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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

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  1. Age-related changes in human Leydig cell status

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  2. Polycystic ovary syndrome and offspring risk of congenital heart defects: a nationwide cohort study

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  3. WNT signalling in the normal human adult testis and in male germ cell neoplasms

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  4. Fetal fraction of cell-free DNA in pregnancies after fresh or frozen embryo transfer following assisted reproductive technologies

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Age-related changes in human Leydig cell status

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. WNT signalling in the normal human adult testis and in male germ cell neoplasms

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. 'Snail factors in testicular germ cell tumours and their regulation by the BMP4 signalling pathway'

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Luteinizing Hormone Receptor Is Expressed in Testicular Germ Cell Tumors: Possible Implications for Tumor Growth and Prognosis

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BACKGROUNDDDX3Y (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.METHODSDDX3Y 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.RESULTSGerm 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.CONCLUSIONSThe 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.
Original languageEnglish
JournalHuman Reproduction
Volume27
Issue number6
Pages (from-to)1547-1555
Number of pages9
ISSN0268-1161
DOIs
Publication statusPublished - 2012

ID: 34844634