Human Molecular Genetics Advance Access first published online on September 22, 2004
This version published online on October 1, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh302
© 2004 by Oxford University Press
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1 Center for Reproductive Sciences; Department of Obstetrics, Gynecology and Reproductive Sciences; Department of Urology; University of California at San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0556, USA; Department of Physiology; Programs in Human Genetics, Cancer Genetics, and Developmental and Stem Cell Biology; University of California at San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0556, USA
* To whom correspondence should be addressed. E-mail: reijo{at}itsa.ucsf.edu.
Two percent of men are infertile due to defects in sperm production. In 10-15% of cases, Y chromosome deletions that encompass critical spermatogenesis genes are detected; in the remaining cases, the cause of infertility is unknown. In model organisms, defects in recombination genes cause infertility, germ cell aneuploidy and subsequent development of inviable or abnormal progeny. Several studies have also linked infertility and higher rates of germ cell aneuploidy in men and women. Thus, we reasoned that defective recombination may be a major cause of infertility in men with poor or no sperm production and we performed the first comparison of recombination parameters within populations of single spermatocytes from infertile and fertile men who reported for assisted reproduction. We observed that 10% of nonobstructive azoospermic men had significantly lower recombination frequencies than men with normal spermatogenesis. Furthermore, when we focused our analysis only on those men who had a pathological diagnosis of "maturation arrest" due to arrest during sperm development, about half had detectable defects in recombination. In contrast, none of the men with normal spermatogenesis had defects in recombination. Thus, this study provides direct evidence that defects in recombination are linked to poor sperm production in a significant percentage of infertile men. Implications of this observation for the use of assisted reproductive technologies are especially relevant to consider given that recombination is required to both introduce genetic variation and to insure proper chromosome separation during meiosis.
Article
Defective recombination in infertile men
2 Department of Medical Genetics, Faculty of Medicine, University of Calgary, Alberta, T2 5C7, Canada; Department of Genetics, Alberta Children's Hospital,1820 Richmond Road SW, Calgary, Alberta, T2T 5C7, Canada
3 Department of Urology, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA; Center for Biomedical Research, The Population Council, New York, NY 10021, USA
4 Center for Reproductive Sciences; Department of Obstetrics, Gynecology and Reproductive Sciences; Department of Urology; University of California at San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0556, USA
5 Department of Obstetrics and Gynecology, Faculty of Medicine, University of Calgary, Alberta, T2N 4N1, Canada
Abstract
The originally published version of this paper was the pre-revision version and should be disregarded.
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