Abstract：
Follicular cysts are a common reproductive disorder in domestic animals that cause considerable economic losses to the farming industry. Effective prevention and treatment methods are lacking because neither the pathogenesis nor formation mechanisms of follicular cysts are well-understood. In this study, we first investigated the granulosa cells (GCs) of cystic follicles isolated from pigs. We observed a significant reduction in the expression of methyltransferase-like 3 (METTL3). Subsequent experiments revealed that METTL3 downregulation in GCs caused a decrease in m6A modification of pri-miR-21. This reduction further inhibited DGCR8 recognition and binding to pri-miR-21, dampening the synthesis of mature miR-21-5p. Additionally, the decrease in miR-21-5p promotes IL-1β expression in GCs. Elevated IL-1β activates the NFκB pathway, in turn upregulating apoptotic genes TNFa and BAX/BCL2. The subsequent apoptosis of GCs and inhibition of autophagy causes downregulation of CYP19A1 expression. These processes lower oestrogen secretion and contribute to follicular cyst formation. In conclusion, our findings provide a foundation for understanding and further exploring the mechanisms of follicular-cyst development in farm animals. This work has important implications for treating ovarian disorders in livestock and could potentially be extended to humans.
摘要：
卵泡囊肿是家畜中常见的生殖疾病，对养殖业造成相当大的经济损失。缺乏有效的预防和治疗方法，因为对卵泡囊肿的发病机理和形成机制都没有很好的了解。在这项研究中,我们首先研究了从猪中分离的囊性卵泡的颗粒细胞（GC）。我们观察到甲基转移酶样3(METTL3)的表达显著降低。随后的实验显示,GC中的METTL3下调导致pri-miR-21的m6A修饰减少。这种减少进一步抑制DGCR8识别和与pri-miR-21的结合,抑制成熟miR-21-5p的合成。此外,miR-21-5p的减少促进了GC中IL-1β的表达。升高的IL-1β激活NFκB途径，进而上调凋亡基因TNFa和BAX/BCL2。随后GCs的凋亡和自噬的抑制导致CYP19A1表达下调。这些过程降低了雌激素的分泌，并有助于卵泡囊肿的形成。总之,我们的发现为理解和进一步探索农场动物卵泡囊肿发育的机制提供了基础。这项工作对治疗牲畜卵巢疾病具有重要意义，并可能扩展到人类。
