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UCSF Researchers Find Evidence Of Faulty DNA Repair In Some Infertile Men

June 6, 2000
University Of California, San Francisco
Some infertile men have mutations or errors in their DNA code, suggesting that faulty DNA repair may be a reason for their infertility, according to UC San Francisco researchers.

Some infertile men have mutations or errors in their DNA code, suggesting thatfaulty DNA repair may be a reason for their infertility, according to UC SanFrancisco researchers.

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Moreover, this kind of DNA repair problem is similar to that found in certainkinds of cancer patients, and is linked to the abnormal growth of tumor cells.This finding has prompted the UCSF researchers to wonder if some infertile mencould pass the problem of faulty DNA repair to offspring conceived through hightechnology- assisted reproduction methods. If so, this could potentiallyincrease the risk of these children also being infertile, and might alsopredispose them to developing cancer, according to the researchers.

The research will be published in the June edition of the British journal HumanReproduction. The research, which was a small study of ten men, was performedin the laboratory of Renee Reijo Pera, MD, UCSF assistant professor in thedepartments of Obstetrics, Gynecology and Reproductive Sciences, Urology, HumanGenetics and Physiology.

"The conclusion is that some male infertility may be related to a largerproblem of defective DNA repair. This is encouraging news because it helps usexplain why some men are infertile. What is worrisome, though, is thatdefective DNA repair has a long association with cancer," said Paul Turek, MD,another study author and UCSF associate professor of urology. "The implicationsare that maybe infertility is not a minor problem. Maybe there is a very goodreason for men to be infertile."

Of all couples in America who are trying to conceive, 20 percent cannot, Tureksaid. Among those, half are due to male factor infertility. And many of thecases of male infertility are unexplained, Turek said. Common causes of maleinfertility include dilated veins in the scrotum (varicoceles), infections andtoxin exposure.

"A significant portion of the infertility we can't explain now is probablygoing to end up being genetic," Turek said. "That's a lot of people."

In addition, other researchers in the past have discovered that certaincancers, including a form of colon cancer, are associated with defective DNArepair. In 1995, the journal Cell published two papers in which the genesresponsible for DNA repair in mice were altered to see what happened. The micedeveloped tumors, as was expected. But the mice also became infertile, whichwas not expected.

"We wondered if infertile men with failing testicles that had a "look" similarto the testes from the altered mice would also show defective DNA repair,"Reijo Pera said. "We asked if the testis tissue of these infertile men showedcertain "fingerprints" characteristic of a problem repairing DNA."

The current UCSF study included five men with normally functioning testes andfive whose testes made little or no sperm, also called testes failure.Investigators sequenced testes tissue DNA from both groups and found anincreased frequency of certain DNA mutations or errors in the group with testesfailure. These men had 100-fold higher error rate in their DNA than the menwith normally functioning testes, Reijo Pera said.

This small study may help explain some cases of male infertility, but alsoraises several questions, Turek said. The findings need to be expanded toinclude many more infertile men to get a feel for the real impact of theresearch, he said.

Also, given what scientists know about defective DNA repair and cancer,researchers need to pay attention to what the consequences of this might be forinfertile couples, Turek said. One concern is the health of pregnancies andchildren conceived with assisted reproductive techniques, such asintracytoplasmic sperm injection (ICSI) in cases of male infertility due totestes failure. This precise technique helps couples with severe male factorinfertility have babies by injecting a single live sperm directly into thecenter of a human egg. The technique is very powerful because it can be usedwith sperm from the testes where they are made, as well as from the ejaculate.

"With ICSI, natural selection barriers that normally exist during conceptionmay be broken down. If a couple has a genetic problem, it may be transmitted tochildren in a way that might not occur normally." Turek said. "At this time, itis not at all clear whether a problem like this, that exists in the sex cellsof an infertile man, will be seen at all in his offspring if ICSI is used."

Perhaps problems with DNA repair will not be passed along to children conceivedthrough ICSI because such problems may simply result in miscarriages.Defective DNA repair is also commonly found in spontaneously aborted embryos,Reijo Pera said, suggesting babies who make it to term would not have thisproblem.

Alternatively, children with DNA repair defects may survive to term.Theoretically, they could then have an increased risk of infertility, orpossibly even tumor formation later in life, according to the study. "We don'tknow which scenario will be true." Turek said.

Turek said researchers should follow-up on the health and development of ICSIchildren in couples with severe male factor infertility from testes failure tohelp sort out these issues.

Other study authors are: David Nudell, MD, a surgeon-in-training in the UCSFDepartment of Urology and Michael Castillo, staff research associate in theUCSF Department of Obstetrics, Gynecology and Reproductive Sciences.

The study was funded by the National Institutes of Health, the University ofCalifornia Campus Laboratory Collaboration, UCSF-Stanford Healthcare and theCalifornia Urological Foundation.

Story Source:

The above story is based on materials provided by University Of California, San Francisco. Note: Materials may be edited for content and length.

Cite This Page:

University Of California, San Francisco. "UCSF Researchers Find Evidence Of Faulty DNA Repair In Some Infertile Men." ScienceDaily. ScienceDaily, 6 June 2000. <www.sciencedaily.com/releases/2000/06/000602073349.htm>.
University Of California, San Francisco. (2000, June 6). UCSF Researchers Find Evidence Of Faulty DNA Repair In Some Infertile Men. ScienceDaily. Retrieved March 30, 2015 from www.sciencedaily.com/releases/2000/06/000602073349.htm
University Of California, San Francisco. "UCSF Researchers Find Evidence Of Faulty DNA Repair In Some Infertile Men." ScienceDaily. www.sciencedaily.com/releases/2000/06/000602073349.htm (accessed March 30, 2015).

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