm effect on cell division and subsequent embryonic development.
 ...
PMID:Paternal effect on embryo quality in diabetic mice is related to poor sperm quality and associated with decreased glucose transporter expression. 1855 60

Male patients with diabetes type I and type II present more frequently with subfertility. On a subcellular level, increased apoptosis signalling and the rate of DNA fragmentation have an impact on sperm fertilizing capacity. The aim of this study was to evaluate apoptosis signalling and the role of DNA fragmentation in sperm of patients with diabetes type I and type II to gain further insight into the pathophysiology of diabetes-related subfertility in men. Semen specimens collected from 18 healthy fertile donors and 27 donors with diabetes type I (n=13) or type II (n=14) were prepared via density gradient centrifugation. High- and low-density sperm subpopulations were assessed for apoptosis markers (disrupted transmembrane mitochondrial potential, activated caspase 3) and reactive oxygen species, as well as DNA fragmentation, by flow cytometry. The results show that ejaculates of diabetic men contain significantly (P<0.05) higher concentrations of spermatozoa with disrupted transmembrane mitochondrial potential, activated caspase 3, reactive oxygen species and fragmented DNA when compared with healthy fertile donors. The effect is more pronounced in men with diabetes type II. All measured parameters were inversely correlated with the sperm fertilizing potential, indicating a possible mechanism of subfertility in diabetic men. Diabetes mellitus can affect male fertility. Earlier studies have proved reduced sperm motility and lower DNA integrity in germ cells of diabetic patients. It was postulated that higher levels of oxidative stress may contribute to this findings. However, until now the pathophysiology of diabetes-related male subfertility is not fully understood. Our study showed for the first time that apoptosis signalling, measured by disrupted transmembrane mitochondrial potential and activated caspase 3, is significantly increased in sperm from males with diabetes type-I and type-II. Particularly, a disrupted transmembrane mitochondrial potential contributes to the reduced sperm motility. Together with the increased presence of intracellular reactive oxygen species and higher levels of sperm DNA fragmentation, several subcellular factors are now available to explain subfertility in diabetic males.
 ...
PMID:Sperm apoptosis signalling in diabetic men. 2279 31

The incidence of type 2 diabetes mellitus and its prodromal stage, pre-diabetes, is rapidly increasing among young men, leading to disturbances in testosterone synthesis. However, the impact of testosterone deficiency induced by these progressive stages of diabetes on the metabolic behavior of Sertoli cells remains unknown. We evaluated the effects of testosterone deficiency associated with pre-diabetes and type 2 diabetes on Sertoli cells metabolism, by measuring (1) the expression and/or activities of glycolysis and glycogen metabolism-related proteins and (2) the metabolite secretion/consumption in Sertoli cells obtained from rat models of different development stages of the disease, to unveil the mechanisms by which testosterone deregulation may affect spermatogenesis. Glucose and pyruvate uptake were decreased in cells exposed to the testosterone concentration found in pre-diabetic rats (600nM), whereas the decreased testosterone concentrations found in type 2 diabetic rats (7nM) reversed this profile. Lactate production was not altered, although the expression and/or activity of lactate dehydrogenase and monocarboxylate transporter 4 were affected by progressive testosterone-deficiency. Sertoli cells exposed to type 2 diabetic conditions exhibited intracellular glycogen accumulation. These results illustrate that gradually reduced levels of testosterone, induced by progressive stages of diabetes mellitus, favor a metabolic reprogramming toward glycogen synthesis. Our data highlights a pivotal role for testosterone in the regulation of spermatogenesis metabolic support by Sertoli cells, particularly in individuals suffering from metabolic diseases. Such alterations may be in the basis of male subfertility/infertility associated with the progression of diabetes mellitus.
...
PMID:Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells. 2614 70

Obesity, defined as excessive accumulation of fat in adipose tissue, is a metabolic disorder resulting from behavioral, environmental and heritable causes. Obesity increases the risks of hypertension, diabetes, cardiovascular disease, sleep apnea, respiratory problems, osteoarthritis and cancer. Meanwhile, the negative impact of obesity on male reproduction is gradually recognized. According to the clinical investigations and animal experiments, obesity is correlated with reductions in sperm concentration and motility, increase in sperm DNA damage and changes in reproductive hormones. Several mechanisms can elucidate the effects of obesity on sperm functions and male subfertility, i.e., the excessive conversion of androgens into estrogens in redundant adipose tissue causes sexual hormone imbalance, subsequently resulting in hypogonadism. Secondly, adipokines produced by adipose tissue induce severe inflammation and oxidative stress in male reproductive tract, directly impairing testicular and epididymal tissues. Moreover, increased scrotal adiposity leads to increase gonadal heat, continuously hurting spermatogenesis. Therefore, obesity alters the systematic and regional environment crucial for spermatogenesis in testis and sperm maturation in epididymis, and finally results in poor sperm quality including decreased sperm motility, abnormal sperm morphology and acrosome reaction, changed membrane lipids and increased DNA damage. Furthermore, recent studies indicate that epigenetic changes may be a consequence of increased adiposity. A major effort to identify epigenetic determinants of obesity revealed that sperm DNA methylation and non-coding RNA modification are associated with BMI changes and proposed to inherit metabolic comorbidities across generations. This review will explain how obesity-related changes in males to influence sperm function and male fertility as well.
 ...
PMID:Obesity, a serious etiologic factor for male subfertility in modern society. 2874 41