Idiopathic impaired spermatogenesis: genetic epidemiology is unlikely to provide a short cut to better understanding

J Gianotten, PM Lombardi, AH Zwinderman, Richard Lilford, F van der Veen

Research output: Contribution to journalArticle

35 Citations (Scopus)


The aetiology of impaired spermatogenesis is unknown in the majority of subfertile men. From several studies of concordance for involuntary childlessness among men, we can conclude that there is a substantial familial component in male subfertility and that shared loci segregating through families can be assumed. We now know that deletions on the Y chromosome, which do not penetrate fully, account for some of these cases. There are good reasons to suspect that other cases result from mutations in genes located elsewhere in the genome. In this article, we discuss different approaches to unravelling the molecular basis of impaired spermatogenesis originating from genetic abnormalities in chromosomes other than the Y chromosome. Genetic mapping studies are in general a good approach to detect disease-causing genes that are segregating through a population; they can provide a short-cut to unravelling the biochemistry of a disease. In this paper, we explain our reasons for arguing that linkage and association studies are no promising means to identify the genes causing impaired spermatogenesis. We conclude that direct screening of candidate genes for mutations will be necessary to detect genes involved in impaired spermatogenesis. However, this approach requires studies of the biochemical pathways of normal and abnormal spermatogenesis. Since we have a poor understanding of these pathways, more research is needed into the biochemistry of spermatogenesis.
Original languageEnglish
Pages (from-to)533-539
Number of pages7
JournalHuman Reproduction
Issue number6
Early online date23 Sept 2004
Publication statusPublished - 31 Dec 2004


  • Y chromosome
  • gene mutations
  • spermatogenesis
  • male infertility
  • genetic epidemiology


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