Hypothalamus transcriptome during the early rise in LH secretion related to puberty age in bull calves

Abstract

In prepubertal bull calves there is an early transient rise in gonadotropin secretion between 10 and 20 weeks of age. The early elevation in mean circulating concentrations of LH and FSH most likely causes the proliferation of Sertoli and Leydig cells, respectively. This postnatal gonadotropin rise it is considered one of the main factors in determining the age at which bulls reach puberty (Brito et al., 2007). In order to contribute our understanding of the genes and regulatory pathways involved in this phenomenon, we characterized the hypothalamus transcriptome from six Angus calves along this early expression pattern of LH (4, 6 and 14 wk of age). Of 37 million RNA-Seq reads per sample generated using the Illumina HiSeq 2000 sequencer, at least 95% were mapped to the customized reference genome BosTau6. The Gene annotation revealed that 13976 genes were expressed in the hypothalamus libraries. Tophat2, EdgeR, DESeq2, Bioconductor and R packages were utilized to performed differential expression analysis between groups. We detected 915 differentially expressed genes (P adjusted < 0.05). The top gene ontology term enrichment of the highest expressed genes in the hypothalamus included cellular synapse, ion chanel complex, neuron projection and plasma membrane part (Cellular component category); cell-cell signaling, transmembrane transport, behavior and organism process (Biological process); metal ion transmembrane transporter activity and neuropeptide hormone activity (Molecular function). Enrichment analysis identified 40 KEGG significantly enriched pathways. Based on the observation of the lowest P-value, calcium, oxytocin, circadian entrainment, cholinergic glutamatergic, dopaminergic, serotonergic and GABAergic synapse, GnRH, Estrogen, Rap1, MAPK, ErbB, Ras and cancer signaling and several drugs addiction were among the most important enriched pathways. At the top list the DGs we found a group of genes including the homeodomain transcription factor Orthopedia OTP and the coregulated genes AVP, OXT, CRH and TH known for their physiological roles associated with lactation and mammalian social behaviors.