Document Detail

AZFa protein DDX3Y is differentially expressed in human male germ cells during development and in testicular tumours: new evidence for phenotypic plasticity of germ cells.
MedLine Citation:
PMID:  22466863     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: DDX3Y (DBY), located within AZoospermia Factor a (AZFa) region of the human Y chromosome (Yq11), encodes a conserved DEAD-box RNA helicase expressed only in germ cells and with a putative function at G1-S phase of the cell cycle. Deletion of AZFa results most often in germ cell aplasia, i.e. Sertoli-cell-only syndrome. To investigate the function of DDX3Y during human spermatogenesis, we examined its expression during development and maturation of the testis and in several types of testicular germ cell tumours (TGCTs), including the pre-invasive carcinoma in situ (CIS) precursor cells which are believed to originate from fetal gonocytes.
METHODS: DDX3Y protein expression was analysed during development in different tissues by western blotting. The localization of DDX3Y in normal fetal and prepubertal testis tissue of different ages as well as in a series of distinct TGCT tissue samples (CIS, classical seminoma, spermatocytic seminoma, teratoma and embryonal carcinoma) was performed by immunohistochemistry.
RESULTS: Germ cell-specific expression of DDX3Y protein was revealed in fetal prospermatogonia but not in gonocytes and not before the 17th gestational week. After birth, DDX3Y was expressed at first only in the nuclei of Ap spermatogonia, then also in the cytoplasm similarly to that seen after puberty. In CIS cells, DDX3Y was highly expressed and located predominantly in the nuclei. In invasive TGCT, significant DDX3Y expression was found in seminomas of the classical and spermatocytic type, but not in somatically differentiated non-seminomas, consistent with its germ-cell specific function.
CONCLUSIONS: The fetal germ cell DDX3Y expression suggests a role in early spermatogonial proliferation and implies that, in men with AZFa deletion, germ cell depletion may begin prenatally. The strong expression of DDX3Y in CIS cells, but not in gonocytes, indicates phenotypic plasticity of CIS cells and suggests partial maturation to spermatogonia, likely due to their postpubertal microenvironment.
B Gueler; S B Sonne; J Zimmer; B Hilscher; W Hilscher; N Græm; E Rajpert-De Meyts; P H Vogt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-30
Journal Detail:
Title:  Human reproduction (Oxford, England)     Volume:  27     ISSN:  1460-2350     ISO Abbreviation:  Hum. Reprod.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-22     Completed Date:  2012-09-17     Revised Date:  2013-02-26    
Medline Journal Info:
Nlm Unique ID:  8701199     Medline TA:  Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  1547-55     Citation Subset:  IM    
Department of Gynaecological Endocrinology and Reproductive Medicine, University of Heidelberg, Heidelberg, Germany.
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MeSH Terms
Azoospermia / genetics
Blotting, Western
Carcinoma in Situ / genetics
Chromosomes, Human, Y
DEAD-box RNA Helicases / analysis,  genetics*,  physiology*
Gene Deletion
Gene Expression*
Gestational Age
Neoplasms, Germ Cell and Embryonal / genetics
Seminoma / genetics
Spermatogonia / cytology,  metabolism
Spermatozoa / metabolism*
Teratoma / genetics
Testicular Neoplasms / genetics*
Testis / chemistry,  embryology,  growth & development*
Reg. No./Substance:
EC 3.6.1.-/DDX3Y protein, human; EC 3.6.1.-/DEAD-box RNA Helicases
Comment In:
J Urol. 2013 Feb;189(2):655-6   [PMID:  23312195 ]

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