Seladin-1 and testicular germ cell tumours: new insights into cisplatin responsiveness.

The molecular basis for the exquisite sensitivity of testicular germ cell tumours of adolescents and adults (TGCTs), ie seminomas and non-seminomatous germ cell tumours, to chemo/radiotherapy has not been fully clarified so far. It has been suggested that it may be dependent on factors involved in the regulation of apoptosis. Seladin-1 is a multi-functional protein involved in various biological processes, including apoptosis. The aim of our study was to assess the expression of seladin-1 in different histological types of TGCTs, known to have varying treatment sensitivity, in order to establish whether this protein may influence cisplatin responsiveness in vitro. Seladin-1 expression levels, both at the mRNA and at the protein level, were higher in the adjacent normal parenchyma than in the pathological counterparts. In tumoural tissues, the level of expression differed among TGCT histological types. The highest tumour-expression level was found in teratoma, whereas the lowest was detected in seminoma, corresponding to the different chemo/and radiosensitivities of these tumour types. In common with other cancers, in TGCT-derived cell lines seladin-1 showed anti-apoptotic properties through inhibition of caspase-3 activation. We confirmed our results using a non-seminomatous cell line model (NT2) before and after differentiation with retinoic acid. Significantly higher seladin-1 expression was observed in the differentiated derivatives (teratoma) and an inverse relationship was found between seladin-1 expression and the amount of cleaved caspase-3. Seladin-1 silencing or overexpression in this cell line supports involvement of seladin-1 in cisplatin responsiveness. Seladin-1 silencing was associated with greater cisplatin responsiveness demonstrated by decreased cell viability and increased expression of apoptotic markers. In contrast, overexpression of seladin-1 was associated with a higher survival rate and a clear anti-apoptotic effect. In conclusion, we have demonstrated for the first time an important role for seladin-1 in the biology of TGCTs and provided new insights into cisplatin responsiveness of these tumours.

The leucine-rich repeat-containing G protein-coupled receptor 8 gene T222P mutation does not cause cryptorchidism.

CONTEXT: Insulin-like 3 and its receptor, leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8), are essential for the first phase of testicular descent. Homozygous loss of either of the two genes in mice leads to cryptorchidism. Although mutations in both homologous human genes are not a common cause of cryptorchidism. To date, only one missense mutation at codon 222 (T222P) of the LGR8 gene has been proposed as a causative mutation for cryptorchidism. This conclusion was based on both functional in vitro studies and the lack of mutation in a large group of controls. The geographical origin of the mutation carriers suggested a founder effect in the Mediterranean area. OBJECTIVES: We sought to define the frequency of the T222P mutation in four different countries to assess whether the screening for this mutation could be of use as a diagnostic genetic test. MATERIALS AND METHODS: A total of 822 subjects (359 with a history of cryptorchidism and 463 controls) from Italy, Spain, Hungary, and Egypt were genotyped for the T222P mutation by direct sequencing. RESULTS: The phenotypical expression of the mutation also included normal testicular descent. The mutation frequency was not significantly different in cryptorchid patients vs. noncryptorchid controls (3.6 vs. 1.7%, respectively). No significant geographical differences were observed in mutation frequencies. The haplotype analysis allowed us to predict three distinct haplotypes, i.e. three possible mutation events. CONCLUSIONS: Our results suggest that the T222P mutation cannot be considered either causative or a susceptibility factor for cryptorchidism. A true causative mutation in the LGR8 gene still remains to be identified.

[Conservative treatment of erectile dysfunction]. / Merevedési zavarok konzervatív kezelése.

The development of diagnostical and therapeutical methods of erectile dysfunction opened new possibilities for patients. In our time, andrologists are capable of treating most patients. The ones who cannot be helped are unable to lead sexual life due to physical reasons. The application of hormone examinations, color Doppler and Rigiscan exams help at establishing diagnoses. In the therapy, modern peroral pharmacotherapy is dominant, mainly phosphodiesterase inhibitors and central peroral pharmacon are applied. The means of getting the vasoactive drugs into the body have been extended (subcutan, transdermal, and drugs absorbable through mucosa). Psychotherapy is indispensable at some patients. The surgical solution (mainly prosthesis implantation) can be regarded critically, yet their presence among therapies is necessary. According to authors' opinion, the qualitative development of vasoactive drugs (efficacy extension and side-effect reduction) that can be simply and conveniently applied in the future.

Segregation of chromosomes in spermatozoa of four Hungarian translocation carriers.

OBJECTIVE: To determine the segregation pattern of the translocated chromosomes in spermatozoa of human males with translocations. DESIGN: Retrospective case-control study. SETTING: Hospital-based genetic laboratory for reproductive biology. PATIENT(S): A carrier with Y-autosome reciprocal translocation, two with autosome-autosome reciprocal translocations, and one with Robertsonian translocation. INTERVENTION(S): Blood sample and sperm sample collection from each translocation carrier. MAIN OUTCOME MEASURE(S): Fluorescence in situ hybridization on lymphocyte slides to characterize each translocation case. Fluorescence in situ hybridization with specific DNA probes for each of the sperm samples to characterize the chromosomes involved in the rearrangement and to evaluate the possible interchromosomal effect for chromosomes 18, X, and Y. RESULT(S): Each translocation carrier showed a specific mode of segregation pattern of the translocated chromosomes, confirming the dependence on chromosomes involved in the translocation. The highest frequency from alternate segregation was with the carrier of Robertsonian translocation (90.9%), and the lowest was with the carrier of Y-autosome translocation (29.7%). No evidence of an interchromosomal effect for chromosomes 18, X, and Y were detected. CONCLUSION(S): Depending on the rate of the genetically normal and abnormal segregation modes, we can evaluate the chance of having a healthy proband. These results ensure more accurate genetic counseling for patients in assisted reproduction centers.

Meiotic studies of infertile men in case of non-obstructive azoospermia with normal karyotype and no microdeleted Y-chromosome precise the clinical couple management.

To identify meiotic criteria for infertility management in non-obstructive azoospermic men, a prospective and multicentric study was organized in Andrological Departments of Paris (France), Roma (Italy) and Budapest (Hungary). In 117 non-obstructive azoospermic men with normal karyotype and no Y-chromosome microdeletion, histology and meiotic studies on bilateral bipolar testicular biopsies were done. Histologically, 40 patients (34%) presented spermatocyte or spermatid arrest, 39 (33%) hypospermatogenesis whereas no meiotic cell could be observed in the remaining patients (33%). Cytogenetically, meiotic figures could only be obtained from the two first histological groups. Meiotic abnormalities were observed in a total of 44 patients (37.6%) including nine patients (7.7%) with severe class I and class IIB anomalies and 19 patients (16.2%) with class IIC environmentally linked meiotic abnormalities. These results provided essential clues for an accurate clinical management. For patients with no meiotic figures and patients with class I and class IIB anomalies, an hormonal stimulation is illusory and a sperm gift should be directly proposed. An hormonal stimulation should be proposed to all the other patients, either directly or following the treatment of the testicular microenvironment for the patients presenting class IIC anomalies. The genetic risk and possibility of prenatal chromosomal analysis in case of pregnancy should be clearly exposed to all the couples in all the cases where type IIA, III or IV anomalies are present. This therapeutical strategy has been applied to all the patients in our series.