Zhang Lei, Liu Xiaorui, Liu Junze, Zhou Zhanqin, Song Yuxuan, Cao Binyun, An Xiaopeng
College of Animal Science and Technology, Northwest Agriculture and Forestry University, Yangling, Shaanxi, China.
PLoS One. 2017 Jul 5;12(7):e0179783. doi: 10.1371/journal.pone.0179783. eCollection 2017.
Increasing evidence has shown that miRNAs play important roles in endometrium development during the menstrual cycle in humans and many other animals. Our previous data indicated that miR-182 levels increase 15.55-fold and pleiotrophin (PTN) levels decrease 20.97-fold in the receptive endometrium (RE, D15) compared with the pre-receptive endometrium (PE, D5) in dairy goats. The present study shows that miR-182 is widely expressed in different tissues of dairy goats and that its expression levels are regulated by E2 and P4 in endometrial epithelium cells (EECs). We confirmed that PTN is a target of miR-182 and that miR-182 regulates the protein levels of AKT, Bcl-2, FAS, MAPK, Caspase-3 and SP1 in EECs. Furthermore, miR-182 up-regulates or maintains the expression levels of osteopontin (OPN), cyclooxygenase-2 (COX-2) and prolactin receptor (PRLR) in EECs, suggesting that miR-182 is an important regulatory factor in the construction of endometrial receptivity in dairy goats. In conclusion, miR-182 participates in the development of endometrial receptivity by down-regulating PTN and affecting the expression of select apoptosis-related genes and increasing or maintaining the expression levels of OPN, COX-2 and PRLR in the EECs of dairy goats.
越来越多的证据表明,微小RNA(miRNAs)在人类和许多其他动物月经周期的子宫内膜发育过程中发挥着重要作用。我们之前的数据表明,与奶山羊的非接受性子宫内膜(PE,D5)相比,接受性子宫内膜(RE,D15)中miR-182水平增加了15.55倍,多效生长因子(PTN)水平降低了20.97倍。本研究表明,miR-182在奶山羊的不同组织中广泛表达,其表达水平受子宫内膜上皮细胞(EECs)中雌二醇(E2)和孕酮(P4)的调节。我们证实PTN是miR-182的靶标,并且miR-182调节EECs中AKT、Bcl-2、FAS、丝裂原活化蛋白激酶(MAPK)、半胱天冬酶-3(Caspase-3)和特异性蛋白1(SP1)的蛋白水平。此外,miR-182上调或维持EECs中骨桥蛋白(OPN)、环氧合酶-2(COX-2)和催乳素受体(PRLR)的表达水平,这表明miR-182是奶山羊子宫内膜接受性构建中的一个重要调节因子。总之,miR-182通过下调PTN、影响某些凋亡相关基因的表达以及增加或维持奶山羊EECs中OPN、COX-2和PRLR的表达水平来参与子宫内膜接受性的发育。