INHA, the gene encoding the inhibin alpha subunit, was involved in folliculogenesis in mammals, but no study was reported for its working pathway in birds. Here we hypothesize that gene polymorphism in INHA 3'UTR might influence miRNAs binding efficiency and further affect the function of this gene. Thus, we investigated the association between the 3'UTR single-nucleotide polymorphisms (SNPs) in INHA and the laying performance in chickens and further explore their possible molecular cascades in granulosa cells (GC). Five SNPs were detected in Tianfu green-shell layers and g. 22,178,975 G > A was significantly associated with total egg numbers at the age of 300 days (EN, n = 286). Birds carrying the AA genotype laid more EN than those with GG (P < 0.05). The allele transition from G to A in the 3'UTR of INHA gene destroyed a binding site which was targeted by miR-181b-1-3p. The expression abundances of INHA mRNA increased firstly and then decreased with follicle growing, and reached the top in the sixth largest pre-ovulation follicle, whereas miR-181b-1-3p levels in chicken pre-hierarchical follicles had the contrary tendency. Further studies indicated that high levels of miR-181b-1-3p increased apoptosis and reduced GC proliferation while miR-181b-1-3p inhibitors decreased apoptosis and promoted GC proliferation. Additionally, depression of INHA increased apoptosis and reduced GC proliferation via a caspase-3-dependent mitochondrial pathway. Generally, the mutation in INHA 3'UTR was tightly correlated with egg production in chickens, and blocked a binding site of miR-181b-1-3p. miR-181b-1-3p inhibited GC proliferation and promoted apoptosis by targeting INHA.

中文翻译：

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miR-181b-1-3p结合位点抑制素α亚基功能多态性调控鸡卵巢颗粒细胞增殖和凋亡

INHA 是编码抑制素 α 亚基的基因，参与哺乳动物的卵泡发生，但没有研究报告其在鸟类中的工作途径。在这里，我们假设 INHA 3'UTR 中的基因多态性可能会影响 miRNA 的结合效率并进一步影响该基因的功能。因此，我们研究了 INHA 中 3'UTR 单核苷酸多态性 (SNP) 与鸡的产蛋性能之间的关联，并进一步探索它们在颗粒细胞 (GC) 中可能的分子级联反应。在天府绿壳层和 g. 中检测到 5 个 SNP。22,178,975 G > A 与 300 日龄时的总卵数显着相关（EN，n = 286）。携带 AA 基因型的家禽比携带 GG 的家禽产下更多的 EN（P < 0.05）。在 3' 中从 G 到 A 的等位基因转变 INHA 基因的 UTR 破坏了 miR-181b-1-3p 靶向的结合位点。INHA mRNA的表达丰度随着卵泡的生长呈先升高后降低的趋势，在排卵前第六大卵泡中达到最高，而鸡分级前卵泡中的miR-181b-1-3p水平则相反。进一步的研究表明，高水平的 miR-181b-1-3p 增加细胞凋亡并减少 GC 增殖，而 miR-181b-1-3p 抑制剂减少细胞凋亡并促进 GC 增殖。此外，抑制 INHA 通过依赖 caspase-3 的线粒体途径增加细胞凋亡并减少 GC 增殖。一般来说，INHA 3'UTR 的突变与鸡的产蛋量密切相关，并阻断了 miR-181b-1-3p 的结合位点。