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Biomedical subjects

C Foresta

Publications and source records attributed to C Foresta.

149 records · Page 9Linked to original sources

[Analysis of sperm aneuploidy in infertile subjects after chemotherapy treatment].

The continuing search for a cure for cancer has developed more aggressive therapies that may damage germ cells, leading to clinical disease in offspring of survivors. Standard therapy for the majority of cancer today consists in combinations of high doses of radiation and chemotherapy drugs. We investigated the effect of cancer treatments on the reproductive potential of men. Multicolor fluorescence in situ hybridization has been used to recognize chromosomes X, Y and 8 in sperm of 10 severely oligozoospermic subjects (sperm concentration < 5,000,000/mL) treated for cancer at least 5 years before the beginning of this study. As controls, we analyzed sperm aneuploidies in 20 fertile men (sperm concentration > 20,000,000/mL) and in 20 severe idiopathic oligozoospermic subjects (sperm concentration < 5,000,000/mL). In all subjects, X- and Y-bearing spermatozoa were present in a normal 1:1 ratio; nevertheless the frequency of 24,XY, 24,XX and 24,YY disomic sperm was significantly higher in patients treated for cancer and in idiopathic oligozoospermic subjects with respect to normozoospermic men. These results suggest that the increase in sperm aneuploidies in treated patients cannot be reported directly to precedent chemotherapy, but reflects the alteration of testicular structure, as in the case of severe idiopathic oligozoospermic subjects. With the advent of intra-cytoplasmic sperm injection, it is possible to offer the opportunity to conceive in men affected by severe oligozoospermia but it is also possible, when the spermatozoa of these subjects are used, to pass sex chromosome abnormalities on to the children. We therefore suggest caution before application of an artificial reproductive technique in severe oligozoospermic patients.

Analysis of Variance↗

[Microdeletion of chromosome Y in male infertility: role of the DAZ gene].

Microdeletions of the Y chromosome represent the most frequent cause of male infertility, being responsible for 10-15% of cases of azoospermia or severe oligozoospermia. Such mutations localize in one or more loci named azoospermia factor (AZF) a, b and c. Mutations more frequently involve the DAZ gene in AZFc, and could determine both azoospermia and severe oligozoospermia. It is therefore difficult to find a clear relationship between genotype and phenotype. DAZ is present in multiple copies in AZFc, and this causes the gene to be difficult to analyze. In fact, polymerase chain reaction, the principal technique utilized for detection of the deletions, cannot distinguish among the different copies of the gene. Furthermore, it is not clear if all the DAZ copies are expressed in the testis, and other genes, such as CDY1, map in AZFc; therefore their alteration may play a role in determining the phenotype. In this review we report the current knowledge on the function of the Y chromosome in human spermatogenesis. In particular we analyze some of our experimental studies on the role of the DAZ gene family. Expression studies allowed us to clarify that an altered expression of DAZ might cause infertility in patients with severe testiculopathies. Furthermore, we describe for the first time a deletion not involving all the DAZ copies in a patient with severe hypospermatogenesis and we clarify that CDY1 is not involved in the testicular damage observed in patients with deletions of DAZ. These studies elucidate the role of DAZ and have important clinical consequences in the diagnostic and therapeutic approach of the infertile patient, above all when he is a candidate for assisted reproduction techniques, due to the possibility of transmitting the genetic alteration to the offspring.

Chromosome Deletion↗

Possible significance of seminal zinc on human spermatozoa functions.

This study has been performed to investigate the possible role of seminal zinc in the regulation of human spermatozoa functions. Sperm cells from fertile men were washed and pooled, and in each cellular suspension we determined: a) spermatozoal uptake of zinc, b) effects of different albumin concentrations on cellular zinc content, c) effects of zinc and albumin on spermatozoal O2 consumption, d) effects of different zinc concentrations on albumin induced acrosome reaction. We observed that increases of extracellular zinc cause corresponding increases of spermatozoal zinc and that albumin exerts an important chelating effect, even at very low concentrations, on cellular zinc content. Zinc also possesses a reversible inhibitory effect on spermatozoa O2 consumption in a dose-related way, and albumin is able to reverse this effect. Albumin-induced acrosome reaction was also significantly reduced by addition of different zinc concentrations. Our findings reveal that zinc exerts an important influence on human spermatozoa functions and suggest that zinc may be involved in the mechanisms that maintain spermatozoa in the transitory quiescent state until penetration in the female reproductive tract.

Acrosome↗

Sperm nuclear chromatin heterogeneity in infertile subjects.

Sperm chromatin heterogeneity has been evaluated in infertile males affected by different testicular diseases: 37 subjects had undergone orchidopexy in childhood (ex-cryptorchid), 50 were affected by idiopathic varicocele, 18 had a history of bilateral post-parotitis orchitis and 23 were "idiopathic infertiles". All subjects, except post-parotitis orchitic patients, exhibited significantly higher sperm chromatin heterogeneity than controls, with the highest incidence in ex-cryptorchid and in idiopathic infertiles. Ex-cryptorchid subjects also presented a significant positive linear correlation (p less than 0.001) between degree of sperm chromatin abnormality and percentage of morphological sperm alterations. Four monolateral ex-cryptorchid subjects showed a higher percentage of chromatin heterogeneity even when the cryptorchid testis had been removed during orchidopexy. In patients affected by varicocele, we also observed a significant correlation between chronological age and percentage of chromatin alterations. The results are discussed in relation to the pathogenesis of the disease concerned. Since sperm chromatin heterogeneity appears to be strongly involved in the development of infertility, we would suggest that it should be evaluated in routine diagnostic procedures of male infertility.

Adult↗