Cortisol promotes placental glucose and amino acids transport by activating the mechanistic target of rapamycin complex 1 signaling pathway.

Low birth weight (LBW) has been an important problem in animal husbandry, contributing to high mortality and morbidity rates in the neonatal period. To explore the mechanism regulating placental function and fetal development, paired normal birth weight (NBW, 1.54 ± 0.08 kg) and LBW (0.95 ± 0.16 kg) piglets (n = 10) were selected from ten gilts. Serum biochemistry indexes and placental transport capacity were measured. Placental and serum samples of sows or piglets were collected, and the characteristics of sows and piglets were recorded. Furthermore, this study utilized porcine trophoblast cells (pTrs) as a model to investigate the effects of cortisol (0, 0.01, 0.1, and  pg/mL) on cell viability, migration, glucose transport, gene and protein expression. Additionally, rapamycin (20 nmol/L) was used to inhibit the activity of mammalian target of rapamycin complex 1 (mTORC1). All experiments were independently repeated at least three times. Data were analyzed using SAS (version 9.4). An unpaired t-test was applied to compare values between the LBW and NBW piglets. Student's t-tests were used for single comparisons in cell experiments. Significance was declared at P < 0.05. Results showed that LBW piglets had reduced levels of glucose, cortisol, Phe, Val, Ile, Leu, Met, and homocysteine compared to NBW piglets (P < 0.05). Moreover, the placental expression of Glut1 and Slc43a2 were significantly downregulated (P < 0.05), and mTORC1 signaling pathway was inhibited (P < 0.05) in LBW piglets compared with NBW piglets. Furthermore, birth weight of piglets was positively correlated with cortisol levels (P < 0.01, r = 0.58). Further results found that cortisol activated the protein expression of p-S6K1 (P < 0.05) and upregulated the protein expression of GLUT3, LAT2, and SLC6A19 (P < 0.05), and increased the glucose transport rate and number of cell migrations (P < 0.05). However, rapamycin supplementation downregulated the protein expression of p-S6K1 (P < 0.05) and reduced the number of cell migration (P < 0.05) in the cortisol group. Overall, these results suggest that cortisol improves the placental glucose and amino acid transport via the mTORC1 signaling pathway.