Diabetes and the Impairment of Reproductive Function: Possible Role of Mitochondria and Reactive Oxygen Species

Abstract

Diabetes Mellitus (DM), a state of chronic hyperglycemia, is a major cause of serious micro and macrovascular diseases, affecting, therefore, nearly every system in the body. Growing evidence indicates that oxidative stress is increased in diabetes due to overproduction of reactive oxygen species (ROS) and decreased efficiency of antioxidant defences, a process that starts very early and worsens over the course of the disease. During the development of diabetes, oxidation of lipids, proteins and DNA increase with time. Mitochondrial DNA mutations have also been reported in diabetic tissues, suggesting oxidative stress-related mitochondrial damage. Diabetes-related oxidative stress may also be the trigger for many alterations on sexual function, which can also include decreased testicular mitochondrial function. Although sexual disorders have been extensively studied in diabetic men, possible changes in the sexual function of diabetic women have only recently received attention. The prevalence of sexual dysfunction in diabetic men approaches 50%, whereas in diabetic women it seems to be slightly lower. Testicular dysfunction, impotence, decreased fertility potential and retrograde ejaculations are conditions that have been described in diabetic males. Diabetes is also the most common cause of erectile dysfunction in men. Poor semen quality has also been reported in diabetic men, including decreased sperm motility and concentration, abnormal morphology and increased seminal plasma abnormalities. In addition, diabetic men may have decreased serum testosterone due to impaired Leydig cell function. Among diabetic women neuropathy, vascular impairment and psychological complaints have been implicated in the pathogenesis of decreased libido, low arousability, decreased vaginal lubrication, orgasmic dysfunction, and dyspareunia. An association between the production of excess radical oxygen species and disturbed embryogenesis in diabetic pregnancies has also been suggested. In fact, maternal diabetes during pregnancy is associated with an increased risk of complications in the offspring, such as altered fetal growth, polyhydramnios, fetal loss and congenital malformations. In addition, hypocalemia and reduced bone mineral content are found in neonates of diabetic mothers. Abnormalities in gametogenesis and sexual function have also been documented in animal models for both types of Diabetes, which thus constitute an important research tool to both study the effects of the disease, and to test novel therapeutical interventions. Because sexuality and fertility are important aspects in the lives of individuals and couples, and considering that over 124 million individuals worldwide suffer from Diabetes, this review highlights the impact of Diabetes and associated oxidative stress on sexual function.

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia

“…Paasch et al (2011) demonstrated higher expression levels of SPANX C, a isomer form of protein, in the sperm of diabetic and obese individuals [48]. This point may be clarified further by examining related studies that have shown poor semen quality accompanied by reduced sperm motility in diabetic individuals [49,50]. SPANX B might be related to energy production in spermatozoa; however further investigation is needed to clarify the exact function of this protein in sperm tail.…”

Gynura procumbens: An Overview of the Biological Activities

“…Aside from direct treatment of diabetes, research on G. procumbens has also explored its potential in treating infertility, which is one of the complications of diabetes (Ramalho-Santos et al, 2008). G. procumbens was found to exhibit an effect on sexual and reproductive function as the treatment with G. procumbens significantly increased sperm count, sperm motility, and reduced the percentage of sperm mortality of diabetic rats (Sani et al, 2008).…”

Modulation of diabetes-mellitus-induced male reproductive dysfunctions in experimental animal models with medicinal plants

“…[12] Studies have shown that men suffering from diabetes have sperms with greater DNA fragmentation and an increase in advanced glycation end products and their receptors (RAGE) leading to deterioration of sperm quality, sperm functions coupled with changes in testicular metabolite levels and spermatogenic gene expression. [192021] Several studies have shown that antioxidant treatment improves glycemic index, reduces diabetic complications, and protects components from oxidative damage. [2223]…”