International Journal of Infertility & Fetal Medicine

Register      Login

VOLUME 1 , ISSUE 1 ( September-December, 2010 ) > List of Articles

REVIEW ARTICLE

The Role of Gap Junction Proteins in Infertility

Piyush Tripathi, Manorama Tripathi

Citation Information : Tripathi P, Tripathi M. The Role of Gap Junction Proteins in Infertility. Int J Infertil Fetal Med 2010; 1 (1):11-18.

DOI: 10.5005/jp-journals-10016-1002

License: CC BY-NC 4.0

Published Online: 01-04-2013

Copyright Statement:  Copyright © 2010; The Author(s).


Abstract

Testis and ovary serve an important role of producing male and female gametes. Their normal functioning is very important for the proper formation of sperm and ovum and thus has a critical role in the successful fertility outcome. Synchronized activity of various cells in the gonads is needed to provide favorable niche for the growth and development of the germ cells. Among various ways of cellular communication, intercellular communication is mediated by gap junctions, which provides open but selective exchange of ion and molecules of restricted size between two adjoining cells. The basic unit of gap junction is connexins. Their important role has been speculated in the maintenance of homeostasis, morphogenesis, cell differentiation, and growth control in higher organisms. The expression of gap junction proteins in reproductive tissues has drawn the attention and interest of researcher to investigate their role in the reproductive outcome. The reports about the correlation of gap junction protein expression pattern in infertility patients and in animal models have suggested their implication in fertility. Some of these gap junction proteins seem to have redundant functions, whereas some could be very critical in the normal fertility and could not be dispensable for the successful outcome of the reproduction.


