Ott Institute of Obstetrics, Gynecology, and Reproductology, St. Petersburg, 199034, Russia.
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, 194223, Russia.
Biochemistry (Mosc). 2020 Feb;85(2):213-223. doi: 10.1134/S000629792002008X.
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.
孕期高同型半胱氨酸血症（PHHC）通过慢性 L-蛋氨酸负荷诱导大鼠发生，导致母亲血液和胎儿血液及大脑中的 L-同型半胱氨酸含量显著增加。在妊娠第 20 天的形态计量学研究中，发现胎盘、胎儿和胎儿大脑的重量显著减轻。PHHC 还通过增加大鼠血液和胎盘胎儿部分中促炎白细胞介素-1β的含量而激活母体免疫系统。PHHC 使胎盘和胎儿大脑中脑源性神经营养因子（BDNF，29 kDa）和神经生长因子（NGF，31 kDa）前体的水平升高，胎儿大脑中 BDNF 同工型（29 kDa）的含量升高。在胚胎发育第 20 天，胎盘中的神经调节蛋白 1（NRG1）含量减少，而胎儿大脑中的含量增加。在 PHHC 处理的胎儿大脑中检测到 caspase-3 活性增加。这表明，由 PPHC 诱导的神经营养因子加工变化、由其引发的氧化应激和炎症过程以及细胞凋亡，在后代的大脑发育障碍中起重要作用。
