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Connexin 43 a check-point component of cell proliferation implicated in a wide range of human testis diseases

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Abstract

Gap junction channels link cytoplasms of adjacent cells. Connexins, their constitutive proteins, are essential in cell homeostasis and are implicated in numerous physiological processes. Spermatogenesis is a sophisticated model of germ cell proliferation, differentiation, survival, and apoptosis, in which a connexin isotype, connexin 43, plays a crucial role as evidenced by genomic approaches based on gene deletion. The balance between cell proliferation/differentiation/apoptosis is a prerequisite for maintaining levels of spermatozoa essential for fertility and for limiting anarchic cell proliferation, a major risk of testis tumor. The present review highlights the emerging role of connexins in testis pathogenesis, focusing specifically on two intimately interconnected human testicular diseases (azoospermia with impaired spermatogenesis and testicular germ cell tumors), whose incidence increased during the last decades. This work proposes connexin 43 as a potential cancer diagnostic and prognostic marker, as well as a promising therapeutic target for testicular diseases.

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Abbreviations

AFP:

Alpha-fetoprotein

AMH:

Anti-Müllerian hormone

BTB:

Blood–testis barrier

cAMP:

Cyclic adenosine monophosphate

cGMP:

Cyclic guanosine monophosphate

CIS:

Carcinoma in situ

Cx:

Connexin

G-CSF:

Granulocyte colony-stimulating factor

GJA1:

Gap junction protein alpha 1

GJIC:

Gap junction intercellular communication

hCG:

Human chorionic gonadotropin

KO:

Knock-out

LDH:

Lactate dehydrogenase

miRNA:

MicroRNA

ODDD:

Oculodentodigital

PGC:

Primordial germ cell

PLAP:

Placental alkaline phosphatase

SCO:

Sertoli-cell-only

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Acknowledgments

The preparation of this review was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM). The authors would like to thank Laure Gilleron for critically reading the manuscript and Jeannine Colombani for secretarial assistance. JG is a doctoral and postdoctoral research fellow of the French Ministry of Research and Technology and of EMBO.

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Authors and Affiliations

  1. Department of Urology, Pasteur Hospital, Nice, France

    Daniel Chevallier

  2. INSERM U 1065, Team 5 “Physiopathologic Control of Germ Cell Proliferation: Genomic and Non Genomic Mechanisms”, University Nice Sophia-Antipolis, C3M, 151 route Saint-Antoine de Ginestière BP 2 3194, Nice Cedex 3, 06204, France

    Daniel Chevallier, Jérome Gilleron & Georges Pointis

  3. UMR S775, University Paris Descartes, 45 rue des Saints Pères, Paris, 75006, France

    Diane Carette & Dominique Segretain

  4. University of Versailles, Saint Quentin, 78035, France

    Diane Carette & Dominique Segretain

  5. Max Planck Institute of Molecular Cell Biology and Genetics, 01307, Dresden, Germany

    Jérome Gilleron

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  1. Daniel Chevallier
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  2. Diane Carette
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  3. Dominique Segretain
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  4. Jérome Gilleron
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  5. Georges Pointis
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Correspondence to Georges Pointis.

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Chevallier, D., Carette, D., Segretain, D. et al. Connexin 43 a check-point component of cell proliferation implicated in a wide range of human testis diseases. Cell. Mol. Life Sci. 70, 1207–1220 (2013). https://doi.org/10.1007/s00018-012-1121-3

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  • DOI: https://doi.org/10.1007/s00018-012-1121-3

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