Role of connexin-based gap junction channels in testis

doi:10.1016/j.tem.2005.07.001

Trends in Endocrinology & Metabolism

Volume 16, Issue 7, September 2005, Pages 300-306

https://doi.org/10.1016/j.tem.2005.07.001 Get rights and content

Spermatogenesis is a highly controlled process that allows proliferation and differentiation of male germ cells. This is under classical endocrine and paracrine controls. There is also evidence that gap junctions between Leydig cells, between Sertoli cells and between Sertoli and germ cells participate in the local regulation of spermatogenesis. Recent studies reveal that connexin 43 (Cx43), the predominant gap junction protein in the testis, is essential for the initiation and maintenance of spermatogenesis. In this review, we focus on the identification, distribution and control of connexins in the mammalian testis. The implication of connexin-based gap junctions in testicular physiology and in pathological disorders of spermatogenesis (spermatogenic arrest and testis cancer) is also discussed.

Section snippets

Gap junction channels and their constitutive proteins: connexins

Gap junctions are intercellular, plasma-membrane channels that link the cytoplasm of neighboring cells in numerous tissues except erythrocytes, platelets, fully differentiated skeletal muscle cells and sperm. They allow the direct exchange of molecules with a relative molecular mass up to 1 kDa, such as metabolic precursors, nutrients and second messengers including inositol (1,4,5)-triphosphate [Ins(1,4,5)P₃], cAMP and ions [3]. This process of exchange of molecular signals, also termed

Gap junctions and Cxs in the testis

Gap junctions were identified first by electron microscopy in the testis of rodents before and during the initiation of spermatogenesis [10]. In the mature rat testis, transcripts for 11 Cxs have been identified (Cx26, Cx30.2, Cx31, Cx31.1, Cx32, Cx33, Cx37, Cx40, Cx43, Cx46 and Cx50), 10 of these are present in polysomes and are, presumably, translated [11].

GJIC occurs between Leydig cells, which express only Cx43 12, 13, 14. In seminiferous tubules, gap junctions are located between Sertoli

Physiological relevance of gap junctions and Cxs in the testis

The possibility that Cx43 plays a primordial role in gonadal development and the control of spermatogenesis results from observations in both fertile and mutant, sterile animals, and in mice in which the genes encoding Cxs are deleted. Cx43 forms intercellular contacts between Sertoli cells and germ cells in proliferation [20] and Cx43-based gap junctions appear to be controlled in a stage-dependent manner, which indicates a close relationship between the association of specific germ cells and

Control of Cx expression in the testis

Despite the well-documented presence and indispensability of Cx43, there is limited information regarding how GJIC and Cxs are regulated in the testis. A schematic illustration of Cx gap junction control in the testis is presented in Figure 2. There is evidence that the expression of Cx43 depends on the stage of the spermatogenic cycle in rat 15, 16, 19, 25, 47, 48 and human testes 17, 18. In mutant mice with impaired spermatogenesis, a close relationship between the presence of specific germ

Gap junctions and Cx43 expression in testicular diseases

Mutations in genes that encode Cxs result in human genetic disorders [7], and impaired GJIC and a lack of transcription of Cx genes correlate with neoplastic transformation in several human tissues 63, 64. To date, there is limited information on gap junctions in pathological testes. Freeze-fracture studies show no variation in the number of gap-junctional particles in the seminiferous tubules of azoospermic and oligospermic patients [65]. However, there is no information on the origin and

Concluding remarks and future perspectives

In addition to the classical functions of Sertoli cells, the data presented in this review highlight a new type of Sertoli–germ cell communication that appears to be essential for spermatogenesis. If the involvement of Sertoli–germ cell communication is associated mainly with the presence of Cx43, the function of native Cx33, which exhibits a dominant-negative effect on GJIC, remains to be defined. The lack of Cx33 ortholog in the human genome [7] does not, however, mean that another member of

Acknowledgements

This work was supported, in part, by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM) and by Pfizer. The authors thank A. Malassine and J-M. Gasc for critically reading the manuscript.

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Trends in Endocrinology & Metabolism

Role of connexin-based gap junction channels in testis

Section snippets

Gap junction channels and their constitutive proteins: connexins

Gap junctions and Cxs in the testis

Physiological relevance of gap junctions and Cxs in the testis

Control of Cx expression in the testis

Gap junctions and Cx43 expression in testicular diseases

Concluding remarks and future perspectives

Acknowledgements

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Curr. Biol.

Dev. Biol.

Curr. Opin. Cell Biol.

Cell Biol. Int. Rep.

Biochem. Biophys. Res. Commun.

Reprod. Toxicol.

Biol. Cell.

Fertil. Steril.

Biochim. Biophys. Acta

Germ cell-somatic cell interactions during spermatogenesis

Reprod. Suppl.

Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis

Endocr. Rev.

The cellular Internet: on-line with connexins

Bioessays

Innexins get into the gap

Bioessays

An update on connexin genes and their nomenclature in mouse and man

Cell Commun. Adhes.

Functional analysis of selective interactions among rodent connexins

Mol. Biol. Cell

Plasma membrane channels formed by connexins: their regulation and functions

Physiol. Rev.

Morphological and functional evidence for Sertoli-germ cell relationships

Connexin gene expression in seminiferous tubules of the Sprague-Dawley rat

Biol. Reprod.

Intercellular communication between mouse Leydig cells

Am. J. Physiol.

Characterization of gap junctions between pairs of Leydig cells from mouse testis

Am. J. Physiol.

Cell-, age- and stage-dependent distribution of connexin43 gap junctions in testes

J. Cell Sci.

Modified expression of testicular gap-junction connexin 43 during normal spermatogenic cycle and in altered spermatogenesis

Cell Tissue Res.

Expression of connexin 43 in human testis

Histochem. Cell Biol.

Connexin43 gene expression and regulation in the rodent seminiferous epithelium

J. Histochem. Cytochem.

Functional characterization of Cx43 based gap junctions during spermatogenesis

J. Cell. Physiol.