11 research outputs found
X chromosome-linked CNVs in male infertility: discovery of overall duplication load and recurrent, patient-specific gains with potential clinical relevance.
Y-chromosome microdeletions are not associated with SHOX haploinsufficiency
studyquestion: Are Y-chromosome microdeletions associated with SHOX haploinsufficiency, thus representing a risk of skeletal anomalies
for the carriers and their male descendents?
summary answer: The present study shows that SHOX haploinsufficiency is unlikely to be associated with Y-chromosome microdeletions.
what is known already: Y-chromosome microdeletions are not commonly known as a major molecular genetic cause of any pathological
condition except spermatogenic failure. However, it has been recently proposed that they are associated not only with infertility but also
with anomalies in the pseudoautosomal regions (PAR), among which SHOX haploinsufficiency stands out with a frequency of 5.4% in microdeletion
carriers bearing a normal karyotype. This finding implies that sons fathered by men with Y-chromosome defects will not only exhibit fertility
problems, but might also suffer from SHOX-related conditions.
study design: Five European laboratories (Florence, Mu¨nster, Barcelona, Padova and Ancona), routinely performing Y-chromosome
microdeletion screening, were enrolled in a multicenter study.
participants/materials, setting, methods: PAR-linked and SHOX copy number variations (CNVs) were analyzed in 224
patients carrying Y-chromosome microdeletions and 112 controls with an intact Y chromosome, using customized X-chromosome-specific
array-CGH platforms and/or qPCR assays for SHOX and SRY genes.
main results and the role of chance: Our data show that 220 out of 224 (98.2%) microdeletion carriers had a normal SHOX
copy number, as did all the controls. No SHOX deletionswere found in any of the examined subjects (patients as well as controls), thus excluding
an association with SHOX haploinsufficiency. SHOX duplications were detected in 1.78% of patients (n ¼ 4), of whom two had an abnormal and
two a normal karyotype. This might suggest that Y-chromosome microdeletions have a higher incidence forSHOXduplications, irrespective of the
patient’s karyotype. However, the only clinical condition observed in our four SHOX-duplicated patients was infertility.
limitations, reasons for caution: The number of controls analyzed is rather low to assess whether the SHOX duplications
found in the two men with Y-chromosome microdeletions and a normal karyotype represent a neutral polymorphism or are actually associated
with the presence of the microdeletion.
wider implications of the findings: Men suffering from infertility due to the presence of Y-chromosome microdeletions can
resort to artificial reproductive technology (ART) to father their biological children. However, infertile couples must be aware of the risks implied
and this makes genetic counseling a crucial step in the patient’s management. This study does not confirm previous alarming data that showed an
association between Y-chromosome microdeletions and SHOX haploinsufficiency. Our results imply that deletion carriers have no augmented risk of SHOX-related pathologies (short stature and skeletal anomalies) and indicate that there is no need for radical changes in genetic counseling
of Yq microdeletion carriers attempting ART, since the only risk established so far for their male offspring remains impaired spermatogenesis
Clinical factors affecting semen improvement after microsurgical subinguinal varicocelectomy: Which subfertile patients benefit from surgery?
Comprehensive investigation in patients affected by sperm macrocephaly and globozoospermia
The aim of this study was to provide a comprehensive genetic/phenotypic characterization of subjects suffering infertility owing to sperm macrocephaly (n = 3) or globozoospermia (n = 9) and to investigate whether the patients' genetic status was correlated with the alteration of various sperm parameters. AURKC was sequenced in case of sperm macrocephaly while the DPY19L2 status has been analyzed by multiple approaches including a novel qPCR-based copy number assay in case of globozoospermia. Globozoospermic patients were also analyzed for SPACA1, a novel candidate gene herein tested for the first time in humans. The effect of the patients' genetic status was interrogated by implementing the molecular screening with the characterization of several sperm parameters: (i) routine sperm analysis, integrated with transmission electron microscopy; (ii) sperm fluorescent in situ hybridization (FISH) analysis; (iii) sperm DNA fragmentation (DF) analysis. Moreover, for the first time, we performed microsatellite instability analysis as a marker of genome instability in men with sperm macrocephaly and globozoospermia. Finally, artificial reproductive technology (ART) history has been reported for those patients who underwent the treatment. Macrocephalic patients had an AURKC mutation and >89% tetraploid, highly fragmented spermatozoa. DPY19L2 was mutated in all patients with >80% globozoospermia: the two homozygous deleted men and the compound heterozygous showed the severest phenotype (90-100%). The newly developed qPCR method was fully validated and has the potential of detecting also yet undiscovered deletions. DPY19L2 status is unlikely related to FISH anomalies and DF, although globozoospermic men showed a higher disomy rate and DF compared with internal reference values. No patient was mutated for SPACA1. Our data support the general agreement on the negative correlation between macro/globozoospermia and conventional intracytoplasmic sperm injection outcomes. Microsatellites were stable in all patients analyzed. The comprehensive picture provided on these severe phenotypes causing infertility is of relevance in the management of patients undergoing ART
Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men
Activation of adenosine A2A receptors suppresses the emission of pro-social and drug-stimulated 50-kHz ultrasonic vocalizations in rats: possible relevance to reward and motivation
Interactions between the endocannabinoid and nicotinic cholinergic systems: preclinical evidence and therapeutic perspectives
Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations
Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility