Abstract
BackgroundOnset of spermatogenesis at puberty is critically dependent on the activity of hypothalamic-pituitary-gonadal axis and testosterone production by Leydig cells. The aim of this study was to examine whether activation of Notch receptors and expression of Notch ligands and effector genes in rat seminiferous epithelium are controlled by androgen signaling during puberty.MethodsPeripubertal (5-week-old) Wistar rats received injections of flutamide (50 mg/kg bw) daily for 7 days to reduce androgen receptor (AR) signaling or a single injection of ethanedimethane sulphonate (EDS; 75 mg/kg bw) to reduce testosterone production. Gene and protein expressions were analyzed by real-time RT-PCR and western blotting, respectively, protein distribution by immunohistochemistry, and steroid hormone concentrations by enzyme-linked immunosorbent assay. Statistical analyses were performed using one-way ANOVA followed by Tukey’s post hoc test or by Kruskal-Wallis test, followed by Dunn’s test.ResultsIn both experimental models changes of a similar nature in the expression of Notch pathway components were found. Androgen deprivation caused the reduction of mRNA and protein expression of DLL4 ligand, activated forms of Notch1 and Notch2 receptors and HES1 and HEY1 effector genes (p < 0.05, p < 0.01, p < 0.001). In contrast, DLL1, JAG1 and HES5 expressions increased in seminiferous epithelium of both flutamide and EDS-treated rats (p < 0.05, p < 0.01, p < 0.001).ConclusionsAndrogens and androgen receptor signaling may be considered as factors regulating Notch pathway activity and the expression of Hes and Hey genes in rat seminiferous epithelium during pubertal development. Further studies should focus on functional significance of androgen-Notch signaling cross-talk in the initiation and maintenance of spermatogenesis.
Highlights
Onset of spermatogenesis at puberty is critically dependent on the activity of hypothalamic-pituitarygonadal axis and testosterone production by Leydig cells
Efficacy of androgen deprivation by flutamide or ethanedimethane sulphonate (EDS) was examined through analysis of luteinizing hormone receptor (LHR; marker of Leydig cells), plasma testosterone concentrations, and the expression of three genes regulated by androgens in Sertoli cells, Rhox5, PCI and Cldn11 [33]
Short-term androgen signaling disruption models used allowed for efficient androgen signaling reduction without producing profound alterations in germ cell composition in seminiferous epithelium of peripubertal males
Summary
Onset of spermatogenesis at puberty is critically dependent on the activity of hypothalamic-pituitarygonadal axis and testosterone production by Leydig cells. Onset of spermatozoa production at puberty is critically dependent on the activity of hypothalamic-pituitarygonadal axis and testosterone production by Leydig cells [1]. The majority of evidence indicates that differentiating germ cells do not express the AR and Sertoli cells are considered as major mediators of androgen action in the control of spermatogenesis [2]. At puberty onset androgens drive Sertoli cell maturation, repressing antyműllerian hormone (AMH) expression and controlling the formation of blood-testis barrier. Maintenance and dynamics of the blood-testis barrier, as well as Sertoli cell–spermatid adhesion and sperm release from seminiferous epithelium (spermiation) are dependent on androgen action in Sertoli cells [1]
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