Table_2_Novel Regulatory Factors in the Hypothalamic-Pituitary-Ovarian Axis of Hens at Four Developmental Stages.DOCX

Ovarian follicular development is an extremely complex and precise process in which the hypothalamic-pituitary-ovarian (HPO) axis plays a crucial role. However, research on the regulatory factors of the HPO axis is sparse. In this study, transcriptomes of the tissues in the entire HPO axis at 15, 20, 30, and 68 w of age were analyzed. In total, 381, 622, and 1090 differentially expressed genes (DEGs) were found among the hypothalamus, pituitary, and ovary, respectively. In particular, the greatest number of DEGs (867) was identified from the comparison of ovary at 30 and 15 w, which might be related to ovarian development and function at high ovulation capacity. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that most of these DEGs in the significantly enriched biological process (BP) terms and pathways were primarily involved in tissue development and the regulation of reproductive hormone biosynthesis and secretion. The latter is highly related to the HPO axis. Therefore, a number of hub candidate genes strongly associated with the HPO axis in each tissue were filtered by analyzing the Protein-protein interaction (PPI) network and seven known reproductive hormone-associated key genes were obtained: PGR, HSD3B2, CYP17A1, CYP11A1, CYP21A2, STS, and CYP19A1, and 12 novel genes: ROCK2, TBP, GTF2H2, GTF2B, DHCR24, DHCR7, FDFT1, LSS, SQLE, MSMO1, CYP51A1, and PANK3. These will be utilized for further research into the function of the HPO axis. This study has highlighted the major role of the HPO axis in the reproduction of hens at the four developmental stages and explored the novel factors that might regulate reproduction, thus providing new insights into the function of the HPO axis on the reproductive system.

卵巢卵泡发育是一个极为复杂且精细的生物学过程，下丘脑-垂体-卵巢（hypothalamic-pituitary-ovarian, HPO）轴在此过程中发挥关键调控作用。然而目前针对HPO轴调控因子的相关研究仍较为匮乏。本研究针对15、20、30及68周龄母鸡全HPO轴各组织的转录组进行了分析。最终分别在下丘脑、垂体与卵巢组织中鉴定出381、622及1090个差异表达基因（differentially expressed genes, DEGs）。尤为值得注意的是，在30周龄与15周龄卵巢组织的对比分析中，鉴定出的DEGs数量最多，达867个，这或与高排卵能力阶段的卵巢发育及功能密切相关。基因本体论（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析结果显示，在显著富集的生物过程（biological process, BP）术语及通路中，绝大多数DEGs主要参与组织发育以及生殖激素的生物合成与分泌调控。上述生殖激素调控过程与HPO轴的关联极为紧密。因此，本研究通过构建蛋白质相互作用（protein-protein interaction, PPI）网络，筛选出各组织中与HPO轴强相关的核心候选基因，共得到7个已报道的生殖激素相关关键基因：PGR、HSD3B2、CYP17A1、CYP11A1、CYP21A2、STS及CYP19A1，以及12个新发现的候选基因：ROCK2、TBP、GTF2H2、GTF2B、DHCR24、DHCR7、FDFT1、LSS、SQLE、MSMO1、CYP51A1及PANK3。上述基因可用于后续HPO轴功能的相关研究。本研究明确了HPO轴在4个发育阶段母鸡繁殖过程中的核心调控作用，同时发掘了潜在的生殖调控新因子，为解析HPO轴在生殖系统中的功能提供了全新的研究视角。