J.H.A.M. Tuerlings

Is increased CAG repeat length in the androgen receptor gene a risk factor for male subfertility

PURPOSE Increased length of the CAG repeat in the androgen receptor gene may be related to male subfertility. Expansion to 38-62 CAG repeats leads to the neurodegenerative disorder with male infertility called Kennedys disease. Recently it was suggested that slight expansion is related to male subfertility. In this study we investigated the association of male subfertility with the length of CAG repeats in the androgen receptor. MATERIALS AND METHODS CAG repeat length in the androgen receptor gene was investigated in 75 subfertile men, who were mainly candidates for intracytoplasmic sperm injection. Sperm parameters varied from azoospermia to severe oligoasthenoteratozoospermia. The control group consisted of 70 men who predominantly had bladder cancer. DNA was isolated from peripheral blood and genotyping was performed with polymerase chain reaction based methods. RESULTS No statistically significant difference in the mean length of the CAG repeat plus or minus standard deviation was noted in subfertile men and controls (22.2 +/- 3.1 and 21.7 +/- 3.4, respectively). The length of the CAG repeat in the androgen receptor was not related to the degree of impaired spermatogenesis or clinical characteristics of the subfertile men. CONCLUSIONS Increased length of CAG repeats in the androgen receptor gene is not a risk factor for male subfertility.

Y-chromosomal DNA haplotypes in infertile European males carrying Y-microdeletions.

We have determined Y-chromosomal DNA haplotypes in 73 infertile European males carrying Y microdeletions and compared them with the haplotypes of 299 infertile males lacking microdeletions. Chromosomes were typed with a set of 11 binary Y markers, which identified 8 haplogroups in the sample. Haplogroup frequencies were compared between 3 microdeletion classes and the non-deleted infertile males. Deletions arise on many different haplotypic backgrounds. No statistically significant differences in frequency were seen, although the small number of AZFa deletions lay predominantly on one branch of the Y haplotype tree.

Familial oligoasthenoteratozoospermia: evidence of autosomal dominant inheritance with sex-limited expression

OBJECTIVE To report the familial occurrence of severe oligoasthenoteratozoospermia in a man and five male relatives related through their mothers. DESIGN Case report. SETTING University medical center. PATIENT(S) Six affected family members. MAIN OUTCOME MEASURE(S) Blood and semen samples were collected from all affected males and some of their healthy male relatives. Pedigree analysis and exclusion of X-linked disorder were done. RESULT(S) Analysis suggested that familial nonsyndromic male factor infertility was present. CONCLUSION(S) The family described in this report suggests the existence of an autosomal dominant trait of male infertility with sex-limited expression.

DAZLA: an important candidate gene in male subfertility?

AbstractPurpose: To study the role of the autosomal candidate gene DAZLA (Deleted in AZoospermia Like Autosome) in male subfertility. Methods: We reviewed clinical data of subfertile men with oligozoospermia or azoospermia, mostly candidates for intracytoplasmic sperm injection (ICSI). Mutation detection was performed using polymerase chain reaction followed by single strand conformation polymorphism analysis. All shifted bands were analyzed by sequencing. Results: We searched for mutations in 44 subfertile men. Nine subfertile men were included, because family history showed that their brothers also faced fertility problems. In these men a possible autosomal gene defect may contribute to their fertility problem. No mutations were found, except for two polymorphisms in intron 4 and 5. Conclusion: At this moment it does not seem relevant to search for possible mutations in the DAZLA gene in clinical practice.

Erratum to: Y-chromosomal DNA haplotypes in infertile European males carrying Y-microdeletions

We have determined Y-chromosomal DNA haplotypes in 73 infertile European males carrying Y microdeletions and compared them with the haplotypes of 299 infertile males lacking microdeletions. Chromosomes were typed with a set of 11 binary Y markers, which identified 8 haplogroups in the sample. Haplogroup frequencies were compared between 3 microdeletion classes and the non-deleted infertile males. Deletions arise on many different haplotypic backgrounds. No statistically significant differences in frequency were seen, although the small number of AZFa deletions lay predominantly on one branch of the Y haplotype tree.

Genetic Defects of Male Infertility and ICSI

Intracytoplasmic sperm injection (ICSI) has caused a revolution in the treatment of severe male infertility. The direct injection of a single spermatozoon into the oocyte enables pregnancies in couples of whom the man has severe oligozoospermia or even azoospermia. This therapeutic revolution has unfortunately not been accompanied by a revolution in the knowledge of the etiology of the underlying problem. There are indications that genetic factors play a major role, and this may have serious consequences for the offspring.

Screening Male Intracytoplasmic Sperm Injection Candidates for Mutations of the Follicle Stimulating Hormone Receptor Gene

Follicle stimulating hormone (FSH) is considered to be essential for spermatogenesis. Therefore, genetic abnormalities of FSH signalling on testicular Sertoli cells would be expected to affect sperm production negatively in males. Inactivating FSH receptor mutations have been reported earlier in both males and females. All affected males had elevated FSH serum concentrations and abnormal sperm parameters. We postulated that inactivating FSH receptor mutations might be a cause of oligozoospermia or azoospermia and reviewed the clinical data of 151 male intracytoplasmic sperm injection (ICSI) candidates with special attention to FSH serum concentrations. The exclusion criteria for mutation screening of the FSH receptor gene were: a history of operative sterilization or testicular malignancy, congenital abnormality other than cryptorchidism, and a chromosomal aberration or a Y-chromosome microdeletion. The inclusion criteria were: male (ICSI candidate) with azoospermia or oligoasthenoteratozoospermia (OAT) and elevated FSH serum concentrations. In total, 23 males with OAT and five males with azoospermia were tested for mutations of the coding sequences and the intron-exon boundaries of the FSH receptor gene by polymerase chain reaction (PCR) followed by single strand conformation polymorphism analysis (SSCP). Neutral polymorphisms were readily detected using this technique in both probands and controls. None of the 28 selected patients showed a pathogenic FSH receptor mutation. Mutations in the FSH receptor gene are not a common cause of infertility in ICSI candidates.