State Key Laboratory of Swine and Poultry Breeding Industry, Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, and Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.
Animal Breeding and Genetics Key Laboratory of Sichuan Province, Sichuan Animal Science Academy, Chengdu, China.
Theriogenology. 2024 Jan 15;214:370-385. doi: 10.1016/j.theriogenology.2023.11.007. Epub 2023 Nov 17.
Steroid hormones play a crucial role in the growth and maturation of poultry ovarian follicles, with progesterone secretion by granulosa cells (GC) being essential. According to our previous transcriptome analysis, it apparented that miR-146a-5p expressions were upregulated in the follicles undergoing atresia. In this study, we delved the depth to explore the underlying mechanisms by miR-146a-5p in the regulation of follicle functions in chicken. The study demonstrated that miR-146a-5p suppressed cell growth, lipids accumulation, and progesterone biosynthesis in chicken GC. Through targeting association validations, we identified delta 4-desaturase, sphingolipid 1 (DEGS1) as capable of interacting with miR-146a-5p. Co-transfection experiments further confirmed that DEGS1 reversed the impairment of GC functions by miR-146a-5p. Moreover, we discovered that miR-146a-5p suppressed AKT phosphorylation, while DEGS1 enhanced AKT phosphorylation. Phosphatidylinositol-3 kinase (PI3K) inhibitor (LY294002) studies showed that miR-146a-5p would inhibit AKT phosphorylation by governing the DEGS1/AKT pathway, which in turn regulates GC function. In summary, the findings revealed that miR-146a-5p suppressed cell growth, lipid deposition, and progesterone biosynthesis via the DEGS1/AKT pathway. These results may further enrich our understandings of how non-coding RNA regulates productive performance in chickens.
甾体激素在禽类卵巢卵泡的生长和成熟中起着至关重要的作用，其中颗粒细胞（GC）分泌的孕激素是必不可少的。根据我们之前的转录组分析，miR-146a-5p 在正在发生闭锁的卵泡中表达上调。在这项研究中，我们深入探讨了 miR-146a-5p 调节鸡卵泡功能的潜在机制。研究表明，miR-146a-5p 抑制鸡 GC 的细胞生长、脂质积累和孕激素生物合成。通过靶基因关联验证，我们确定 delta 4-去饱和酶 1（DEGS1）能够与 miR-146a-5p 相互作用。共转染实验进一步证实，DEGS1 逆转了 miR-146a-5p 对 GC 功能的损伤。此外，我们发现 miR-146a-5p 抑制 AKT 磷酸化，而 DEGS1 增强 AKT 磷酸化。PI3K 抑制剂（LY294002）研究表明，miR-146a-5p 通过调控 DEGS1/AKT 通路抑制 AKT 磷酸化，从而调节 GC 功能。综上所述，这些发现表明，miR-146a-5p 通过 DEGS1/AKT 通路抑制细胞生长、脂质沉积和孕激素生物合成。这些结果可能进一步丰富我们对非编码 RNA 如何调节鸡产蛋性能的理解。
