Abstract

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.

中文翻译：

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母体高同型半胱氨酸血症的产前压力：胎儿神经系统发育和胎盘功能受损

摘要

本文介绍了当前对母体高同型半胱氨酸血症 (HHcy) 的看法，它是导致胎儿和新生儿早期出生压力和神经系统发育受损以及成年期并发症的重要因素。实验数据表明，产前 HHcy (PHHcy) 会影响大脑的形态成熟及其神经递质系统的活动。在实验研究中观察到接受 PHHcy 的后代的认知缺陷可能会导致易患各种神经退行性疾病，因为母体 HHcy 在此类疾病的发病机制中的作用已在临床研究中得到证实。该综述还讨论了 HHcy 神经毒性作用对产前和产后早期神经系统发育的分子机制，包括氧化应激、细胞凋亡激活、DNA 甲基化模式和 microRNA 水平的变化、神经营养因子的表达和加工改变，以及促炎细胞因子产生增加引起的神经炎症。特别注意母体 HHcy 对胎盘功能的影响及其对后代脑功能损伤的可能影响。已发表的数据表明，PHHcy 对发育中的胎儿大脑的一些影响可能是由于胎盘转运功能的紊乱导致大脑结构正常形成和运作所需的营养供应不足。以及由促炎细胞因子产生增加引起的神经炎症。特别注意母体 HHcy 对胎盘功能的影响及其对后代脑功能损伤的可能贡献。已发表的数据表明，PHHcy 对发育中的胎儿大脑的一些影响可能是由于胎盘转运功能的紊乱导致大脑结构正常形成和运作所需的营养供应不足。以及由促炎细胞因子产生增加引起的神经炎症。特别注意母体 HHcy 对胎盘功能的影响及其对后代脑功能损伤的可能影响。已发表的数据表明，PHHcy 对发育中的胎儿大脑的一些影响可能是由于胎盘转运功能的紊乱导致大脑结构正常形成和运作所需的营养供应不足。