Abstract
The Lin28/let-7 system, which includes the RNA-binding proteins, Lin28a/Lin28b, and let-7 miRNAs, has emerged as putative regulator of puberty and male gametogenesis; yet, its expression pattern and regulation in postnatal testis remain ill defined. We report herein expression profiles of Lin28 and let-7 members, and related mir-145 and mir-132, in rat testis during postnatal maturation and in models of altered puberty and hormonal deregulation. Neonatal expression of Lin28a and Lin28b was low and rose markedly during the infantile period; yet, expression patterns diverged thereafter, with persistently elevated levels only for Lin28b, which peaked at puberty. Let-7a, let-7b, mir-132 and mir-145 showed profiles opposite to Lin28b. In fact, let-7b and mir-145 were abundant in pachytene spermatocytes, but absent in elongating spermatids, where high expression of Lin28b was previously reported. Perturbation of puberty by neonatal estrogenization reverted the Lin28/let-7 expression ratio; expression changes were also detected in other models of delayed puberty, due to early photoperiod or nutritional manipulations. In addition, hypophysectomy or growth hormone (GH) deficiency revealed regulation of this system by gonadotropins and GH. Our data document the expression profiles of the Lin28/let-7 system in rat testis along postnatal/pubertal maturation, and their perturbation in models of pubertal and hormonal manipulation.
Highlights
The heterochronic gene, Lin[28], was first identified in the nematode, Caenorhabditis elegans, where it displays tissue- and stage-specific patterns of expression[1]
The complexity of this regulatory system is illustrated by the fact that Lin28a/Lin28b redundantly represses the synthesis of mature let-7 miRNAs, which in turn are able to suppress Lin[28] levels, creating a double-negative feedback loop
Previous literature and bioinformatic analyses of our group had documented the putative regulatory role in this hub of mir-145 and mir-132, which is highly conserved across most vertebrates
Summary
The heterochronic gene, Lin[28], was first identified in the nematode, Caenorhabditis elegans, where it displays tissue- and stage-specific patterns of expression[1]. Recent evidence has unveiled the central position of Lin28a/Lin28b within a key regulatory network involving c-Myc and let-79–12; let-7 miRNAs being highly conserved across phyla, and widely and abundantly expressed in numerous species[13]. Shinoda et al demonstrated that conditional Lin28a or Lin28b deletion during fetal period, but not during the neonatal period or adulthood, resulted in growth defects and aberrations in glucose metabolism They observed that Lin28b regulates growth in mice in a gender-specific manner, since Lin28b KO males, but not females, showed post-natal dwarfism[26]. We characterize changes in the expression patterns of these elements in various models of altered puberty and study the role of different hormonal axes, including the gonadotropic system, in the regulation of their testicular expression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
