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

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

Journal

Biochemistry (Moscow)
ISSN: 0006-2979 , E-ISSN: 1608-3040

Output data

Year: 2024, Volume: 89, Number: 10, Pages: 1711-1726 Pages count : 16 DOI: 10.1134/S0006297924100055

Tags

amino acid transporters; amino acids; mTOR; maternal hyperhomocysteinemia; placenta; placental barrier; placental transport

Authors

Milyutina Y.P. ¹ , Kerkeshko G.O. ¹ , Vasilev D.S. ^1,2 , Zalozniaia I.V. ¹ , Bochkovskii S.K. ¹ , Tumanova N.L. ² , Shcherbitskaia A.D. ¹ , Mikhel A.V. ¹ , Tolibova G.H. ¹ , Arutjunyan A.V. ¹

Affiliations

1	D. O. Ott Research Institute of Obstetrics, Gynecology, and Reproductive Medicine, St. Petersburg, 199034, Russia
2	I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, 194223, Russia

Maternal 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.

Milyutina Y.P. , Kerkeshko G.O. , Vasilev D.S. , Zalozniaia I.V. , Bochkovskii S.K. , Tumanova N.L. , Shcherbitskaia A.D. , Mikhel A.V. , Tolibova G.H. , Arutjunyan A.V.
Placental Transport of Amino Acids in Rats with Methionine-Induced Hyperhomocysteinemia
Biochemistry (Moscow). 2024. V.89. N10. P.1711-1726. DOI: 10.1134/S0006297924100055 WOS OpenAlex

Submitted:	Dec 2, 2023
Accepted:	May 2, 2024
Published print:	Nov 8, 2024
Published online:	Nov 8, 2024

Web of science:	WOS:001352312400003
OpenAlex:	W4404174498

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