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Hum Reprod. 2010 Sep;25(9):2181-7. doi: 10.1093/humrep/deq170. Epub 2010 Jul 3.

Glial cell line-derived neurotrophic factor is constitutively produced by human testicular peritubular cells and may contribute to the spermatogonial stem cell niche in man.

Author information

1
Institute for Cell Biology, Anatomy and Center for Integrated Protein Science Munich (CIPSM), Ludwig Maximilian University, Biedersteiner Strasse 29, D-80802 Munich, Germany.

Abstract

BACKGROUND:

Testicular peritubular cells form an ill-characterized cellular compartment of the human testis, which forms a border with Sertoli cells and spermatogonial stem cells (SSCs). A recently developed culture method has identified parts of the secretory repertoire of human testicular peritubular cells (HTPCs), which includes nerve growth factor. Whether peritubular cells produce glial cell line-derived neurotrophic factor (GDNF) and may thus contribute to the stem cell niche is not known.

METHODS:

We studied GDNF production in isolated peritubular cells from men with normal spermatogenesis (HTPCs) and impaired spermatogenesis and testicular fibrosis (HTPC-Fs). Human testicular biopsies and peritubular cells in culture were evaluated using immunohistochemistry, laser microdissection (LMD), RT-PCR and measurement of GDNF and cAMP by enzyme-linked immunosorbent assay. We also tested whether GDNF production is regulated by tumour necrosis factor-alpha (TNF-alpha) or tryptase, the products of mast cells or macrophages.

RESULTS:

Peritubular wall cells are in close proximity to cells expressing the GDNF family co-receptor-alpha1. GDNF mRNA was detected in LMD samples of the peritubular and tubular but not interstitial compartments. HTPCs and HTPC-Fs lack FSH- and LH-receptors but express receptors for TNF-alpha and tryptase. Importantly, peritubular cells express GDNF and constitutively released GDNF into the medium in comparably high amounts. TNF-alpha and tryptase had no effect on the secretion of GDNF by HTPCs or HTPC-Fs.

CONCLUSIONS:

Peritubular cells in testes of normal and sub-/infertile men produce GDNF and are likely constitutive contributors of the SSC niche in the human testis.

PMID:
20601681
DOI:
10.1093/humrep/deq170
[Indexed for MEDLINE]

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