Abstract for presentation at 11th International Congress of Human Genetics

Meiotic chromosomal abnormalities in infertile men

  • Fei Sun, 1) Department of Medical Genetics, University of Calgary, Calgary, Canada; 2) Department of Genetics, Alberta Children’s Hospit, Canada
  • Evelyn Ko, Department of Genetics, Alberta Children’s Hospital, Calgary, Canada, Canada
  • Alfred Rademaker, Cancer Center, Northwestern University Medical School, Chicago, USA, United States
  • Calvin Greene, Department of Obstetrics and Gynecology, University of Calgary, Calgary, Canada, Canada
  • Paul Turek, Department of Urology and Reproductive Science, University of California at San Francisco, CA, USA, United States
  • Renée Martin, 1) Department of Medical Genetics, University of Calgary, Calgary, Canada; 2) Department of Genetics, Alberta Children’s Hospit, Canada

    • Purpose: Infertile men have an increased frequency of aneuploid sperm. We have determined that decreased recombination is associated with the production of aneuploid sperm in humans. The aim of this study was to determine if some cases of infertility are associated with decreased meiotic recombination.
    Methods: Analysis of the early stages of meiosis was performed in 36 men: 20 with nonobstructive azoospermia (NOA, no sperm in the ejaculate), 5 men with obstructive azoospermia (OA, mainly men with cystic fibrosis mutations) and 11 men with normal spermatogenesis. Newly-developed immunocytogenetic techniques were used to identify the synaptonemal complex (SC) in various stages of prophase. Antibodies to meiotic proteins identified the SC (SYN1/SCP3), the centromere (CREST) and recombination sites (MLH1). Approximately 100 spermatocytes were analyzed for each man.
    Results: All control donors and men with OA had pachytene cells. Of the 20 men with NOA, 9 had no meiotic cells, 1 man had cells blocked at zygotene and 10 men had cells in the pachytene stage. The mean frequency of recombination was 41.2 for men with NOA and 46.3 for men with OA, both significantly reduced compared to controls 48.0 (p<.0001, nested ANOVA). The percentage of cells with unsynapsed regions was 22.8% in men with NOA, 11.8% in OA, and 7.6% in controls (p = .06, Z test). The mean percentage of cells containing bivalents with no recombination foci was 35.3 in men with NOA, 10.2 in the OA group and 3.9 in controls (p<.05, Z test).
    Conclusions: A significant number of men with NOA have abnormalities in chromosome synapsis and an increased frequency of chromosomes with no recombination foci. In many cases of azoospermia, there is a significant decrease in the frequency of recombination. These meiotic abnormalities could lead to meiotic arrest or an increased frequency of aneuploid sperm.

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