A deficiency of lunatic fringe is associated with cystic dilation of the rete testis

Abstract

Lunatic fringe belongs to a family of β1–3 N-acetyltransferases that modulate the affinity of the Notch receptors for their ligands through the elongation of O-fucose moieties on their extracellular domain. A role for Notch signaling in vertebrate fertility has been predicted by the intricate expression of the Notch receptors and their ligands in the oocyte and granulosa cells of the ovary and the spermatozoa and Sertoli cells of the testis. It has been demonstrated that disruption of Notch signaling by inactivation of lunatic fringe led to infertility associated with pleiotropic defects in follicle development and meiotic maturation of oocytes. Lunatic fringe null males were found to be subfertile. Here, we report that gene expression data demonstrate that fringe and Notch signaling genes are expressed in the developing testis and the intratesticular ductal tract, predicting roles for this pathway during embryonic gonadogenesis and spermatogenesis. Spermatogenesis was not impaired in the majority of the lunatic fringe null males; however, spermatozoa were unilaterally absent in the epididymis of many mice. Histological and immunohistochemical analysis of these testes revealed the development of unilateral cystic dilation of the rete testis. Tracer dye experiments confirm a block in the connection between the rete testis and the efferent ducts. Further, the dye studies demonstrated that many lunatic fringe mutant males had partial blocks of the connection between the rete testis and the efferent ducts bilaterally.

Notch signaling represses GATA4-induced expression of genes involved in steroid biosynthesis

“…Notch signaling is important for the development of the male reproductive tract, and Leydig cells particularly (Dirami et al , 2001; Tang et al , 2008; Hahn et al , 2009; Defalco et al , 2013). Perturbation of Notch signaling in granulosa cells results in MOFs, defective meiotic maturation and loss of oocytes (Hahn et al , 2005; Trombly et al , 2008; Manosalva et al , 2013; Xu and Gridley, 2013; Vanorny et al , 2014).…”

Dynamics of Notch Pathway Expression during Mouse Testis Post-Natal Development and along the Spermatogenic Cycle

“…In rodents and humans, aberrant Notch activity was associated with male infertility [17], [19], [21], [22], [24], [25]. However, other studies [23], [26] reported that most of Notch pathway components are not transcribed in the mouse testis and that Notch blockage in germ and Sertoli cells had no effect on spermatogenesis.…”

Lunatic, Manic, and Radical Fringe Each Promote T and B Cell Development

“…While loss of Lfng may cause perinatal lethality, Lfng null homozygotes in a FVB/C57BL/6 mixed genetic background live for several months, although they are small, lack a tail, and are infertile (20–22). Deletion of Mfng or Rfng separately or together has no obvious effects on development or fertility (20, 23, 24).…”