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REVIEW: Prenatal Stress in Maternal Hyperhomocysteinemia: Impairments in the Fetal Nervous System Development and Placental Function

Alexander V. Arutjunyan1,2,a*, Gleb O. Kerkeshko2, Yuliya P. Milyutina1, Anastasiia D. Shcherbitskaia1,3, and Irina V. Zalozniaia1

1Research Institute of Obstetrics, Gynecology and Reproductology named after D.O.Ott, 199034 St. Petersburg, Russia

2St. Petersburg Institute of Bioregulation and Gerontology, 197110 St. Petersburg, Russia

3Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 104223 St. Petersburg, Russia

* To whom correspondence should be addressed.

Received December 18, 2020; Revised February 19, 2021; Accepted February 19, 2021
The article presents current views on maternal hyperhomocysteinemia (HHcy) as an important factor causing prenatal stress and impaired nervous system development in fetuses and newborns in early ontogenesis, as well as complications in adulthood. Experimental data demonstrate that prenatal HHcy (PHHcy) affects the morphological maturation of the brain and activity of its neurotransmitter systems. Cognitive deficit observed in the offspring subjected to PHHcy in experimental studies can presumably cause the predisposition to various neurodegenerative diseases, as the role of maternal HHcy in the pathogenesis such diseases has been proven in clinical studies. The review also discusses molecular mechanisms of the HHcy neurotoxic action on the nervous system development in the prenatal and early postnatal periods, which include oxidative stress, apoptosis activation, changes in the DNA methylation patterns and microRNA levels, altered expression and processing of neurotrophins, and neuroinflammation induced by an increased production of pro-inflammatory cytokines. Special attention is given to the maternal HHcy impact on the placenta function and its possible contribution to the brain function impairments in the offspring. Published data suggest that some effects of PHHcy on the developing fetal brain can be due to the disturbances in the transport functions of the placenta resulting in an insufficient supply of nutrients necessary for the proper formation and functioning of brain structures.
KEY WORDS: early ontogenesis, fetus, newborn, brain, maternal hyperhomocysteinemia, prenatal hyperhomocysteinemia, placenta, angiogenesis, neurogenesis

DOI: 10.1134/S0006297921060092