PMID- 36423098 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221128 IS - 2306-7381 (Electronic) IS - 2306-7381 (Linking) VI - 9 IP - 11 DP - 2022 Nov 21 TI - PPARgamma/mTOR Regulates the Synthesis and Release of Prostaglandins in Ovine Trophoblast Cells in Early Pregnancy. LID - 10.3390/vetsci9110649 [doi] LID - 649 AB - Trophoblast cells synthesize and secrete prostaglandins (PGs), which are essential for ruminants in early gestation to recognize pregnancy. Hormones in the intrauterine environment play an important role in regulating PGs synthesis during implantation, but the underlying mechanism remains unclear. In this study, co-treatment of sheep trophoblast cells (STCs) with progesterone (P(4)), estradiol (E(2)), and interferon-tau (IFN-tau) increased the ratio of prostaglandin E2 (PGE(2)) to prostaglandin F2alpha (PGF(2alpha)) and upregulated peroxisome proliferator-activated receptor gamma (PPARgamma) expression, while inhibiting the mechanistic target of rapamycin (mTOR) pathway and activating cellular autophagy. Under hormone treatment, inhibition of PPARgamma activity decreased the ratio of PGE(2)/PGF2alpha and cellular activity, while activating expression of the mTOR downstream marker-the phosphorylation of p70S6K (p-p70S6K). We also found that the PPARgamma/mTOR pathway played an important role in regulating trophoblast cell function. Inhibition of the mTOR pathway by rapamycin increased the ratio of PGE(2)/PGF(2alpha) and decreased the expression of apoptosis-related proteins after inhibiting PPARgamma activity. In conclusion, our findings provide new insights into the molecular mechanism of prostaglandin regulation of trophoblast cells in sheep during early pregnancy, indicating that the PPARgamma/mTOR pathway plays an important role in PGs secretion and cell viability. FAU - Hao, Kexing AU - Hao K AD - College of Animal Science and Technology, Shihezi University, Shihezi 832000, China. FAU - Wang, Jing AU - Wang J AD - College of Animal Science and Technology, Shihezi University, Shihezi 832000, China. FAU - Li, Zhiyuan AU - Li Z AD - College of Animal Science and Technology, Shihezi University, Shihezi 832000, China. FAU - Chen, Huihui AU - Chen H AD - College of Animal Science and Technology, Shihezi University, Shihezi 832000, China. FAU - Jia, Bin AU - Jia B AD - College of Animal Science and Technology, Shihezi University, Shihezi 832000, China. FAU - Hu, Guangdong AU - Hu G AD - College of Animal Science and Technology, Shihezi University, Shihezi 832000, China. LA - eng GR - 32060751/National Natural Science Foundation of China/ GR - 32160833/National Natural Science Foundation of China/ GR - MYSKLKF201905/Open Project of State Key Laboratory of Sheep Genetic Improvement and Healthy Production/ GR - 2020BTDJ05/Open Project of Key Laboratory of Animal Disease Prevention and Control Corps/ PT - Journal Article DEP - 20221121 PL - Switzerland TA - Vet Sci JT - Veterinary sciences JID - 101680127 PMC - PMC9694237 OTO - NOTNLM OT - PGE2/PGF2alpha OT - PPARgamma OT - mTOR OT - prostaglandins OT - trophoblast cells COIS- The authors declare no conflict of interest. EDAT- 2022/11/25 06:00 MHDA- 2022/11/25 06:01 PMCR- 2022/11/21 CRDT- 2022/11/24 12:03 PHST- 2022/10/12 00:00 [received] PHST- 2022/11/04 00:00 [revised] PHST- 2022/11/17 00:00 [accepted] PHST- 2022/11/24 12:03 [entrez] PHST- 2022/11/25 06:00 [pubmed] PHST- 2022/11/25 06:01 [medline] PHST- 2022/11/21 00:00 [pmc-release] AID - vetsci9110649 [pii] AID - vetsci-09-00649 [pii] AID - 10.3390/vetsci9110649 [doi] PST - epublish SO - Vet Sci. 2022 Nov 21;9(11):649. doi: 10.3390/vetsci9110649.