madman
Super Moderator
Abstract
The metabolic disorders caused by diabetes can lead to various complications, including dysfunction of the male reproductive system. In patients with diabetes, long-term hyperglycemia results in diabetic vascular neuropathy, oxidative stress injury, abnormal zinc metabolism, and insulin resistance syndrome. In addition, insulin deficiency and resistance in diabetes can damage the hypothalamus, pituitary gland, gonads, and perigonads. This can reduce the secretion of sex hormones including gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, and testosterone, and can lead to testicular atrophy, stromal cell atrophy, seminiferous tubule damage, spermatogenic cell damage, and other structural injuries of the male reproductive organs. These actions can affect male fertility and reproductive health. Herein, we review studies that report a causative role of diabetes in male reproductive function. We also discuss the evidence-based mechanisms involved in the processes of diabetes-related male sexual and reproductive dysfunction as well as the progress in treatment.
Diabetes mellitus (DM) is a metabolic disease that seriously endangers human health. The incidence rate of DM is very high, and the age of onset has been decreasing worldwide. The latest data from the International Diabetes Federation (IDF) show the number of adults with diabetes is up to 463 million worldwide and is estimated to increase to 578 million by 2030.
DM is due to the absolute or relative deficiency of insulin (INS) and insulin resistance (IR), which lead to a decrease in the INS utilization rate and metabolic disorder. In patients with DM, long-term hyperglycemia can cause diabetic vascular neuropathy. Diabetes induced metabolic disorder also leads to oxidative stress, abnormal zinc metabolism, and IR syndrome, all of which affect male fertility and reproductive health. It has been shown that decreased semen quality and impaired reproductive function occur to nearly half of the male patients with diabetes. DM incidence is higher in China compared to other countries. The number of male patients with diabetes is gradually increasing, and so are the fertility problems of the male population. Therefore, male reproduction is attracting more and more attention. In this article, we provide an overview and a review of the reproductive pathology of DM males, and evidence on the mechanisms involved in the processes, leading us to conclude that further investigation would benefit our understanding of DM-induced male reproductive dysfunction and would aid in the development of novel ways to improve male reproductive health.
*Diabetes Mellitus Affects Male Reproduction
DM affects male reproduction in four conditions, including erectile dysfunction, ejaculation, structural changes in reproductive organs, and changes in the semen quality.
*Effect of Oxidative Stress on Male Reproduction in Diabetes Mellitus
*Effect of Abnormal Zinc Metabolism in Males With Diabetes Mellitus
*Role of Hypothalamic Pituitary Gonadal Axis in the Reproduction of Diabetic Men
*Effect of Insulin Resistance on Male Reproduction
*Progression in the Treatment of Diabetes Mellitus-Related Male Reproductive Dysfunction
Conclusion and Future Directions
DM is a hormonal and metabolic disorder that causes many complications and affects multiple organs and systems in the human body including the male reproductive system. Although the molecular basis of diabetes-caused male sexual and reproductive dysfunction is as yet not completely known, abundant evidence shows that multiple factors and mechanisms are involved in the process (Figure 1). Oxidative stress is a common mechanism underlying diabetic complications. Microcirculation disturbance and oxidative stress are considered to be the main factors causing reproductive system damage. Hyperglycemia leads to the impairment of vascular endothelial function, including the decrease in endothelial NO (eNO) synthesis, the increase of oxidative stress, and the glycosylation of elastic fibers in the vascular wall. Finally, hyperglycemia causes peripheral neurovascular diseases, leading to DMED and bladder dysfunction. Semen quality is characterized by decreased sperm concentration and motility, as well as a high incidence of sperm DNA damage, DNA breakage, and sperm apoptosis. DM causes HPGA damage, reduces hypothalamic GnRH secretion, and decreases plasma LH, FSH, PRL and T, resulting in spermatogenesis disorders. Impaired glucose utilization due to insulin deficiency leads to decreased pituitary protein synthesis and reduced gonadotropin secretion. Zinc has a strong antioxidant effect and plays a key role in scavenging free radicals. Zinc can inhibit lipid oxidation of sperm membrane and maintain the integrity of cell membrane structure. Oxidative stress affects zinc homeostasis and influences the expression of zinc transporters. IR is an important pathogenic factor and a pathological characteristic of T2DM. IR leads to erectile dysfunction and hypogonadism. Androgen ameliorates IR by increasing glucose transport, improving mitochondrial function, inhibiting inflammatory response, and suppressing the proliferation of adipocytes and adipoprogenitor cells, all of which slow down the development of DM.
