Scientists Uncover a New, Genetic Cause of Male Infertility—And It Appears to be Widespread

By Veronique Greenwood | July 21, 2011 9:38 am

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What’s the News: What if the egg is fine and the sperm is dandy, but you still can’t seem to have a baby? Couples who are having trouble conceiving can testify to the frustration of learning that there’s no clear reason for their infertility. Now, however, scientists have found a genetic mutation that makes outwardly normal sperm much less fertile, potentially explaining many such cases and suggesting new routes to conception.

What’s the Context:

  • Infertility is defined as failure to conceive after a year of unprotected sex. About 10-15% of couples run into this problem.
  • Some cases of infertility are fairly easily explained: there may be a shortage of sperm, or they may be unable to swim far enough to make it to the egg. The eggs in turn may be malformed, or the womb may have conditions that make implantation of the fertilized egg difficult. But in about 20% of infertile couples, it’s not clear what is impeding the process.
  • When treating infertility, knowing the source of the problem is a big help. For instance, if the problem is the number of sperm, one option is concentrating sperm into a single sample and trying with that. But if the problem is with the womb, then in vitro fertilization, where eggs are fertilized by sperm in a Petri dish and then implanted, might be a better option.

How the Heck:

  • The scientists investigated a mutant variant of the gene for DEFB126, a protein that’s found on the membrane of sperm cells. Due to a mix-up with a genetic stop sign, this variant produces a protein that’s longer than the normal version.
  • Humans have two copies of each gene, one from each parent. When both of a man’s copies of a gene had the mutation, the cells’ quality control mechanisms seemed to destroy most of the proteins, and sperm had correspondingly fewer of them on their surfaces, though they seemed otherwise perfectly healthy. But when the scientists tried to get them to swim through a laboratory version of cervical mucus, nearly all of them stalled and got stuck. The more protein a sperm had, the more likely it was to swim through.
  • To see if this gene variant was related to infertility in real life, the scientists then tracked about 500 newlywed couples for two years. They found that couples in which the man had the mutation in both genes, the woman was significantly less likely to get pregnant. While this relationship will need to be backed up by more studies, it’s intriguing.
  • No current test for male infertility, the researchers point out, would alert men of this problem.

The Future Holds:

  • How exactly would this variant cause infertility? In monkeys, the normal protein is known to help sperm get through cervical mucus, keep sperm safe from the female’s immune system, and aid in sperm’s attachment to the fallopian tubes. If having this mutant version impedes any one of those processes, it could contribute to a couple’s inability to get pregnant.
  • Figuring out what is going on could suggest treatments for infertility caused this way—for instance, sperm could be supplied with normal versions of the protein, or couples, once alerted to the problem, could go straight to in vitro fertilization instead of trying other methods that rely on the robustness of sperm.
  • What’s incredibly strange about this discovery, though, is that this variant is common. So common, in fact, that about 20% of the population seems to have it, judging from the scientists’ analysis of genetic databases. That seems to indicate that being heterozygous for the variant—having one normal gene and one mutant one, as many men do—might have some evolutionary benefit, like resistance to disease, that, on the level of the population, counterbalances the apparent infertility caused by having two copies of it. At this point any such explanations are purely speculative, but for geneticists, this promises to be a fascinating knot to untangle.

Reference: T. L. Tollner, S. A. Venners, E. J. Hollox, A. I. Yudin, X. Liu, G. Tang, H. Xing, R. J. Kays, T. Lau, J. W. Overstreet, X. Xu, C. L. Bevins, G. N. Cherr, A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. Sci. Transl. Med. 3, 92ra65 (2011).

Image credit: Santa Rosa OLD SKOOL / flickr

CATEGORIZED UNDER: Health & Medicine
  • AG

    To fight such natural selection in our own speciese, are we helping our own kind?

  • TerryEmberson

    Natural selection brought us brains. This is using them. It helps prove the our fitness of our species.

  • Sieben Stern

    Fitness of our species until we overpopulate the world and all go to heck in a hand basket. Oh, wait….

  • Fred

    What part of the world are the newly wed from and what are their family histories. These are the next set of questions we should be asking. Then the next step would be trying to correct the gene or asking if these people should be helped and letting nature take place.

  • vickie98531

    Fred, you’re correct in your statement that the newlyweds need further testing, absolutely!
    However, before we run off modifying something else that Nature took forever to create, we would be well advised to learn as much of its function as we possibly are able. If Nature herself say fit to leave it in functioning order for all this time, its job must be pretty important.

  • Alyson

    I agree with those who are underwhelmed that we have found a possible cause of lower fertility. Im curious, scientifically, as to how the mechanism works, and why it may have been selected for in large enough numbers to end up in 20% of males, but I really, really could care less about treating the infertile. We are overpopulated, and it seems beyond ridiculous to me that science just keeps trying to find ways to make overpopulation work, rather than just acknowledge that many of the worlds problems could be solved, cheaply and easily, with birth control.

  • mrboma

    This article gets infertility treatments wrong. First of all, they do test for compatibility between sperm and cervical mucous. Intra-Uterine Insemination (IUI) is not “concentrating sperm into a single sample and trying with that.” The woman is given mild fertility drugs leading up to the IUI in order to produce between 1 and 3 extra eggs for that cycle and then is given a trigger shot to get all of the follicles to ovulate at about the same time. The sperm is taken from a single ejaculation, cleaned and concentrated, and then injected by catheter directly into the uterus, bypassing the possibly problematic cervical mucous. If IUI fails after 3 attempts (success rate is ~15%), then IVF is tried (with a success rate also around 15%). In other words, this discovery does nothing to change this protocol, because the mucous/sperm compatibility issue is already addressed.

  • http://DiscoverMagazine Templar 7

    Ahhh….more beautiful evidence twords my arguement that too many people mix up Evolution and Mutation. Mutation is more than the Metagenetical role that the THEORY of Evolution puts it in and one day people will wake up and realize Darwin was actually pretty stupid and insecure in his own work.

    Good day

  • Mike

    They are putting something in the vaccines!!!

  • Hoodydothen

    Templar 7 has problems with the dictionary, reading research, shooting off ‘er yap, explaining who she’s talking about…. Clears up, though!

    It’s a fine contraceptive; go read the paper and a bit on the type of mutation, then tell us whether it’s from vaccine and/or disease genome interaction, too much salt, or mass-produced chocolate.

    Love the comment about the tribe, the ‘newly wed.’ I think there are links to the ‘goyim’ tribe….

  • http://www.custom-wheels-car-rims.com/ car rims

    I used to be recommended this web site through my cousin. I am no longer sure whether or not this submit is written via him as nobody else recognise such certain about my difficulty. You’re wonderful! Thanks!

  • http://livetradingroom.forexaddict.info live trading room

    among billions of sperm, we’re born and we won the battle to be in this world today. You were born to win, because you already won your first battle!

  • Matt B.

    I have to argue with definitions such as “failure to conceive after a year of unprotected sex”. The frequency of copulation would have to be a factor. This problem is also present in specs on contraceptives. Are the people having sex every day, once a week, once a month…?

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