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Neurotrophins of the Fetal Brain and Placenta in Prenatal Hyperhomocysteinemia

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Abstract

Prenatal hyperhomocysteinemia (PHHC) in pregnant rats was induced by chronic L-methionine loading, resulting in a significant increase in the L-homocysteine content both in the mothers’ blood and blood and brain of fetuses. Significant decrease in the weight of the placenta, fetus, and fetal brain was detected by the morphometric studies on day 20 of pregnancy. PHHC also activated maternal immune system due to the increase in the content of proinflammatory inter-leukin-1β in the rat blood and fetal part of the placenta. PHHC elevated the levels of the brain-derived neurotrophic factor (BDNF, 29 kDa) and nerve growth factor (NGF, 31 kDa) precursors in the placenta and the content of the BDNF isoform (29 kDa) in the fetal brain. The content of neuregulin 1 (NRG1) decreased in the placenta and increased in the fetal brain on day 20 of embryonic development. An increase in the caspase-3 activity was detected in the brains of fetuses subjected to PHHC. It was suggested that changes in the processing of neurotrophins induced by PPHC, oxidative stress, and inflammatory processes initiated by it, as well as apoptosis, play an important role in the development of brain disorders in the offspring.

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Abbreviations

FPP:

fetal part of placenta

HC:

homocysteine

HHC:

hyperhomocysteinemia

IL-1β:

interleukin-1β

IL-6:

inter-leukin-6

MPP:

maternal part of placenta

NGF:

nerve growth factor

NRG1:

neuregulin 1

p75NTR:

p75 neurotrophin receptor

PHHC:

prenatal hyperhomocysteinemia

ROS:

reactive oxygen species

TNF-α:

tumor necrosis factor α

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Funding

This work was supported by the Russian Foundation for Basic Research (project 18-015-00099) and by the State Budget Project no. AAAA-A19-119021290116-1.

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Authors and Affiliations

  1. Ott Institute of Obstetrics, Gynecology, and Reproductology, 199034, St. Petersburg, Russia

    A. V. Arutjunyan, Yu. P. Milyutina, G. O. Kerkeshko, I. V. Zalozniaia & A. V. Mikhel

  2. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St. Petersburg, Russia

    A. D. Shcherbitskaia

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  1. A. V. Arutjunyan
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Correspondence to A. V. Arutjunyan.

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Russian Text © The Author(s), 2020, published in Biokhimiya, 2020, Vol. 85, No. 2, pp. 248-259.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM19-137, December 16, 2019.

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Arutjunyan, A.V., Milyutina, Y.P., Shcherbitskaia, A.D. et al. Neurotrophins of the Fetal Brain and Placenta in Prenatal Hyperhomocysteinemia. Biochemistry Moscow 85, 213–223 (2020). https://doi.org/10.1134/S000629792002008X

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  • DOI: https://doi.org/10.1134/S000629792002008X

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