miR-27a-3p targets NR5A2 to regulate CYP19A1 expression and 17-β estradiol synthesis in ovine granulosa cells

• Published in: Animal reproduction science 2023-01, Vol.248, p.107160-107160, Article 107160
• Main Authors: Gui, Hongbing, Li, Fan, Chen, Cheng, Zhu, Qiuyi, Zhang, Chenjian, Zhang, Jun, Meng, Chunhua, Qian, Yong, Cao, Shaoxian, Li, Yinxia
• Format: Article
• Language: English
• Subjects: Animals; Estradiol - metabolism; Estradiol synthesis; Female; Granulosa cells; Granulosa Cells - metabolism; Hu sheep; Mammals; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-27a-3p; NR5A2; Receptors, Cytoplasmic and Nuclear - metabolism; Sheep - genetics
• ISSN: 0378-4320; 1873-2232
• DOI: 10.1016/j.anireprosci.2022.107160

Although 17-β estradiol (E2) synthesis is important in regulating female fertility, we know little regarding the molecular mechanism of miRNA-regulated ovine E2 synthesis. Here, our experiments with granulosa cells (GCs) from Hu sheep revealed miR-27a-3p involvement in E2 synthesis and its association with ovine litter size. First, we showed that miR-27a-3p of sheep and other mammals share a high nucleotide identity. Next, gain- and loss-of-function assays indicated that miR-27a-3p inhibits CYP19A1 expression and E2 synthesis in GCs. Moreover, we demonstrated that NR5A2 is a direct target of miR-27a-3p. Ovine miR-27a-3p suppresses E2 synthesis via the NR5A2 and CYP19A1 axes. We also identified four single nucleotide polymorphisms in the ovine miR-27a gene, and g.–13 G>A and g 0.24 T > G were significantly associated with the first and the second parity litter size, respectively (P