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First research to show that diabetes damages DNA in men's sperm and may affect fertility

May 03, 2007

Scientists have found that sperm from diabetic men have greater levels of DNA damage than sperm from men who do not have the disease. They warn that such DNA damage might affect a man's fertility.

In the first study [1] to compare the quality of DNA in sperm from diabetic and non-diabetic men, the researchers from Belfast, Northern Ireland showed that the DNA in the nuclei of the sperm cells had greater levels of fragmentation in diabetic men (52%, versus 32% in non-diabetic men), and that there were more deletions of DNA in the tiny, energy-generating structures in the cells called mitochondria (4 versus 3).

Dr Ishola Agbaje, who undertook the research published online today (Thursday 3 May) in the journal Human Reproduction, said: "As far as we know, this is the first report of the quality of DNA in the nucleus and mitochondria of sperm in diabetes. Our study identifies important evidence of increased DNA fragmentation of nuclear DNA and mitochondrial DNA deletions in sperm from diabetic men. These findings cause concern, as they may have implications for fertility."

The incidence of type 1 and type 2 diabetes is increasing rapidly worldwide. While diet and obesity are known to be key factors in the increase of type 2 (or late onset) diabetes, type 1 diabetes which is usually diagnosed in childhood or adolescence, is increasing by three per cent a year in European children, although the reason for this is not entirely clear. Genetic factors that make people more susceptible, or environmental factors such as viruses that may trigger the onset of type 1 diabetes, could play a role.

Dr Agbaje, a research fellow in the Reproductive Medicine Research Group at Queen's University, Belfast, said: "If the increasing trend in the incidence of type I diabetes continues, this will result in a 50% increase over the next ten years. As a consequence, diabetes will affect many more men prior to and during their reproductive years. Infertility is already a major health problem in both the developed and developing world, with up to one in six couples requiring specialist investigation or treatment in order to conceive. Moreover, the last 50 years have seen an apparent decline in semen quality. Sperm disorders are thought to cause or contribute to infertility in 40-50% of infertile couples. The increasing incidence of systemic diseases such as diabetes may further exacerbate this decline in male fertility. However, it is not clear to what extent clinics consider information about the diabetic status of their patients when investigating fertility problems." [2]

Dr Agbaje and his colleagues examined sperm from 27 diabetic men, with an average age of 34, and 29 non-diabetic men with an average age of 33. They found that although semen volume was significantly less in diabetic men (2.6 versus 3.3 ml), there were no significant differences in sperm concentration, total sperm output, form and structure of the sperm or their ability to move. When they measured DNA damage they found that the percentage of fragmented nuclear DNA was significantly higher in sperm from the diabetic men and that the number of deletions in mitochondrial DNA was also higher - the number of deletions ranged from three to six (average four) in the diabetic men and from one to four (average three) in the non-diabetic men.

Professor Sheena Lewis, scientific director of the Reproductive Medicine Research Group, said: "Our study shows increased levels of sperm DNA damage in diabetic men. From a clinical perspective this is important, particularly given the overwhelming evidence that sperm DNA damage impairs male fertility and reproductive health. Other studies have already shown that, while the female egg has a limited ability to repair damaged sperm DNA, fragmentation beyond this threshold may result in increased rates of embryonic failure and pregnancy loss. In the context of spontaneous conception, sperm DNA quality has been found to be poorer in couples with a history of miscarriages."

However, Prof Lewis said that it was not possible to say from this current study whether the DNA damage caused by diabetes would have the same effect on men's fertility and the health of future children as DNA damage caused by other factors such as smoking.

"This is just one, relatively small study that highlights a possible concern. Further studies need to be carried out in order to understand the precise nature of the diabetes-related damage, the causal mechanisms and the clinical significance. Given the global rise in the prevalence of diabetes, it is also vital to examine the reproductive outcomes of pregnancies fathered by diabetic men, and the prevalence of diabetes amongst men attending for infertility treatment," she concluded.
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[1] Insulin dependent diabetes mellitus: implications for male reproductive function. Human Reproduction. doi:10.1093/humrep/dem077.

[2] Studies have estimated the prevalence of diabetes in sub-fertile men as 1% - three times more than expected (0.3%), given the prevalence of diabetes and male infertility in the general population. This suggests that diabetes is having a significant impact on male fertility.

European Society for Human Reproduction and Embryology