Mol. Hum. Reprod. Advance Access originally published online on July 22, 2005
Molecular Human Reproduction 2005 11(7):507-512; doi:10.1093/molehr/gah191
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The Y chromosome gr/gr subdeletion is associated with male infertility
1Prince Henry’s Institute of Medical Research, 2Monash Immunology and Stem Cell Laboratories, Monash University, 3Monash IVF, 4Monash Institute of Medical Research, Monash University, 5ARC Centre of Excellence in Biotechnology and Development, 6University of Melbourne, Department of Obstetrics and Gynaecology, Royal Women’s Hospital, Carlton and 7Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre, Clayton, Victoria, Australia
8 To whom correspondence should be addressed at: Prince Henry’s Institute of Medical Research, P.O.Box 5152, Clayton, 3168, Victoria, Australia. E-mail: rob.mclachlan{at}phimr.monash.edu.au
Men with Y chromosome (Yq) AZFc deletions lack all copies of the DAZ gene and have severe spermatogenic failure. A recently described gr/gr subdeletion of AZFc removes two of four copies of DAZ. To better understand the relative frequencies of AZFc and gr/gr deletions and their associated phenotypes, we analysed two large groups of infertile men. A total of 788 men from the Monash Male Infertility (MMI) database with a range of fertility disorders showed similar overall prevalences of AZFc (2.5%) and gr/gr deletions (3.4%). There was no association of gr/gr deletions with sperm density. In 234 control men of known or presumed fertility, only one gr/gr deletion was found. In a further 599 consecutive men presenting for assisted reproductive technologies, we detected 13 (2.2%) AZFc deletions and 28 (4.7%) gr/gr deletions. All AZFc deletions were seen with sperm densities <5 million/ml but again the gr/gr deletion occurred with similar frequency across all sperm density categories. These data show that gr/gr deletions are significantly associated with infertility in the Australian population (P = 0.0015) but not exclusively with reduced sperm density suggesting a complex interaction with other factors important for male fertility. Vertical transmission of gr/gr deletions from father to son by ICSI was demonstrated in four cases. Analysis of 130 ICSI-conceived sons revealed no de novo gr/gr deletions indicating that ICSI is not a risk factor. The data suggest that testing for gr/gr deletions should be considered in the routine genetic assessment of men with idiopathic infertility.
Key words: deletion/male infertility/spermatogenic failure/Y chromosome
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