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Biochemistry (Moscow). Papers in Press. Published on December 16, 2019 as Manuscript BM19-137.

Neurotrophins of the Fetal Brain and Placenta in Prenatal Hyperhomocysteinemia

A. V. Arutjunyan1,a*, Yu. P. Milyutina1, A. D. Shcherbitskaia2, G. O. Kerkeshko1, I. V. Zalozniaia1, and A. V. Mikhel1

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

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

*To whom correspondence should be addressed.

Received September 25, 2019; Revised October 28, 2019; Accepted November 11, 2019
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 interleukin-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.
KEY WORDS: prenatal hyperhomocysteinemia, neurotrophic factors, proinflammatory cytokines, placenta, fetus brain