PDF Share
  1. Curr Pharm Des 2005;11(15):1941-58.
  2. Major involvement of connexin 43 in seminiferous epithelial junction dynamics and male fertility. Dev Biol, 2010.
  3. Gap junctions and ovarian folliculogenesis. Reproduction 2002;123(5):613-20.
  4. Proliferation of adult sertoli cells following conditional knockout of the gap junctional protein GJA1 (connexin 43) in mice. Biol Reprod 2007;76(5):804-12.
  5. A sertoli cell-specific knockout of connexin 43 prevents initiation of spermatogenesis. Am J Pathol 2007;171(1):19-31.
  6. Oogenesis defects in a mutant mouse model of oculodentodigital dysplasia. Dis Model Mech 2009;2(3-4):157-67.
  7. 5 A resolution. Nature 2009;458(7238):597-602.
  8. Emerging issues of connexin channels: Biophysics fills the gap. Q Rev Biophys 2001;34(3):325-472.
  9. Life cycle of connexins in health and disease. Biochem J, 2006;394(Pt 3):527-43.
  10. Connexins: A guide (1st ed) 2008, New York: Springer.
  11. Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development. Physiol Rev 2002;82(4):825-74.
  12. Cellular architecture of the lamina propria of human seminiferous tubules. Cell Tissue Res 1990;262(2): 253-61.
  13. Sertoli-Sertoli and Sertoli, germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocr Rev, 2004;25(5):747-806.
  14. Gap junctional communication in the male reproductive system. Biochim Biophys Acta 2005;1719(1-2):102-16.
  15. TGF beta signalling in the development of ovarian function. Cell Tissue Res 2005;322(1):107-15.
  16. Activin promotes ovarian follicle development in vitro. Endocrinology 1995;136(3): 849-56.
  17. Control of early ovarian follicular development. J Reprod Fertil Suppl 1999;54:3-16.
  18. Control of ovarian follicular development to the gonadotrophin-dependent phase: A 2006 perspective. Soc Reprod Fertil Suppl 2007;64:55-68.
  19. Generation of mouse oocytes defective in cAMP synthesis and degradation: Endogenous cyclic AMP is essential for meiotic arrest. Dev Biol, 2008;316(1):124-34.
  20. Meiotic arrest of oocytes depends on cell-to-cell communication in the ovarian follicle. Mol Cell Endocrinol 2006;252(1-2):102-06.
  21. Cloning of GJA1 (connexin43) and its expression in canine ovarian follicles throughout the estrous cycle. Gene Expr Patterns 2007;7(1-2):66-71.
  22. Connexin gene expression in seminiferous tubules of the Sprague-Dawley rat. Biol Reprod 2000;62(3):748-54.
  23. mRNA expression pattern of multiple members of connexin gene family in normal and abnormal fetal gonads in mouse. Indian J Physiol Pharmacol 2003;47(2):147-56.
  24. Expression and localization of gap junctional connexins 26 and 43 in bovine periovulatory follicles and in corpus luteum during different functional stages of oestrous cycle and pregnancy. Reprod Domest Anim 2009;44(2):295-302.
  25. Identification and expression analysis of CX45 and CX60 as major connexins in porcine oocytes. J Anim Sci 2010.
  26. Differential expression of gapjunction gene connexin 31 in seminiferous epithelium of rat testes. FEBS Lett 1999;453(3):243-48.
  27. Connexin 43 a potential regulator of cell proliferation and apoptosis within the seminiferous epithelium. Int J Biochem Cell Biol 2009;41(6):1381-90.
  28. Connexin 33: A rodent-specific member of the gap junction protein family? J Androl 2005;26(1):75-84.
  29. Connexin 33 impairs gap junction functionality by accelerating connexin 43 gap junction plaque endocytosis. Traffic 2009;10(9):1272-85.
  30. A role for an inhibitory connexin in testis? Dev Biol 1996;175(1):50-56.
  31. Heteromeric connexin 43/connexin 33 complex endocytosis: A connexin phosphorylation independent mechanism. Biochimie 2010;92(5):555-59.
  32. Connexin43 gene expression and regulation in the rodent seminiferous epithelium. J Histochem Cytochem 2000;48(6):793-805.
  33. Functional characterization of Cx43 based gap junctions during spermatogenesis. J Cell Physiol 2004;200(1):146-54.
  34. Cortactin/tyrosinephosphorylated cortactin interaction with connexin 43 in mouse seminiferous tubules. Microsc Res Tech 2009;72(11):856-67.
  35. Connexin43 in rat oocytes: Developmental modulation of its phosphorylation. Biol Reprod 2002;66(3):568-73.
  36. Dynamic changes of gap junctions and cytoskeleton during in vitro culture of cattle oocyte cumulus complexes. Biol Reprod 1993;49(6):1277-87.
  37. Cell Commun Adhes 2006;13(1-2):61-77.
  38. Selective assembly of connexin 37 into heterocellular gap junctions at the oocyte/granulosa cell interface. J Cell Sci 2004;117(Pt 13):2699-707.
  39. Differential expression and localization of connexin-37 and connexin-43 in follicles of different stages in the 4-week-old mouse ovary. Mol Cell Endocrinol 2005;234 (1-2):27-35.
  40. Expression of gap junctional proteins connexin 43, 32 and 26 throughout follicular development and atresia in cows. Endocrine 1999;10(1):43-51.
  41. Expression of gap junctional connexins 26, 32 and 43 mRNA in ovarian preovulatory follicles and corpora lutea in sheep. Can J Physiol Pharmacol 2006;84(10):1011-20.
  42. Molecular cloning and functional expression of the mouse gap junction gene connexin-57 in human HeLa cells. J Biol Chem 1999;274(21):14716-23.
  43. Isolation and characterization of a novel connexin gene, Cx-60, in porcine ovarian follicles. Endocrinology 1998;139(1):320-29.
  44. Modified expression of testicular gap-junction connexin 43 during normal spermatogenic cycle and in altered spermatogenesis. Cell Tissue Res 1999;298(1):113-21.
  45. Contraceptive steroids from pharmaceutical waste perturbate junctional communication in Sertoli cells. Biochimie 2009;91(11-12):1366-75.
