Placental Transport of Amino Acids in Rats with Methionine-Induced Hyperhomocysteinemia

被引:0
|
作者
Milyutina, Yulia P. [1 ]
Kerkeshko, Gleb O. [1 ]
Vasilev, Dmitrii S. [1 ,2 ]
Zalozniaia, Irina V. [1 ]
Bochkovskii, Sergey K. [1 ]
Tumanova, Natalia L. [2 ]
Shcherbitskaia, Anastasiia D. [1 ]
Mikhel, Anastasiia V. [1 ]
Tolibova, Gulrukhsor H. [1 ]
Arutjunyan, Alexander V. [1 ]
机构
[1] D O Ott Res Inst Obstet Gynecol & Reprod Med, St Petersburg 199034, Russia
[2] Russian Acad Sci, I M Sechenov Inst Evolutionary Physiol & Biochem, St Petersburg 194223, Russia
基金
俄罗斯科学基金会;
关键词
maternal hyperhomocysteinemia; placenta; placental transport; placental barrier; amino acids; mTOR; amino acid transporters; SYNTHASE-DEFICIENT MICE; NUTRIENT TRANSPORTERS; PLASMA HOMOCYSTEINE; MATERNAL OBESITY; MOUSE PLACENTA; GROWTH-FACTORS; ANIMAL-MODEL; FETAL; MTORC1; SUPPLEMENTATION;
D O I
10.1134/S0006297924100055
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
AbstractMaternal hyperhomocysteinemia (HHcy) is a risk factor for intrauterine growth restriction presumably caused by a decrease in the placental transport of nutrients. We investigated the effect of experimental HHcy induced by daily methionine administration to pregnant rats on the free amino acid levels in the maternal and fetal blood, as well as on morphological and biochemical parameters associated with the amino acid transport through the placenta. HHcy caused an increase in the levels of most free amino acids in the maternal blood on gestational day 20, while the levels of some amino acids in the fetal blood were decreased. In rats with HHcy, the maternal sinusoids in the placental labyrinth were narrowed, which was accompanied by aggregation of red blood cells. We also observed an increase in the neutral amino acid transporters (LAT1, SNAT2) protein levels and activation of 4E-BP1, a downstream effector of mTORC1 complex, in the labyrinth zone. Maternal HHcy affected the placental barrier permeability, as evidenced by intensification of the mother-to-fetus transfer of Evans Blue dye. The imbalance in the free amino acid levels in the maternal and fetal blood in HHcy may be due to the competition of homocysteine with other amino acids for common transporters, as well as a decrease in the area of exchange zone between maternal and fetal circulations in the placental labyrinth. Upregulation of the neutral amino acid transporter expression in the labyrinth zone may be a compensatory response to an insufficient intrauterine amino acid supply and fetal growth restriction.
引用
收藏
页码:1711 / 1726
页数:16
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