Aston K.I.,University of Utah |
Krausz C.,University of Florence |
Laface I.,University of Florence |
Ruiz-Castane E.,Andrology Service |
Carrell D.T.,University of Utah
Human Reproduction | Year: 2010
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. Result SSeveral 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. © The Author 2010.
Krausz C.,University of Florence |
Giachini C.,University of Florence |
Lo Giacco D.,Andrology Service |
Lo Giacco D.,Autonomous University of Barcelona |
And 6 more authors.
PLoS ONE | Year: 2012
Context: The role of CNVs in male infertility is poorly defined, and only those linked to the Y chromosome have been the object of extensive research. Although it has been predicted that the X chromosome is also enriched in spermatogenesis genes, no clinically relevant gene mutations have been identified so far. Objectives: In order to advance our understanding of the role of X-linked genetic factors in male infertility, we applied high resolution X chromosome specific array-CGH in 199 men with different sperm count followed by the analysis of selected, patient-specific deletions in large groups of cases and normozoospermic controls. Results: We identified 73 CNVs, among which 55 are novel, providing the largest collection of X-linked CNVs in relation to spermatogenesis. We found 12 patient-specific deletions with potential clinical implication. Cancer Testis Antigen gene family members were the most frequently affected genes, and represent new genetic targets in relationship with altered spermatogenesis. One of the most relevant findings of our study is the significantly higher global burden of deletions in patients compared to controls due to an excessive rate of deletions/person (0.57 versus 0.21, respectively; p = 8.785×10-6) and to a higher mean sequence loss/person (11.79 Kb and 8.13 Kb, respectively; p = 3.435×10-4). Conclusions: By the analysis of the X chromosome at the highest resolution available to date, in a large group of subjects with known sperm count we observed a deletion burden in relation to spermatogenic impairment and the lack of highly recurrent deletions on the X chromosome. We identified a number of potentially important patient-specific CNVs and candidate spermatogenesis genes, which represent novel targets for future investigations. © 2012 Krausz et al.
Terribas E.,Hospital Duran i Reynals |
Terribas E.,Institute Of Medicina Predictiva I Personalitzada Del Cancer Imppc |
Bonache S.,Hospital Duran i Reynals |
Garcia-Arevalo M.,Hospital Duran i Reynals |
And 5 more authors.
Journal of Andrology | Year: 2010
DNA mismatch repair (MMR) genes have been described to participate in crossover events during meiotic recombination, which is, in turn, a key step of spermatogenesis. This evidence suggests that MMR family gene expression may be altered in infertile men with defective sperm production. In order to determine the expression profile of MMR genes in impaired human spermatogenesis, we performed transcript levels analysis of MMR genes (MLH1, MLH3, PMS2, MSH4, and MSH5), and other meiosis-involved genes (ATR, HSPA2, and SYCP3) as controls, by real-time reverse transcription-polymerase chain reaction in testis from 13 patients with spermatogenic failure, 5 patients with primary germ cell tumors, and 10 controls with conserved spermatogenesis. Correlation of the expression values with the histological findings was also performed. The MMR gene expression values, with the exception of PMS2, are significantly decreased in men with spermatogenic failure. The pattern of MMR reduction correlates with the severity of damage, being maximum in maturation arrest. Specifically, expression of the testicular MSH4 gene could be useful as a surrogate marker for the presence of intratesticular elongated spermatid in patients with nonobstructive azoospermia, contributing to predict the viability of assisted reproduction. Interestingly, a reduction in the MSH4 and MSH5 transcript concentration per spermatocyte was also observed. The decreased expression level of other meiosis-specific genes, such as HSPA2 and SYCP3, suggests that the spermatocyte capacity to express meiosis-related genes is markedly reduced in spermatogenic failure, contributing to meiosis impairment and spermatogenic blockade. Copyright © American Society of Andrology.
Natali I.,Sterility Center |
Simi S.,Andrology Service |
Cipriani S.,Sterility Center |
Cipriani S.,University of Milan |
And 4 more authors.
Journal of Andrological Sciences | Year: 2010
Objective: Aim of this study was to evaluate the relation between Type A spermatozoa motility in ejaculate of treated infertile men and incidence of pregnancy achieved with artificial insemination. Materials and methods. 72 infertile males from couples with only male infertility, were included in the study. Seminal fluid was assayed according to the World Health Organization guidelines and semen was prepared through gradient density for insemination. Couples were followed to evaluate pregnancy occurrence. Four categories of Type A spermatozoa were identified: first = 0-10%, second = 11-30%, third = 31-50% and fourth = 51-100%. Data were analyzed using the logistic regression model to estimate the relative risk (RR). Results. Pregnancy rates in the four Type A spermatozoa categories were: 11.8% (SE = 7.8), 45.0% (SE = 11.1), 26.7% (SE = 11.4) and 30.0% (SE = 10.3). Using the first Type A spermatozoa category as reference, the second category was significantly different in pregnancy incidence (RR = 6.14, p-value = 0.0385), but no difference emerged in the third and fourth category (RR = 2.7, p-value = 0.2924 and RR = 3.2, p-value = 0.1931). Conclusions. This study shows that having Type A spermatozoa percentage lower than 10% is an unfavorable factor, whereas the highest number of pregnancies occurred with spermatozoa in the 11-30% category. Further percentage increase of Type A spermatozoa did not improve the pregnancy rate. Notwithstanding the little sample size, these data suggest that a significant relation exists between Type A spermatozoa in the ejaculate and pregnancy rate.