Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion.

Submicroscopic deletions of the Y chromosome and polymorphisms of the androgen receptor (AR) gene in the X chromosome have been observed in men with defective spermatogenesis. To further define the subregions/genes in the Y chromosome causing male infertility and its relationship to polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of 202 subfertile males and 101 healthy fertile controls of predominantly Chinese ethnic origin. Y microdeletions were examined with 16 sequence-tagged site (STS) probes, including the RBM and DAZ genes, spanning the AZFb and AZFc subregions of Yq11, and related to the size of trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions were detected and confirmed in three out of 44 (6.8%) of azoospermic and three out of 86 (3.5%) severely oligozoospermic patients. No deletions were detected in any of the patients with sperm counts of >0.5 x 10(6)/ml, nor in any of the 101 fertile controls. All six affected patients had almost contiguous Y microdeletions spanning the entire AZFc region including the DAZ gene. The AZFb region, containing the RBM1 gene, was intact in five of the six subjects. Y deletions were not found in those with long AR polyglutamine tracts. Our study, the first in a Chinese population, suggest a cause and effect relationship between Y microdeletions in the AZFc region (possibly DAZ), and azoospermia or near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear to be independent contributors to male infertility.

[1]  M. Mitchell,et al.  Characterisation of the coding sequence and fine mapping of the human DFFRY gene and comparative expression analysis and mapping to the Sxrb interval of the mouse Y chromosome of the Dffry gene. , 1998, Human molecular genetics.

[2]  F. Ghadessy,et al.  Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. , 1997, The Journal of clinical endocrinology and metabolism.

[3]  E. Salido,et al.  Multiple functional copies of the RBM gene family, a spermatogenesis candidate on the human Y chromosome. , 1997, Genomics.

[4]  J. Siffroi,et al.  Assisted reproductive technology and complex chromosomal rearrangements: the limits of ICSI. , 1997, Molecular human reproduction.

[5]  M. Ruggiu,et al.  The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis , 1997, Nature.

[6]  A. Mielnik,et al.  Submicroscopic deletions in the Y chromosome of infertile men. , 1997, Human reproduction.

[7]  J. Horst,et al.  The molecular genetics of male infertility. , 1997, Molecular human reproduction.

[8]  P. Vogt,et al.  Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  C. Foresta,et al.  Y-chromosome deletions in idiopathic severe testiculopathies. , 1997, The Journal of clinical endocrinology and metabolism.

[10]  L. Hoefsloot,et al.  Microdeletions of the Y chromosome and intracytoplasmic sperm injection: from gene to clinic. , 1997, Human reproduction.

[11]  B. Dworniczak,et al.  Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia. , 1997, Fertility and sterility.

[12]  A. V. van Bergen,et al.  Microdeletions in the Y chromosome of infertile men. , 1997, The New England journal of medicine.

[13]  D. Page,et al.  Expression of DAZ, an azoospermia factor candidate, in human spermatogonia. , 1997, American journal of human genetics.

[14]  A. Agulnik,et al.  Absence of DAZ gene mutations in cases of non-obstructed azoospermia. , 1997, Molecular human reproduction.

[15]  E. Salido,et al.  The human autosomal gene DAZLA: testis specificity and a candidate for male infertility. , 1996, Human molecular genetics.

[16]  S. Rozen,et al.  The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned , 1996, Nature Genetics.

[17]  H. Cooke,et al.  Polymerase chain reaction screening for Y chromosome microdeletions: a first step towards the diagnosis of genetically-determined spermatogenic failure in men. , 1996, Molecular human reproduction.

[18]  A. Edelmann,et al.  Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. , 1996, Human molecular genetics.

[19]  D. Page,et al.  Severe oligozoospermia resulting from deletions of azoospermia factor gene on Y chromosome , 1996, The Lancet.

[20]  P. Yen,et al.  Substantial prevalence of microdeletions of the Y-chromosome in infertile men with idiopathic azoospermia and oligozoospermia detected using a sequence-tagged site-based mapping strategy. , 1996, The Journal of clinical endocrinology and metabolism.

[21]  R. Tenaglia,et al.  Microdeletions in interval 6 of the Y chromosome detected by STS-PCR in 6 of 33 patients with idiopathic oligo- or azoospermia. , 1996, Cytogenetics and cell genetics.

[22]  S. Rozen,et al.  Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA–binding protein gene , 1995, Nature Genetics.

[23]  F. S. French,et al.  Androgen receptor defects : Historical, clinical, and molecular perspectives , 1995 .

[24]  Y. Nakahori,et al.  PCR analysis of the Y chromosome long arm in azoospermic patients: evidence for a second locus required for spermatogenesis. , 1995, Human molecular genetics.

[25]  S. Ratnam,et al.  Pregnancy after hormonal correction of severe spermatogenic defect due to mutation in androgen receptor gene , 1994, The Lancet.

[26]  N. Chamberlain,et al.  The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. , 1994, Nucleic acids research.

[27]  S. Ratnam,et al.  Complete androgen insensitivity due to a splice-site mutation in the androgen receptor gene and genetic screening with single-stranded conformation polymorphism. , 1994, Fertility and sterility.

[28]  Howard J. Cooke,et al.  A Y chromosome gene family with RNA-binding protein homology: Candidates for the azoospermia factor AZF controlling human spermatogenesis , 1993, Cell.

[29]  P. Goodfellow,et al.  The role of the sex-determining region Y gene in the etiology of 46,XX maleness. , 1993, The Journal of clinical endocrinology and metabolism.

[30]  P. Beer-Romero,et al.  The human Y chromosome: a 43-interval map based on naturally occurring deletions. , 1992, Science.

[31]  D. Page,et al.  The human Y chromosome: overlapping DNA clones spanning the euchromatic region. , 1992, Science.

[32]  P. McDonough,et al.  Evidence for a partial deletion in the androgen receptor gene in a phenotypic male with azoospermia. , 1991, American journal of obstetrics and gynecology.

[33]  H. Burger,et al.  Variable androgen receptor levels in infertile men. , 1987, The Journal of clinical endocrinology and metabolism.

[34]  B. Czepulkowski,et al.  Human cytogenetics : a practical approach , 1986 .

[35]  J. Griffin,et al.  The frequency of androgen receptor deficiency in infertile men. , 1982, The Journal of clinical endocrinology and metabolism.

[36]  R Eliasson,et al.  Laboratory manual for the examination of human semen and semen-cervical mucus interaction. , 1980 .