Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
J Cell Physiol. 2019 Aug;234(10):18666-18678. doi: 10.1002/jcp.28505. Epub 2019 Mar 29.
In ruminant, adequate endometrial function is a major factor affecting implantation and economic efficiency. However, the precise mechanisms regulating goat endometrial function during the peri-implantation period of pregnancy are still unclear. Here, we investigated the functional role and signal transduction of the fifth component of the constitutive photomorphogenic-9 signalosome (COPS5) in the regulation of endometrial function in endometrial epithelial cells (EECs). Our results showed that hormones decreased COPS5 expression, and COPS5-mediated regulation of endometrial function. We also found that knockdown of COPS5 hindered EECs proliferation by the G1-phase cell cycle arrest. Hormones affected the activity of COPS5 through hormones receptors, while feedback from the expression of COPS5 regulated the transcription of the receptor. Moreover, knockdown of endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) via si-ERN1 partly inhibited endometrial function in shCOPS5 EECs. In addition, blocking the mTOR pathway by rapamycin promoted endometrial function in si-ERN1-transfected shCOPS5 EECs. Overall, these results suggest that COPS5 negatively regulates goat endometrial function via the ERN1 and mTOR-autophagy pathways and provide new insights into the mechanistic pathways of COPS5 during female reproductive development.
在反刍动物中，充分的子宫内膜功能是影响着床和经济效益的主要因素。然而，在妊娠着床期间调节山羊子宫内膜功能的确切机制仍不清楚。在这里，我们研究了组成型光形态发生 9 信号体的第五个成分（COPS5）在调节子宫内膜上皮细胞（EEC）子宫内膜功能中的功能作用和信号转导。我们的结果表明，激素降低了 COPS5 的表达，并调节了子宫内膜功能。我们还发现，COPS5 的敲低通过 G1 期细胞周期阻滞阻碍了 EEC 的增殖。激素通过激素受体影响 COPS5 的活性，而 COPS5 表达的反馈调节受体的转录。此外，通过 si-ERN1 敲低内质网到核信号 1（ERN1）部分抑制了 shCOPS5 EECs 的子宫内膜功能。此外，通过雷帕霉素阻断 mTOR 通路促进了 si-ERN1 转染的 shCOPS5 EECs 中的子宫内膜功能。总的来说，这些结果表明，COPS5 通过 ERN1 和 mTOR-自噬途径负调节山羊子宫内膜功能，并为女性生殖发育过程中 COPS5 的机制途径提供了新的见解。