Accumulating evidence shows that oxidative stress plays a very important role in the occurrence and development of DM, and therefore it is of great significance for the prevention and treatment of diabetes-related male reproductive dysfunction. There are still many key scientific issues regarding the mechanism regulating oxidative stress, including how cells perceive oxidative stress, the ROS threshold for activating key antioxidant molecules, and the effects of other forms of stress (such as metabolic stress, hypoxia, and inflammation) on the oxidative stress response. The molecular mechanism of inhibition of INS secretion by oxidative stress provides multiple candidate targets for the treatment of DM. Key factors (such as p38 mitogen-activated protein kinases and c-Jun N-terminal kinase 1) in the process of INS tolerance induced by oxidative stress can reverse oxidative stress-induced INS tolerance, suggesting that these factors can be potential targets for the treatment of DM. The unfolded protein response (UPR) is a cellular stress response related to endoplasmic reticulum stress. It has been found that UPR regulates the pathogenesis of IR and DM by affecting inflammation and lipid metabolism in the hypothalamus and is closely related to the maintenance of islet β-cell function. It provides a theoretical basis for the prevention and treatment of DM by targeting IRE1, a key factor in the pathogenesis of DM. Therefore, future research should screen and identify more potential drug targets based on further understanding of DM. In summary, as more and more mechanisms of action of oxidative stress in DM are unveiled, our understanding of the impact of DM on male reproduction will increase, and new and better approaches to improve reproductive health in men and to treat DM-caused male sexual and reproductive dysfunction will be developed.
The metabolic disorders caused by diabetes can lead to various complications, including dysfunction of the male reproductive system. In patients with diabetes, long-term hyperglycemia results in diabetic vascular neuropathy, oxidative stress injury, abnormal zinc metabolism, and insulin resistance syndrome. In addition, insulin deficiency and resistance in diabetes can damage the hypothalamus, pituitary gland, gonads, and perigonads. This can reduce the secretion of sex hormones including gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, and testosterone, and can lead to testicular atrophy, stromal cell atrophy, seminiferous tubule damage, spermatogenic cell damage, and other structural injuries of the male reproductive organs. These actions can affect male fertility and reproductive health. Herein, we review studies that report a causative role of diabetes in male reproductive function. We also discuss the evidence-based mechanisms involved in the processes of diabetes-related male sexual and reproductive dysfunction as well as the progress in treatment.
Diabetes mellitus (DM) is a metabolic disease that seriously endangers human health. The incidence rate of DM is very high, and the age of onset has been decreasing worldwide. The latest data from the International Diabetes Federation (IDF) show the number of adults with diabetes is up to 463 million worldwide and is estimated to increase to 578 million by 2030.
DM is due to the absolute or relative deficiency of insulin (INS) and insulin resistance (IR), which lead to a decrease in the INS utilization rate and metabolic disorder. In patients with DM, long-term hyperglycemia can cause diabetic vascular neuropathy. Diabetes induced metabolic disorder also leads to oxidative stress, abnormal zinc metabolism, and IR syndrome, all of which affect male fertility and reproductive health. It has been shown that decreased semen quality and impaired reproductive function occur to nearly half of the male patients with diabetes. DM incidence is higher in China compared to other countries. The number of male patients with diabetes is gradually increasing, and so are the fertility problems of the male population. Therefore, male reproduction is attracting more and more attention. In this article, we provide an overview and a review of the reproductive pathology of DM males, and evidence on the mechanisms involved in the processes, leading us to conclude that further investigation would benefit our understanding of DM-induced male reproductive dysfunction and would aid in the development of novel ways to improve male reproductive health.
