Sperm DNA Is Damaged in Diabetics

BELFAST, May 4 -- Men with diabetes have sperm that exhibited greater DNA damage than with non-diabetics' sperm, researchers here said.

The damage was seen in both nuclear DNA and in the DNA of the mitochondria, according to Ishola Agbaje, M.D., of Queen's University and colleagues.

Because the incidence of type II diabetes is increasing, the finding could have population-wide consequences for male fertility, Dr. Agbaje noted online in Human Reproduction.

"As far as we know, this is the first report of the quality of DNA in the nucleus and mitochondria of sperm in diabetes," he said.

Co-author Sheena Lewis, Ph.D., also of Queen's, noted that the finding is important from a clinical perspective, "particularly given the overwhelming evidence that sperm DNA damage impairs male fertility and reproductive health."

The researchers performed conventional semen analysis -- including semen volume, sperm count, motility, and morphology -- on 27 men with diabetes and a control group of 29 non-diabetic men undergoing routine infertility investigations.

They also assessed nuclear DNA fragmentation and deletions in mitochondrial DNA, Dr. Agbaje and colleagues reported.

The conventional semen analysis found:

• There was a small but statistically significant reduction in semen volume in diabetic men (2.6 mL compared with 3.3 mL) for the control group. The difference was significant at P<0.05.
• Other parameters did not differ significantly.

When it came to the single cell gel electrophoresis assay (or Comet assay), however, the researchers found significantly more nuclear DNA fragmentation in the diabetic volunteers than in the controls.

Specifically, 53% of diabetic DNA was fragmented, on average, compared with 32% of control DNA, a difference that was statistically significant at P<0.0001.

The researchers also found that the median number of deletions in mitochondrial DNA -- assessed using a technique called Long-PCR -- was higher in the diabetic men.

Specifically, the median number of deletions was four (with a range from three to six) in the diabetic men compared with three (with a range from one to four) in the controls. The difference was significant at P<0.05.

Dr. Agbaje and colleagues acknowledged that the control group is probably not representative of the general population, because the men were recruited from those attending a fertility clinic.

But, they said, any differences are likely to be even greater when diabetic men are compared with normally fertile men.

"Given the association between infertility and both [nuclear and mitochondrial] DNA damage, one would reasonably expect these men, if anything, to be biased towards a higher level of [nuclear] DNA fragmentation," the researchers said.

One implication of the study is that the partners of diabetic men may be more prone to miscarriage, Dr. Lewis noted.

"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," she said.

But it's still not clear whether the DNA damage caused by diabetes would have the same effect on fertility as damage caused by such things as smoking, she said.

"This is just one relatively small study that highlights a possible concern," Dr. Lewis noted, adding that further research is needed to tease out the nature of the damage, what causes it, and its clinical implications.