title: Linkage between male infertility and trinucleotide repeat expansion in the androgen-receptor gene.
abstract: BACKGROUND
  Androgens acting via the androgen receptor bring about stimulation and maintenance of spermatogenesis. If mutations in the androgen-receptor gene interfere with the receptor's function, this effect may partly account for impaired spermatogenesis. We aimed to find out whether expansion of a trinucleotide repeat in the androgen-receptor gene is associated with male infertility.
  
  
  METHODS
  We analysed 67 coded semen and blood samples from a predominantly white group of male infertility patients and controls. Clinical analyses included cause of infertility, sperm count, and reproductive hormone concentrations. Analysis of trinucleotide (CAG) repeat length and point mutations in the androgen-receptor gene was done by PCR, single-stranded conformational polymorphism, and DNA sequencing.
  
  
  RESULTS
  Screening and characterisation of the androgen-receptor gene in 35 patients and 32 controls showed no point mutations in the gene. 30 of the infertile patients had idiopathic azoospermia or oligozoospermia, and these men had significantly longer CAG repeat tracts than controls (mean 23.2 [SE 0.7] vs 20.5 [0.3], p=0.0001). The odds of having CAG repeat lengths of 20 were six-fold higher for fertile men than for men with a spermatogenic disorder.
  
  
  CONCLUSIONS
  Our results indicate a relation between CAG repeat length in the androgen-receptor gene and the risk of defective spermatogenesis. With the use of intracytoplasmic sperm injection, this mutation could be inherited, possibly leading to an increase in male infertility in future generations. Should further elongation of the CAG repeat occur in these future generations, there is an added risk of increased severity of male infertility, and potentially an increased incidence of neurodegenerative disease.
authors.affiliation: Institute of Reproduction and Development and Department of Mathematics and Statistics, Monash University, Monash Medical Centre, Victoria, Australia.
authors.forename: A T
authors.initials: AT
authors.lastname: Dowsing
authors.forename: E L
authors.initials: EL
authors.lastname: Yong
authors.forename: M
authors.initials: M
authors.lastname: Clark
authors.forename: R I
authors.initials: RI
authors.lastname: McLachlan
authors.forename: D M
authors.initials: DM
authors.lastname: de Kretser
authors.forename: A O
authors.initials: AO
authors.lastname: Trounson
mesh_terms: D000328:Adult; D005091:Exons / Q000235:genetics; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D009845:Oligospermia / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011944:Receptors, Androgen / Q000235:genetics*; D017422:Sequence Analysis, DNA; D019680:Trinucleotide Repeat Expansion
chemical_list: D011944:Receptors, Androgen