Defective recombination in infertile men

Hum Mol Genet. 2004 Nov 15;13(22):2875-83. doi: 10.1093/hmg/ddh302. Epub 2004 Sep 22.


Two percent of men are infertile owing 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 non-obstructive 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 insure proper chromosome separation during meiosis.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Female
  • Fertilization in Vitro
  • Humans
  • Karyotyping
  • Male
  • Meiosis
  • Oligospermia / genetics*
  • Oligospermia / pathology
  • Pregnancy
  • Recombination, Genetic*
  • Spermatogenesis
  • Spermatozoa / metabolism
  • Spermatozoa / pathology