Gene expression profiling of puberty-associated genes reveals abundant tissue and sex-specific changes across postnatal development

Abstract

The timing of human puberty is highly variable, sexually dimorphic, and associated with adverse health outcomes. Over 20 genes carrying rare mutations have been identified in known pubertal disorders, many of which encode critical components of the hypothalamic-pituitary-gonadal (HPG) axis. Recent genome-wide association studies (GWAS) have identified more than 100 candidate genes at loci associated with age at menarche or voice breaking in males. We know little about the spatial, temporal or postnatal expression patterns of the majority of these puberty-associated genes. Using a high-throughput and sensitive microfluidic quantitative PCR strategy, we profiled the gene expression patterns of the mouse orthologs of 178 puberty-associated genes in male and female mouse HPG axis tissues, the pineal gland, and the liver at five postnatal ages spanning the pubertal transition. The most dynamic gene expression changes were observed prior to puberty in all tissues. We detected known and novel tissue-enhanced gene expression patterns, with the hypothalamus expressing the largest number of the puberty-associated genes. Notably, over 40 puberty-associated genes in the pituitary gland showed sex-biased gene expression, most of which occurred peri-puberty. These sex-biased genes included the orthologs of candidate genes at GWAS loci that show sex-discordant effects on pubertal timing. Our findings provide new insight into the expression of puberty-associated genes and support the possibility that the pituitary plays a role in determining sex differences in the timing of puberty.

Genomic signatures of fine‐scale local selection in Atlantic salmon suggest involvement of sexual maturation, energy homeostasis and immune defence‐related genes

“…Six6 is also an important regulator of fertility in mammals of both sexes, via its effect on gonadotropin-releasing hormone production by the hypothalamus (Larder, Clark, Miller, & Mellon, 2011). Correspondingly, like vgll3, it is implicated in human pubertal timing (Hou et al, 2017). Barson et al (2015) did not find any nonsynonymous mutations in the six6 coding region, and results indicate that the selective target could be a regulatory element for this gene.…”

“…Six6 is also an important regulator of fertility in mammals of both sexes, via its effect on gonadotropin‐releasing hormone production by the hypothalamus (Larder, Clark, Miller, & Mellon, ). Correspondingly, like vgll3 , it is implicated in human pubertal timing (Hou et al., ). Barson et al.…”

Genomic Signatures of Fine-Scale Local Adaptation in Atlantic Salmon Suggest Involvement of Sexual Maturation, Energy Homeostasis, Behaviour, and Immune Defence-Related Genes

“…In addition to vgll3 and six6 , several other genes implicated in human pubertal timing (Hou et al, 2017) are associated with PC2 SNPs. These include neuronal growth regulator 1 ( negr1 , Ssa10), linked to both obesity and sexual maturation in several taxa (Lee et al, 2012); trmt11 (Ssa05); ptprf (Ssa10); ntrk2 (Ssa10); lgr4 (Ssa11); ptprd (Ssa18); kcnk9 (Ssa27); and h6st1 (Ssa29) (Table S4).…”

Gene expression changes associated with trajectories of psychopathology in a longitudinal cohort of children and adolescents

“…We consider that differentially regulated genes in the H-H or L-L groups are probably related to normal trajectory of development, puberty, though some previous studies did not associate these genes with it 26,27 , or to the maintenance of the symptoms of chronic mental disorders or at least not related to a change of status concerning mental disorders. Thus, we focused on genes that were exclusively differentially expressed in the L-H and H-L groups.…”