Litter size is an important indicator to measure the reproductive performance of goats, which is affected by the reproductive function of animals. The hypothalamus, as the regulatory center of the endocrine system, plays an important role in the reproduction of female animals. Here, we performed high-throughput RNA sequencing using hypothalamic tissue from high-fecundity and low-fecundity Leizhou goats to explore critical functional genes associated with litter size. Differentially expressed mRNA, lncRNA, and circRNAs were screened using DESeq and were enriched, and then analyzed by Gene Ontology and Kyoto Encyclopedia of Gene and Genome. Results showed that some of these differentially expressed mRNAs could be enriched in reproductive processes, jak-STAT, prolactin signaling pathway, and other signaling pathways related to reproduction, such as SOCS3. Furthermore, the central proteins POSTN, MFAP5, and DCN from protein–protein interaction may regulate animal reproductive activity by affecting cell proliferation and apoptosis. lncRNA MSTRG.33887.2 as well as circRNAs chicirc_098002, chicirc_072583, and chicirc_053531 may be able to influence animal reproduction by participating in folate metabolism and energy metabolism homeostasis through their respective target genes. Our results expand the molecular mechanism of hypothalamic regulation on animal reproduction.

As an important organ that coordinates the neuroendocrine system, the hypothalamus synthesizes and secretes reproductive hormones that act on the goat organism, thereby precisely regulating follicular development and reproductive processes in goats. However, it is still elusive to explore the mechanism of hypothalamic effects on goat fertility alone. Therefore, RNA-seq was used to analyze the gene expression in hypothalamic tissues of goats in high fertility group (HFG: litter size per litter ≥2) and low fertility group (LFG: litter size per litter = 1), and identified the differential lncRNAs and mRNAs and their associated pathways related to their fertility. The results showed that a total of 23 lncRNAs and 57 mRNAs were differentially expressed in the hypothalamic tissue of high and low fertility goats. GO terms and KEGG functional annotation suggest that DE lncRNAs and DE mRNAs were significantly enriched in hormone-related pathways regulating ovarian development, hormone synthesis and secretion, regulation of reproductive processes, Estrogen signaling pathway, Oxytocin signaling pathway and GnRH signaling pathway. And we constructed a co-expression network of lncRNAs and target genes, and identified reproduction-related genes such as NMUR2, FEZF1, and WT1. The sequencing results of the hypothalamic transcriptome have broadened our understanding of lncRNA and mRNA in goat hypothalamic tissue and provided some new insights into the molecular mechanisms of follicle development and regulation of its fertility in goats.