Analysis of copy number variation in men with non-obstructive azoospermia
Wyrwoll MJ, Wabschke R, Röpke A, Wöste M, Ruckert C, Perrey S, Rotte N, Hardy J, Astica L, Lupiáñez DG, Wistuba J, Westernströer B, Schlatt S, Berman AJ, Müller AM, Kliesch S, Yatsenko AN, Tüttelmann F, Friedrich C., 30.08.2022
Abstract
Background: Recent findings demonstrate that single nucleotide variants can cause non-obstructive azoospermia (NOA). In contrast, copy number variants (CNVs) were only analysed in few studies in infertile men. Some have reported a higher prevalence of CNVs in infertile versus fertile men. Objectives: This study aimed to elucidate if CNVs are associated with NOA. Materials and methods: We performed array-based comparative genomic hybridisation (aCGH) in 37 men with meiotic arrest, 194 men with Sertoli cell-only phenotype, and 21 control men. We filtered our data for deletions affecting genes and prioritised the affected genes according to the literature search. Prevalence of CNVs was compared between all groups. Exome data of 2,030 men were screened to detect further genetic variants in prioritised genes. Modelling was performed for the protein encoded by the novel candidate gene TEKT5 and we stained for TEKT5 in human testicular tissue. Results: We determined the cause of infertility in two individuals with homozygous deletions of SYCE1 and in one individual with a heterozygous deletion of SYCE1 combined with a likely pathogenic missense variant on the second allele. We detected heterozygous deletions affecting MLH3, EIF2B2, SLX4, CLPP and TEKT5, in one subject each. CNVs were not detected more frequently in infertile men compared with controls. Discussion: While SYCE1 and MLH3 encode known meiosis-specific proteins, much less is known about the proteins encoded by the other identified candidate genes, warranting further analyses. We were able to identify the cause of infertility in one out of the 231 infertile men by aCGH and in two men by using exome sequencing data. Conclusion: As aCGH and exome sequencing are both expensive methods, combining both in a clinical routine is not an effective strategy. Instead, using CNV calling from exome data has recently become more precise, potentially making aCGH dispensable.
Wyrwoll MJ, Wabschke R, Röpke A, Wöste M, Ruckert C, Perrey S, Rotte N, Hardy J, Astica L, Lupiáñez DG, Wistuba J, Westernströer B, Schlatt S, Berman AJ, Müller AM, Kliesch S, Yatsenko AN, Tüttelmann F, Friedrich C. Analysis of copy number variation in men with non-obstructive azoospermia. Andrology. 2022 Nov;10(8):1593-1604. doi: 10.1111/andr.13267. Epub 2022 Sep 23.
Publication: https://onlinelibrary.wiley.com/doi/10.1111/andr.13267
Disclaimer
The publication Analysis of copy number variation in men with non-obstructive azoospermia by Wyrwoll MJ, Wabschke R, Röpke A, Wöste M, Ruckert C, Perrey S, Rotte N, Hardy J, Astica L, Lupiáñez DG, Wistuba J, Westernströer B, Schlatt S, Berman AJ, Müller AM, Kliesch S, Yatsenko AN, Tüttelmann F, Friedrich C. is published under an open access license: https://creativecommons.org/licenses/by-nc/4.0/. Permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Curation by the MFGA team Relevant data sets presented in the publication have been identified. If possible, annotations (title, general information, conditions, processed tissue types and processed cell types) have been added based on information from the publication. Data tables and images that provide a good overview on the publication's findings on the data set have been extracted from the publication and/or supplement. If not stated otherwise, images are depicted with title and description exactly as in the publication. Tables have been adjusted to the MFGA table format. Conducted adjustments are explained in the detailed view of the tables. However, titles and descriptions have been adopted from the publication.
Data set 1: Analysis of copy number variation in men with non-obstructive azoospermia
Exome: Whole Exome Sequencing
Species
| Species |
|---|
| Human |
Tissue Types
| BRENDA tissue ontology | Maturity | Description | Species | Replicates |
|---|---|---|---|---|
| BTO_0001363: testis | Adult | A typically paired male reproductive gland that produces sperm and that in most mammals is contained within the scrotum at sexual maturity. | Human |
Cell Types
| Cell ontology | Maturity | Description | Species | Replicates | Cells per replicate |
|---|---|---|---|---|---|
| CL_0000216: Sertoli cell | A supporting cell projecting inward from the basement membrane of seminiferous tubules. They surround and nourish the developing male germ cells and secrete androgen binding protein. Their tight junctions with the spermatogonia and spermatocytes provide a blood-testis barrier. | Human |
Data set 2: Immunohistochemistry of TEKT5 in fetal and adult human and mouse testes
Exome: Array-based comparative genomic hybridisation
Tissue Types
| BRENDA tissue ontology | Maturity | Description | Species | Replicates |
|---|---|---|---|---|
| BTO_0001363: testis | Fetal and Adult | A typically paired male reproductive gland that produces sperm and that in most mammals is contained within the scrotum at sexual maturity. | Human and Mouse |
Images
Figure 1: Histological analysis of the TEKT5 protein expression by immunohistochemical staining
(A, B) Testis tissue from fetal mouse and human biopsies was stained with TEKT5 primary antibody (PA5-21157), resulting in a germ cell-specific staining pattern. (C, D) Evaluation of adult murine and human tissue confirmed characteristic protein expression of the germ cell population, mainly including spermatocytes and round and elongated spermatids. (E) Isotype-specific immunoglobin (IgG) was used as a technical control. (F) Man M877, displaying a Sertoli cell-only phenotype (SCO), showed no specific TEKT5 staining since germ cells were absent within the testicular tubules. Scale bars are indicated in each micrograph
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