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UBE2B mRNA alterations are associated with severe oligozoospermia in infertile men.
MedLine Citation:
PMID:  23378580     Owner:  NLM     Status:  Publisher    
Oligozoospermia (low sperm count) is a common semen deficiency. However, to date, few genetic defects have been identified to cause this condition. Moreover, even fewer molecular-genetic diagnostic tests are available for patients with oligozoospermia in the andrology clinic. Based on animal and gene expression studies of oligozoospermia, several molecular pathways may be disrupted in post-meiotic spermatozoa. One of the disrupted pathways is protein ubiquitination and cell apoptosis. A critical protein involved in this pathway is the ubiquitin conjugating enzyme 2B, UBE2B. Absence of Ube2b in male mice causes spermatogenic meiotic disruption with increased apoptosis, leading to infertility. To examine the association between messenger RNA defects in UBE2B and severe oligozoospermia (0.1-10x10(6) cells/ml), sequencing screening of sperm cDNA in 326 oligozoospermic patients and 421 normozoospermic men was performed. mRNA alterations in UBE2B were identified in sperm in 4.6% (15/326) of the oligozoospermic patients, but not found in control men, suggesting strong association between mRNA defects and oligozoospermia (χ(2)=19, p=0.0001). Identified UBE2B alterations include 9 splicing, 4 missense, and 2 nonsense alterations. The following screen of corresponding DNA regions did not reveal causative DNA mutations, suggesting a post-transcriptional nature of identified defects. None of these variants were reported in the dbSNP database, although other splicing abnormalities with low level of expression were present in 11/421 (2.6%) controls. Our findings suggest that two distinct molecular mechanisms, mRNA editing and splicing processing, are disrupted in oligozoospermia. We speculate that the contribution of post-transcriptional mRNA defects to oligozoospermia could be greater than previously anticipated.
Alexander N Yatsenko; Andrew P Georgiadis; Lata J Murthy; Dolores J Lamb; Martin M Matzuk
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-31
Journal Detail:
Title:  Molecular human reproduction     Volume:  -     ISSN:  1460-2407     ISO Abbreviation:  Mol. Hum. Reprod.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-2-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9513710     Medline TA:  Mol Hum Reprod     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of OBGYN, School of Medicine, University of Pittsburgh.
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