  46. Follicle-stimulating hormone increases gap junction communication in Sertoli cells from immature rat testis in primary culture. J Membr Biol 1994;139(2):81-96.
  47. Putative second messengers affect cell coupling in the seminiferous tubules. Cell Biol Int Rep 1986;10(8):631-39.
  48. Ultrastructural and biochemical evidence for gap junction and connexin 43 expression in a clonal Sertoli cell line: A potential model in the study of junctional complex formation. Cell Tissue Res 1998;294(2):279-87.
  49. Three-dimensional analysis of connexin 43 gap junction in the ex vivo rat seminiferous tubules: Short-term effects of hormonal effectors. Microsc Res Tech 2009;72(11): 845-55.
  50. Myometrial transcriptional regulation of the gap junction gene, connexin-43. Reprod Fertil Dev 1995;7(3):603-11.
  51. 17beta-estradiol induces the translocation of the estrogen receptors ESR1 and ESR2 to the cell membrane, MAPK3/1 phosphorylation and proliferation of cultured immature rat Sertoli cells. Biol Reprod 2008;78(1):101-14.
  52. Adult testicular enlargement induced by neonatal hypothyroidism is accompanied by increased Sertoli and germ cell numbers. Endocrinology 1993;132(6):2607-13.
  53. Neonatal hypothyroidism alters the localization of gap junctional protein connexin 43 in the testis and messenger RNA levels in the epididymis of the rat. Biol Reprod 2003;68(4):1232-40.
  54. Identification of novel genes expressed during spermatogenesis in stage-synchronized rat testes by differential display. Biochem Biophys Res Commun 2003; 307(4):782-90.
  55. Developmental expression and regulation of the gap junction protein and transcript in rat ovaries. Mol Reprod Dev 1997;47(3):231-39.
  56. Phosphorylation and expression of connexin- 43 ovarian gap junction protein are regulated by luteinizing hormone. J Biol Chem, 1994;269(48):30502-09.
  57. Luteinizing hormone-induced connexin 43 downregulation: Inhibition of translation. Endocrinology 2004;145(4):1617-24.
  58. Coexpression of gap junction proteins in the cumulus-oocyte complex. Mol Reprod Dev 1993;36(1):7-15.
  59. Defects in the germ line and gonads of mice lacking connexin43. Biol Reprod 1999;60(5):1263-70.
  60. Primordial germ cell deficiency in the connexin 43 knockout mouse arises from apoptosis associated with abnormal p53 activation. Development 2006;133(17):3451-60.
  61. A potential novel mechanism involving connexin 43 gap junction for control of sertoli cell proliferation by thyroid hormones. J Cell Physiol 2006;209(1):153-61.
  62. Connexin31-deficiency in mice causes transient placental dysmorphogenesis but does not impair hearing and skin differentiation. Dev Biol 2001;231(2):334-47.
  63. Biological functions of connexin genes revealed by human genetic defects, dominant negative approaches and targeted deletions in the mouse. Novartis Found Symp 199921976-88. discussion 88-96.
  64. Connexin 43 expression in the testis of the frog Rana esculenta. Zygote 2006;14(4):349-57.
  65. Connexin 43 expression in human and mouse testes with impaired spermatogenesis. Eur J Histochem 2007;51(4):261-68.
  66. Female infertility in mice lacking connexin 37. Nature 1997;385(6616):525-59.
  67. Differential contributions of connexin37 and connexin43 to oogenesis revealed in chimeric reaggregated mouse ovaries. J Cell Sci 2005;118(Pt 21):5071-78.
  68. Oocyte-directed depletion of connexin 43 using the Cre-LoxP system leads to subfertility in female mice. Dev Biol 2008;313(1):1-12.
  69. Freeze-fracture observations on the intercellular junctions of Sertoli cells and of Leydig cells in the human testis. Cell Tissue Res 1976;166(1):37-48.
  70. Gap junctions between Sertoli cells in the infertile human testis. Fertil Steril 1977;28(7):755-58.
  71. Expression of connexin 43 in human testis. Histochem Cell Biol 1999;112(3):215-20.
  72. Impaired gap junction connexin 43 in Sertoli cells of patients with secretory azoospermia: A marker of undifferentiated Sertoli cells. Lab Invest 2003;83(3):449-56.
  73. Replacement of connexin 43 by connexin 26 in transgenic mice leads to dysfunctional reproductive organs and slowed ventricular conduction in the heart. BMC Dev Biol 2007;7:26.
  74. Mutations in GJA1 (connexin 43) are associated with non-syndromic autosomal recessive deafness. Hum Mol Genet 2001;10(25):2945-51.
  75. Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am J Hum Genet 2003;72(2):408-18.
  76. GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype. Hum Mutat 2009;30(5):724-33.
  77. A dominant loss-of-function GJA1 (Cx43) mutant impairs parturition in the mouse. Biol Reprod 2009;80(6):1099-106.
  78. Cell, age and stage-dependent distribution of connexin 43 gap junctions in testes. J Cell Sci 1992;103(Pt 1):81-96.
  79. Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin 32-deficient mice. Proc Natl Acad Sci. USA 1996;93(18):9565-70.
  80. Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin 40-deficient mice. Curr Biol 1998;8(5):299-302.
  81. Impaired conduction in the bundle branches of mouse hearts lacking the gap junction protein connexin40. Circulation 2001;103(11):1591-98.
  82. et al. Cardiac malformation in neonatal mice lacking connexin 43. Science 1995;267(5205):1831-34.
  83. Unique and shared functions of different connexins in mice. Curr Biol 2000;10(18):1083-91.
  84. Targeted ablation of connexin 50 in mice results in microphthalmia and zonular pulverulent cataracts. J Cell Biol 1998;143(3):815-25.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.