I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 St. Petersburg, Russia.
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductive Medicine, 199034 St. Petersburg, Russia.
Cells. 2023 Jan 3;12(1):189. doi: 10.3390/cells12010189.
Maternal hyperhomocysteinemia causes the disruption of placental blood flow and can lead to serious disturbances in the formation of the offspring's brain. In the present study, the effects of prenatal hyperhomocysteinemia (PHHC) on the neuronal migration, neural tissue maturation, and the expression of signaling molecules in the rat fetal brain were described. Maternal hyperhomocysteinemia was induced in female rats by per os administration of 0.15% aqueous methionine solution in the period of days 4-21 of pregnancy. Behavioral tests revealed a delay in PHHC male pups maturing. Ultrastructure of both cortical and hippocampus tissue demonstrated the features of the developmental delay. PHHC was shown to disturb both generation and radial migration of neuroblasts into the cortical plate. Elevated expression, together with changes in proBDNF/mBDNF balance, might affect neuronal cell viability, positioning, and maturation in PHHC pups. Reduced gene expression and the content of SEMA3E might lead to impaired brain development. In the brain tissue of E20 PHHC fetuses, the content of the procaspase-8 was decreased, and the activity level of the caspase-3 was increased; this may indicate the development of apoptosis. PHHC disturbs the mechanisms of early brain development leading to a delay in brain tissue maturation and formation of the motor reaction of pups.
母体高同型半胱氨酸血症会导致胎盘血流紊乱，并可能导致后代大脑形成严重紊乱。本研究描述了产前高同型半胱氨酸血症（PHHC）对大鼠胎脑神经元迁移、神经组织成熟和信号分子表达的影响。通过在妊娠第 4-21 天期间经口给予 0.15% 水甲硫氨酸溶液，诱导雌性大鼠母体高同型半胱氨酸血症。行为测试显示 PHHC 雄性幼鼠成熟延迟。皮质和海马组织的超微结构显示出发育迟缓的特征。PHHC 被证明干扰了神经母细胞向皮质板的生成和放射状迁移。升高的表达，加上 proBDNF/mBDNF 平衡的改变，可能会影响 PHHC 幼鼠神经元的存活、定位和成熟。下调的基因表达和 SEMA3E 的含量可能导致脑发育受损。在 E20 PHHC 胎儿的脑组织中，procaspase-8 的含量减少，caspase-3 的活性水平增加；这可能表明细胞凋亡的发生。PHHC 扰乱了早期大脑发育的机制，导致脑组织成熟延迟和幼鼠运动反应形成延迟。
