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Proc Natl Acad Sci U S A. 2016 Mar 8;113(10):2666-71. doi: 10.1073/pnas.1519395113. Epub 2016 Feb 29.

Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes.

Author information

1
Center for Scientific Research, Institute of Reproductive Biomedicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China;
2
Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Jiamusi University, Jiamusi, Heilongjiang 154000, China;
3
Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.
4
Center for Scientific Research, Institute of Reproductive Biomedicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
5
Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;
6
Center for Scientific Research, Institute of Reproductive Biomedicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; hchen13@jhu.edu r_ge@yahoo.com lianqingquanmz@163.com.
7
Center for Scientific Research, Institute of Reproductive Biomedicine, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; hchen13@jhu.edu r_ge@yahoo.com lianqingquanmz@163.com.

Abstract

Testicular Leydig cells are the primary source of testosterone in males. Adult Leydig cells have been shown to arise from stem cells present in the neonatal testis. Once established, adult Leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new Leydig cells rapidly reappear. As in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new Leydig cells. As yet, the mechanisms involved in regulating the proliferation and differentiation of these stem cells remain unknown. We developed a unique in vitro system of cultured seminiferous tubules to assess the ability of factors from the seminiferous tubules to regulate the proliferation of the tubule-associated stem cells, and their subsequent entry into the Leydig cell lineage. The proliferation of the stem Leydig cells was stimulated by paracrine factors including Desert hedgehog (DHH), basic fibroblast growth factor (FGF2), platelet-derived growth factor (PDGF), and activin. Suppression of proliferation occurred with transforming growth factor β (TGF-β). The differentiation of the stem cells was regulated positively by DHH, lithium- induced signaling, and activin, and negatively by TGF-β, PDGFBB, and FGF2. DHH functioned as a commitment factor, inducing the transition of stem cells to the progenitor stage and thus into the Leydig cell lineage. Additionally, CD90 (Thy1) was found to be a unique stem cell surface marker that was used to obtain purified stem cells by flow cytometry.

KEYWORDS:

CD90; DHH; Leydig cell; stem cell; testosterone

Comment in

PMID:
26929346
PMCID:
PMC4790979
DOI:
10.1073/pnas.1519395113
[Indexed for MEDLINE]
Free PMC Article

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