The Effect and Mechanism of Asymmetric Dimethylarginine Regulating Trophoblastic Autophagy on Fetal Growth Restriction.

Fetal growth restriction (FGR) is an important cause of perinatal death and adverse pregnancy outcomes. Asymmetric dimethylarginine (ADMA) is associated with FGR, but the mechanisms have not been thoroughly studied. Here, we determined the levels of ADMA and autophagy-related molecules in human blood samples and placental tissues. And we also used the human chorionic carcinoma cell line BeWo to investigate the mechanism of ADMA-induced FGR in vitro. Compared with the control group, ADMA levels in maternal blood and placenta were increased in patients with FGR, and the birth weight (BW) percentile was negatively correlated with maternal serum ADMA concentration in the FGR group. The expression of mammalian target of rapamycin (mTOR) in the placenta of the FGR group was lower than the control group, while the expression of Beclin-1 and microtubule-associated protein 1 light chain 3-II (LC3-II)/LC3-I was significantly increased in the FGR group. And the expression of matrix metalloproteinase 9 (MMP9) was decreased in the placenta of patients with FGR. In in vitro cell experiments, compared with the control group, the expression of mTOR and MMP9 in BeWo cells was decreased and the expression of Beclin-1 and LC3-II/LC3-I was increased in the ADMA-treated group. Moreover, ADMA had favorable effects on the formation of autophagic vacuoles, and the autophagy inhibitor 3-Methyladenine (3-MA) could reduce the autophagy-induction effect of ADMA on BeWo cells. This study found that ADMA could participate in the occurrence of FGR through inducing autophagy in trophoblasts.