Vyacheslav B Chernykh, Elizaveta E Bragina, Lyubov F Kurilo, Maria A Pankratenkova, Anna A Kashintsova, Mikhail Yu Gabliya, Igor V Vinogradov, Irina I Vityazeva, Sergey V Bogolyubov, Victor E Spangenberg, Oxana L Kolomiets
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引用次数: 0
Abstract
Background: The Y chromosome microdeletions are common genetic cause of male infertility. Mechanisms of impaired spermatogenesis and meiosis, as well as phenotypic variability, have not been sufficiently studied.
Objective: The paper provides results of the spermatogenesis and meiotic study based on the analysis of synaptonemal complex (SC) in the spermatocyte nuclei in infertile men with Y chromosome microdeletions.
Materials and methods: Examined cohort consisted of 9 male patients 27-32 years old with primary infertility with non-obstructive azoospermia. The patients had a 46,XY karyotype, complete (n = 4) and partial AZFc (n = 2) deletions, and complete AZFb (n = 2) and AZFb+c (n = 1) deletions. Semen analysis was performed and assessed according to the WHO guidelines (WHO, 2010). The AZF deletions were detected by multiplex PCR, analyzing Y-specific loci in accordance with the guidelines for molecular diagnosis of the Y chromosome microdeletions. Testicular biopsy was performed by with the TESE technique. Testicular tissue fragments were assessed under a light microscope for the presence of spermatocytes, spermatids, spermatozoa, atypical and degenerating germ cells in the suspension and analyzed by histopathology. Immunostaining was performed using antibodies to the SYCP3, γH2AFX, RAD51, and MLH1 proteins.
Results: In 6 examined patients, spermatocytes were found at following stages of the prophase I of meiosis: leptotene - 32.3 ± 39.4 (0-100)%, zygotene - 17.4 ± 20.1 (0-63.6)%, pachytene - 48.6 ± 38.2 (0-100)%, diplotene - 1.8 ± 2.2 (0-5.6)%. Percentage of germ cells at these stages was very close between patients with AZFb, AZFb+c, and AZFc deletions. Meiotic arrest at the zygotene stage with atypical SCs and incomplete synapsis in all nuclei was found in patient with complete AZFb+c deletion. Complete meiotic arrest at early-mid-pachytene was characterized for complete AZFc and AZFb deletions. Azoospermic patients with partial AZFc (gr/gr) deletions had incomplete meiotic arrest at the mid-pachytene stage.
Conclusion: Our own and literature data indicate more severe spermatogenesis and meiosis failures in patients with AZFb+c and AZFb deletions in comparison with AZFc deletions. Meiotic arrest at early-mid-pachytene was common, but some variability was found in the severity of spermatogenesis abnormalities in patients with complete AZFc deletions that requires further research.
期刊介绍:
During the last decades, ''Cytogenetic and Genome Research'' has been the leading forum for original reports and reviews in human and animal cytogenetics, including molecular, clinical and comparative cytogenetics. In recent years, most of its papers have centered on genome research, including gene cloning and sequencing, gene mapping, gene regulation and expression, cancer genetics, comparative genetics, gene linkage and related areas. The journal also publishes key papers on chromosome aberrations in somatic, meiotic and malignant cells. Its scope has expanded to include studies on invertebrate and plant cytogenetics and genomics. Also featured are the vast majority of the reports of the International Workshops on Human Chromosome Mapping, the reports of international human and animal chromosome nomenclature committees, and proceedings of the American and European cytogenetic conferences and other events. In addition to regular issues, the journal has been publishing since 2002 a series of topical issues on a broad variety of themes from cytogenetic and genome research.