PPARγ/mTOR Regulates the Synthesis and Release of Prostaglandins in Ovine Trophoblast Cells in Early Pregnancy

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 F2 alpha (PGF(2 alpha)) and upregulated peroxisome proliferator-activated receptor gamma (PPAR gamma) expression, while inhibiting the mechanistic target of rapamycin (mTOR) pathway and activating cellular autophagy. Under hormone treatment, inhibition of PPAR gamma activity decreased the ratio of PGE(2)/PGF2 alpha and cellular activity, while activating expression of the mTOR downstream marker-the phosphorylation of p70S6K (p-p70S6K). We also found that the PPAR gamma/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(2 alpha) and decreased the expression of apoptosis-related proteins after inhibiting PPAR gamma 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 PPAR gamma/mTOR pathway plays an important role in PGs secretion and cell viability.