Altered expression of mTOR and autophagy in term normal human placentas.

Mammalian target of rapamycin (mTOR) and autophagy have been implied in trophoblast cells proliferation and invasion. This study investigated whether mTOR and autophagy were involved in placental development and fetal programming. A total of 90 term normal placentas (37-42 gestational weeks) were collected from women who underwent elective cesarean section, with large for gestational age (LGA), fetal growth restriction (FGR), and appropriate for gestational age (AGA) infants (n=30, respectively). Capillary volume density within peripheral villi significantly decreased in the FGR placentas compared with the AGA group (p<0.01). Autophagic vacuoles were more prominent in the FGR placentas than in the AGA pregnancies (p<0.001). LC3B-II and Beclin1 in placentas of FGR were increased by 99% and 83%, respectively, while p62 was descended by 39% (p<0.001), compared with that in the AGA group. Whereas, there was no significant differences in these autophagy-related proteins between the LGA and AGA pregnancies. Compared to the AGA pregnancies, placental mTOR was reduced by 30% in the FGR group and raised by 26% in the LGA group (p<0.05). Pearson's correlation analysis showed a significantly inverse correlation between mTOR level and LC3B-II expression (r=-0.456, p<0.01), as well as between mTOR and Beclin1 expression in term human placentas (r=-0.468, p<0.01). These results demonstrate that altered expression of mTOR and autophagy may be associated with the development of placentas and pathophysiology of FGR, and that there may be a reciprocal regulation between mTOR and autophagy in human placentas.