1. Academic Validation
  2. LncRNA STAT3-AS regulates endometrial receptivity via the STAT3 signaling pathway

LncRNA STAT3-AS regulates endometrial receptivity via the STAT3 signaling pathway

  • Theriogenology. 2023 Dec 29:216:118-126. doi: 10.1016/j.theriogenology.2023.12.032.
Yanni Jia 1 Wei Wang 2 Jiaqi Jiang 1 Xinyan Zhang 1 Haijing Li 1 Suhua Gong 1 Zuhui Li 1 Haokun Liu 1 Chunmei Shang 1 Aihua Wang 1 Yaping Jin 3 Pengfei Lin 4
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, China.
  • 2 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
  • 3 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: [email protected].
  • 4 College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China; Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi, China. Electronic address: [email protected].
Abstract

Endometrial receptivity is critical for the successful establishment of pregnancy in ruminants. Interferon tau (IFNT) plays a key role in promoting embryo attachment by activating the Janus kinase/signal transducer and activator of transcription pathway, which induces the expression of a series of interferon-stimulated genes (ISGs). In our previous study, sequencing analysis of goat endometrial epithelial cells (gEECs) treated with 20 ng/mL IFNT revealed a differentially expressed long non-coding RNA located on the STAT3 antisense chain, which we designated STAT3-AS. The aim of this study was to investigate the role and mechanism of STAT3-AS in establishing endometrial receptivity in goats. The results showed that STAT3-AS was expressed in both the nucleus and cytoplasm of gEECs, and its expression increased significantly in the uterus on day 15 of pregnancy. STAT3-AS expression was upregulated in gEECs treated with IFNT alone or in combination with progesterone and estradiol. Knockdown of STAT3-AS using specific short interfering RNA significantly inhibited the expression of classical ISGs such as interferon-stimulated gene 15 and 2',5'-oligodenylate synthetase 2, as well as uterine endometrial receptivity-related genes including homeobox gene A11, Integrin beta 3, and vascular endothelial growth factor. Moreover, gEEC proliferation and the STAT3 pathway were suppressed in the absence of STAT3-AS. However, pretreatment with the STAT3 Activator RO8191 restored the effect of silencing STAT3-AS on endometrial receptivity. Overall, these results suggest that STAT3-AS is an important regulator of endometrial receptivity in goats and that it regulates endometrial receptivity through the STAT3 pathway.

Keywords

Embryo implantation; Goat; Interferon tau; STAT3; STAT3-AS.

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