Showing papers by "Csilla Krausz published in 2010"

Evaluation of 172 candidate polymorphisms for association with oligozoospermia or azoospermia in a large cohort of men of European descent

Abstract: BACKGROUND In spite of tremendous efforts by a number of groups, the search for single nucleotide polymorphisms (SNPs) strongly associated with male factor infertility by means of gene re-sequencing studies has yielded few likely candidates. A recent pilot, genome-wide SNP association study (GWAS) identified a list of SNPs associated with oligozoospermia and azoospermia. This is an expanded follow-up study of the SNPs identified by the GWAS as well as other SNPs from previously published gene re-sequencing studies. METHODS On the basis of the pilot GWAS and SNPs with published associations with male infertility, 172 SNPs were genotyped in men with idiopathic azoospermia or oligozoospermia using the Illumina BeadXpress platform. RESULTS Several SNPs were identified or confirmed to be significantly associated with oligozoospermia and/or azoospermia. More importantly, this follow-up study indicates that, at least in Caucasian men, no single common SNP accounts for a significant proportion of spermatogenic failure cases. CONCLUSIONS The associations reported in this study are promising, but much larger genome-wide studies will be necessary to confidently validate these SNPs and identify novel SNPs associated with male infertility.

Klinefelter’s Syndrome: A Clinical and Therapeutical Update

Abstract: The prevalence of the Klinefelter's syndrome, ranging between 1/500 and 1/1,000 in the general male population, rises up to 3-4% among infertile males and to 10-12% in azoospermic patients. Due to the paucity of symptoms, only 10% of Klinefelter patients are diagnosed prepubertally. The clinical spectrum of the phenotype of adult Klinefelter patients is very broad and ranges from clinically overt hypogonadism to normally virilized males. The diagnosis is usually made during the evaluation of couple infertility. The only nearly constant clinical feature is the reduced testicular volume and azoospermia or, in few cases, cryptozoospermia. Due to the variability of the phenotype and also to the fact that the main symptoms of the syndrome (androgen deficiency, infertility) are in the reproductive domain, approximately two thirds of Klinefelter patients are not diagnosed during their life. Low/normal testosterone and high levels of the luteinizing hormone (LH) suggest that all Klinefelter patients have overt or compensated hypogonadism which should be treated with testosterone, starting from the peri-pubertal age. Even if no medical treatment is possible for infertility, testicular sperm for assisted reproduction techniques can be obtained by multiple testicular biopsies in experienced centers in up to 50% of subjects. Although there are no predictors for successful sperm retrieval, the birth of 101 children with normal karyotype was reported in the last 15 years. Furthermore, the genetic risk to the offspring of Klinefelter patients has recently not been found to be greater than that of patients with nonobstructive azoospermia with normal karyotype.

Small variations in crucial steps of TUNEL assay coupled to flow cytometry greatly affect measures of sperm DNA fragmentation.

Abstract: Techniques for assessing sperm DNA damage are numerous and various There are 2 main types of assay: direct and indirect The former directly detects the amount of sperm DNA damage, whereas the latter reveals the effects of an exogenous insult on sperm chromatin In addition, even considering the same type of technique, different strategies to reveal or quantify sperm DNA damage, or both, are used Finally, these techniques, except for sperm chromatin structure assay (SCSA), lack standardized protocols to which all users can adhere to minimize interlaboratory variations In this study, we investigated the effects of some of the many ways the terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling (TUNEL) assay is performed when measuring sperm DNA fragmentation by flow cytometry In addition, by using an established procedure, we determined the precision of the technique by calculating intra-assay coefficients of variation (CVs) We found that concentration of the fixative, the time of storage of fixed samples, the fluorochrome used to label DNA breaks, and the method used to analyze flow cytometric data all greatly affect the measures of sperm DNA fragmentation In particular, we found that treatment with paraformaldehyde produced additional damage in most samples, suggesting that TUNEL also can be considered an indirect assay when performed in semen samples treated with such a fixative reagent We also showed that 2 different methods used to analyze data yielded results that, albeit correlating, were different and associated differently to semen quality On the contrary, the TUNEL assay, as measured here, showed low intraassay CVs, resulting in a quite precise technique when performed in established conditions

TSPY and Male Fertility.

Abstract: Spermatogenesis requires the concerted action of thousands of genes, all contributing to its efficiency to a different extent. The Y chromosome contains several testis-specific genes and among them the AZF region genes on the Yq and the TSPY1 array on the Yp are the most relevant candidates for spermatogenic function. TSPY1 was originally described as the putative gene for the gonadoblastoma locus on the Y (GBY) chromosome. Besides its oncogenic properties, expression analyses in the testis and in vitro and in vivo studies all converge on a physiological involvement of the TSPY1 protein in spermatogenesis as a pro-proliferative factor. The majority of TSPY1 copies are arranged in 20.4 kb of tandemly repeated units, with different copy numbers among individuals. Our recent study addressing the role of TSPY1 copy number variation in spermatogenesis reported that TSPY1 copy number influences spermatogenic efficiency and is positively correlated with sperm count. This finding provides further evidence for a role of TSPY1 in testicular germ cell proliferation and stimulates future research aimed at evaluating the relationship between the copy number and the protein expression level of the TSPY1 gene.

Genetic testing of male infertility

Abstract: Patients with severe male factor are more likely to be carriers of chromosomal abnormalities both in their sperm and in their lymphocytes. These abnormalities include numerical alterations, structural alterations, and Y chromosome microdeletions. Gene mutations that cause male infertility and studies identifying polymorphic regions that, in conjunction with environmental factors, may be associated with male infertility have been described. Until further gene mutations are identified, standard genetic testing of infertile men is largely limited to chromosomal karyotyping, Y chromosome analysis, and cystic fibrosis gene mutation analysis.