Failure of Spermatogenesis in Mice Lacking Connexin431

Abstract

Connexin43 (Cx43), a gap junction protein encoded by the Gja1 gene, is expressed in several cell types of the testis. Cx43 gap junctions couple Sertoli cells with each other, Leydig cells with each other, and spermatogonia/spermatocytes with Sertoli cells. To investigate the role of this communication pathway in spermatogenesis, we studied postnatal testis development in mice lacking Cx43. Because such mice die shortly after birth, it was necessary to graft testes from null mutant fetuses under the kidney capsules of adult males for up to 3 wk. Grafted wild-type testes were used as controls. In our initial experiments with wild-type testes, histological examination indicated that the development of grafted testes kept pace with that of nongrafted testes in terms of the onset of meiosis, but this development required the presence of the host gonads. When excised grafts were stimulated in vitro with cAMP or LH, there was no significant difference in androgen production between null mutant and wild-type testes, indicating that the absence of Cx43 had not compromised steroidogenesis. Previous research has shown that Cx43 null mutant neonates have a germ cell deficiency that arises during fetal life, and our analysis of grafted testes demonstrated that this deficiency persists postnatally, giving rise to a "Sertoli cell only" phenotype. These results indicate that intercellular communication via Cx43 channels is required for postnatal expansion of the male germ line.

Functional analysis of gap junctions in ovarian granulosa cells: distinct role for connexin43 in early stages of folliculogenesis

“…In addition to dysmorphogenesis of the heart leading to early neonatal death (31,38), offspring lacking Cx43 exhibit pathophysiological features in a variety of organs. These include slowed cardiac conduction and increased susceptibility to arrhythmias (8,14,22), precataractogenic lesions in the lenses (12), delayed ossification and osteoblast dysfunction (21), impaired hematopoiesis (27), reduced germ cell numbers in the fetal gonads (17), and disrupted gametogenesis in both sexes (1,32). It is the latter consequence of the loss of Cx43 that is the focus of the present report.…”

Biological effects of FoxJ2 over-expression

“…The knockout Cx-43 has been reported to produce cardiac malformations (Ya et al 1998;Reaume et al 1995). Defects in the germ line and gonads (Juneja et al 1999) and failure of spermatogenesis (Roscoe et al 2001) were also observed in mice lacking Cx-43. However, overexpression of Cx-43 also produces similar heart defects (Ewart et al 1997).…”

Fertility and spermatogenesis are altered in α1b-adrenergic receptor knockout male mice

“…Similar morphological alterations of Sertoli cells were described in other germ cell-depleted situations as in jsd/jsd mice (Tohda et al 2001), ERKO male mice (Eddy et al 1996), or in rats treated with Sertoli cell toxicants (Hild et al 2001). The early arrest in spermatogenesis, as a consequence of the formation of the vacuolated structures in the Sertoli cells, was also emphasized in mice deficient in inositol polyphosphate 5-phosphatase (Hellsten et al 2002), or in mice lacking connexin 43 (Roscoe et al 2001). In these models, it was suggested that massive vacuolization of Sertoli cells impairs the functional interactions between maturing germ cells and Sertoli cells, thus causing the germ cell apoptosis.…”