Abstract:Diabetes mellitus is a group of lifelong metabolic diseases characterized by chronic hyperglycemia caused by multiple etiologies. According to relevant statistics, there are more than 100 complications of diabetes, which is a chronic disease with the most known complications. Previous studies have shown that diabetes not only affects male fertility by causing sexual hormone secretion disorders and reducing spermatogenesis in the testes, but diabetes may also cause erectile dysfunction in men, thereby reducing male fertility. The sharp decline in the current fertility rate is also closely related to infertility caused by various reasons, and among them, male infertility is one of the major problems. According to the data from the National Bureau of Statistics, the infertility rate of couples of childbearing age in my country has risen to 12%-18%, and infertility caused by male factors accounts for 50% of them. Therefore, it is necessary to explore the relationship between diabetes and male fertility.
Diabetes affects male reproductive health and can cause severe or infertility
Type 1 diabetes may affect male fertility, gonadal axis, semen parameters, and spermatogenesis due to the effects of hyperglycemia and insulin deficiency. And animal and in vitro studies have shown that insulin is important for gonadal function and spermatogenesis, and insulin deficiency is a hallmark of type 1 diabetes and may therefore affect male gonadal function.
Researchers conducted a retrospective analysis of literature published between January 1980 and December 2020 to clarify the relationship between type 1 diabetes and male fertility. They found that type 1 diabetes patients, especially those with prolonged disease, had lower natural fertility rates than controls. The related research results were published in Andrology under the title “The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis”.
Figure 1 Research results (Source: )
In this study, researchers identified “Type 1 Diabetes,” “Insulin-Dependent Diabetes,” “Young Diabetics and Male Fertility,” “Male Infertility,” ” Semen parameters” and other keywords, collected and analyzed relevant literature from January 1980 to December 2020, and compared the fertility of men with type 1 diabetes and healthy men.
In four of the studies evaluating the effect of type 1 diabetes on male natural fertility, Schiavi et al found the mean natural fertility rate in the diabetes group to be 2.5 (range 0-4), Holstein et al found that more than 50% of men with type 1 diabetes were childless, Sjöberg et al. found that men with diabetes had lower live birth rates than controls, and Wiebe et al. found diagnosed earlier than controls Men with diabetes had significantly lower proportions of children, that is, men with childhood onset had significantly lower fertility.
Nine studies that analyzed semen parameters in men with type 1 diabetes showed that type 1 diabetes patients had lower semen volume, total sperm count and motility than controls;1 Patients with type 1 diabetes have poor sperm morphology; patients with type 1 diabetes have poor sperm motility and a high number of defective sperm; sperm from patients with type 1 diabetes have more sperm nuclear DNA fragments and mitochondrial DNA deletions; The proportion of spermatozoa with abnormal mitochondrial function increased in patients aged 2000.
Combining the above studies, there is evidence that Type 1 diabetes may affect male reproductive health at various levels, including functional sperm changes that ultimately lead to reduced fertility. However, the mechanism by which type 1 diabetes impairs male fertility remains unclear and further research is needed.
Cordycepin ameliorates diabetes-induced testicular damage through Sirt1/Foxo3a pathway
The previous section mentioned that diabetes has a negative impact on male reproductive health. How can this negative impact be improved? Studies have shown that cordycepin, an extract of Cordyceps sinensis, can protect the integrity of the blood-testis barrier, inhibit cell apoptosis, and resist oxidative stress, and may play an effective therapeutic role in diabetes-induced testicular damage in men .
Researchers from some Chinese universities tried to discover the protective mechanism of cordycepin on testicular damage caused by hyperglycemia through research. Amelioratesdiabetes-induced testicular damage through the Sirt1/Foxo3a pathway” was published in Andrologia. They found that cordycepin could ameliorate hyperglycemia-induced testicular damage, restore blood-testis barrier, and improve spermatogenesis by regulating downstream antioxidant enzyme activity through SIRT1/Foxo3a signaling pathway.
Figure 2 Research results (Source: )
Sirtuin 1 (SIRT1), the first family of Sirtuin proteins discovered, is a key NAD+-dependent deacetylase in mammals. Studies have shown that SIRT1 can directly or indirectly regulate the activity of Foxo transcription factors through deacetylation. In particular, SIRT1 can deacetylate Foxo3a to enhance the ability to resist oxidative stress, which may be the most important potential target of diabetic complications. Furthermore, some studies have shown a broad association between SIRT1 and testicular cell activity. Therefore, finding a natural, safe and effective SIRT1 activator is crucial for preventing diabetes-induced testicular damage.
In this study, a diabetes model was established by feeding C57BL/6 male mice a high-fat diet for 4 weeks, and injecting 50 mg/kg streptozotocin intraperitoneally for 5 consecutive days. blood glucose levels in mice, and studies were conducted using mice with blood glucose levels greater than 16.7 mmol/L. Mice in the normal group received standard diet and intraperitoneal injection of normal saline for 5 days. Diabetic mice were divided into three groups and were given saline, 10 mg/kg cordycepin, and 20 mg/kg cordycepin, respectively. After 8 weeks of treatment, these mice were analyzed.
■ Cordycepin attenuated diabetes-induced testicular damage in mice, Cordycepin significantly reversed the decline in testicular volume and testicular index in mice, and cordycepin-treated group Significantly increased sperm concentration and inhibited sperm head and tail deformity rate;
■Cordycepin restores blood-testis barrier damage caused by hyperglycemia;
■Cordycepin inhibited diabetes-induced apoptosis of testicular cells;
■Cordycepin can prevent diabetes-induced testicular oxidative stress, MDA levels in testis tissue of all cordycepin-treated mice were significantly lower than the untreated diabetes group;
■Cordycepin plays a protective role mainly by stimulating antioxidant enzymes in the testis through the SIRT1/Foxo3a pathway.
According to data released by the International Diabetes Federation, in 2019, 1 in 11 adults aged 20 to 79 in the country had diabetes, and by 2045, this number is expected to increase will increase to 700 million. With the increasing incidence of diabetes and the limitation of treatment strategies, testicular damage caused by diabetes has become a major threat to male reproductive health worldwide.
In this article, we mentioned that cordycepin may improve testicular damage caused by diabetes, thereby protecting male fertility from damage. However, the magnitude of its effect has not yet been verified. Coupled with the particularity of each individual’s condition, the protective effect of cordycepin on each patient remains to be discussed.
Writing | Mu Zijiu
Facondo P, Di Lodovico E, Delbarba A, et al. The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis. Andrology. 2022 Mar;10 (3):426-440. doi: 10.1111/andr.13140. Epub 2021 Dec 22. PMID: 34904793.
Huang T, Zhou Y, Lu X, et al. Cordycepin, a major bioactive component of Cordyceps militaris, ameliorates diabetes-induced testicular damage through the Sirt1/Foxo3a pathway. Andrologia. 2022 Feb;54(1):e14294. doi: 10.1111/and.14294. Epub 2021 Nov 22. Erratum in: Andrologia. 2022 Jul;54(6):e14430. PMID: 34811786.
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