Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex-biased gene expression of amygdala in sheep

ABSTRACT: Background: The exact nature of the interrelationship between pubertal brain development and hormones involvement has always attracted wide interest. Brain structural changes that occur during the pubertal developmental process mainly appear in the regions most closely linked with emotion, motivation and cognitive functions. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin-releasing hormone (GnRH) receptors results in increased sex-differences in cognitive executive function and emotional control, as well as in a sex- and side-specific gene expression pattern of hippocampal genes associated with synaptic plasticity and endocrine signaling. In this study, we explore the effects of this treatment regime on the amygdalar gene expression profile. Methods: The study was conducted with 30 same-sex twin lambs (14 female and 16 male), half of which were treated with the GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty, until 50 weeks of age. The gene expression profiles of left and right amygdala samples from all 30 animals were measured by using ovine 8 X 15 K Agilent microarrays. Furthermore, differential expression of a selected number of genes was confirmed by qRT-PCR (Quantitative real time PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed with the Ingenuity Pathway Analysis (IPA), version 7.5 DAVID (Database for Annotation, Visualization and integrated Discovery) software packages respectively. Results: GnRHa treatment was associated with significant sex- and hemisphere-specific differential expression of genes. Interestingly, genome-wide transcription showed a set of 438 (p value <0.05) genes in female treated left and 46 (p value <0.0.5) genes in females treated right amygdala were differentially expressed but not in any treatment group of male animals. Conclusion: Our results indicate that GnRH directly and/or indirectly is involved in the regulation of sex- and side-specific differential expression of genes in amygdala. Hence, this finding should be considered when long-term peri-pubertal GnRHa treatment is used in children.

ORGANISM(S): Ovis aries

PROVIDER: GSE44202 | GEO | 2013/05/31

SECONDARY ACCESSION(S): PRJNA195546

REPOSITORIES: GEO