Connexin 43 a check-point component of cell proliferation implicated in a wide range of human testis diseases
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Cellular and Molecular Life Sciences
REVIEW
Connexin 43 a check-point component of cell proliferation implicated in a wide range of human testis diseases Daniel Chevallier • Diane Carette • Dominique Segretain Je´rome Gilleron • Georges Pointis
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Received: 25 June 2012 / Revised: 6 August 2012 / Accepted: 7 August 2012 Ó Springer Basel AG 2012
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
D. Chevallier Department of Urology, Pasteur Hospital, Nice, France D. Chevallier J. Gilleron G. Pointis (&) 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 Ginestie`re BP 2 3194, Nice Cedex 3 06204, France e-mail: [email protected] D. Carette D. Segretain UMR S775, University Paris Descartes, 45 rue des Saints Pe`res, Paris 75006, France D. Carette D. Segretain University of Versailles, Saint Quentin 78035, France J. Gilleron Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
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. Keywords Azoospermia Connexin 43 Gap junction Pathogenesis Testicular germ cell tumors Abbreviations AFP Alpha-fetoprotein AMH Anti-Mu¨llerian 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
Introduction Disruption of testis development and of spermatogenesis, consequently to neonatal exposure to endocrine disrupters, is now widely recognized [1]. Identification of the mechanisms that drive these features is important because fetal
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exposure is held responsible for the increasing incidence of male infertility and
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