*Diabetes Mellitus Affects Male Reproduction
DM affects male reproduction in four conditions, including erectile dysfunction, ejaculation, structural changes in reproductive organs, and changes in the semen quality.
*Effect of Oxidative Stress on Male Reproduction in Diabetes Mellitus
*Effect of Abnormal Zinc Metabolism in Males With Diabetes Mellitus
*Role of Hypothalamic Pituitary Gonadal Axis in the Reproduction of Diabetic Men
*Effect of Insulin Resistance on Male Reproduction
*Progression in the Treatment of Diabetes Mellitus-Related Male Reproductive Dysfunction
Conclusion and Future Directions
DM is a hormonal and metabolic disorder that causes many complications and affects multiple organs and systems in the human body including the male reproductive system. Although the molecular basis of diabetes-caused male sexual and reproductive dysfunction is as yet not completely known, abundant evidence shows that multiple factors and mechanisms are involved in the process (Figure 1). Oxidative stress is a common mechanism underlying diabetic complications. Microcirculation disturbance and oxidative stress are considered to be the main factors causing reproductive system damage. Hyperglycemia leads to the impairment of vascular endothelial function, including the decrease in endothelial NO (eNO) synthesis, the increase of oxidative stress, and the glycosylation of elastic fibers in the vascular wall. Finally, hyperglycemia causes peripheral neurovascular diseases, leading to DMED and bladder dysfunction. Semen quality is characterized by decreased sperm concentration and motility, as well as a high incidence of sperm DNA damage, DNA breakage, and sperm apoptosis. DM causes HPGA damage, reduces hypothalamic GnRH secretion, and decreases plasma LH, FSH, PRL and T, resulting in spermatogenesis disorders. Impaired glucose utilization due to insulin deficiency leads to decreased pituitary protein synthesis and reduced gonadotropin secretion. Zinc has a strong antioxidant effect and plays a key role in scavenging free radicals. Zinc can inhibit lipid oxidation of sperm membrane and maintain the integrity of cell membrane structure. Oxidative stress affects zinc homeostasis and influences the expression of zinc transporters. IR is an important pathogenic factor and a pathological characteristic of T2DM. IR leads to erectile dysfunction and hypogonadism. Androgen ameliorates IR by increasing glucose transport, improving mitochondrial function, inhibiting inflammatory response, and suppressing the proliferation of adipocytes and adipoprogenitor cells, all of which slow down the development of DM.
Accumulating evidence shows that oxidative stress plays a very important role in the occurrence and development of DM, and therefore it is of great significance for the prevention and treatment of diabetes-related male reproductive dysfunction. There are still many key scientific issues regarding the mechanism regulating oxidative stress, including how cells perceive oxidative stress, the ROS threshold for activating key antioxidant molecules, and the effects of other forms of stress (such as metabolic stress, hypoxia, and inflammation) on the oxidative stress response. The molecular mechanism of inhibition of INS secretion by oxidative stress provides multiple candidate targets for the treatment of DM. Key factors (such as p38 mitogen-activated protein kinases and c-Jun N-terminal kinase 1) in the process of INS tolerance induced by oxidative stress can reverse oxidative stress-induced INS tolerance, suggesting that these factors can be potential targets for the treatment of DM. The unfolded protein response (UPR) is a cellular stress response related to endoplasmic reticulum stress. It has been found that UPR regulates the pathogenesis of IR and DM by affecting inflammation and lipid metabolism in the hypothalamus and is closely related to the maintenance of islet β-cell function. It provides a theoretical basis for the prevention and treatment of DM by targeting IRE1, a key factor in the pathogenesis of DM. Therefore, future research should screen and identify more potential drug targets based on further understanding of DM. In summary, as more and more mechanisms of action of oxidative stress in DM are unveiled, our understanding of the impact of DM on male reproduction will increase, and new and better approaches to improve reproductive health in men and to treat DM-caused male sexual and reproductive dysfunction will be developed.
