de la Monte Suzanne M, Tong Ming, Ziplow Jason, Mark Princess, Van Stephanie, Nguyen Van Ahn
Departments of Pathology and Laboratory Medicine, Neurosurgery, and Neurology, Rhode Island Hospital, Providence, RI, USA.
Women & Infants Hospital, Brown University Health, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
J Behav Brain Sci. 2025 Feb;15(2):11-46. doi: 10.4236/jbbs.2025.152002. Epub 2025 Feb 26.
Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Gestational dietary soy prevents alcohol-related impairments in placentation and FASD-associated fetal anomalies.
This study was designed to determine if gestational dietary soy would be sufficient to normalize cognitive function in young adolescent offspring after chronic in utero exposure to alcohol. In addition, efforts were made to characterize the mechanisms of FASD prevention by maternal dietary soy.
Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source from gestation day 6 through delivery/postnatal day 0 (P0). From P24 - P28, the offspring were subjected to Morris water maze (MWM) testing, and on P35, they were sacrificed to harvest temporal lobes for histopathologic and molecular studies.
The in-utero ethanol-exposed offspring exhibited significant performance impairments on the MWM test, and they had a significantly reduced mean brain weight with neuronal loss in the CA1 hippocampal region and evidence of white matter myelin loss. Gestational dietary soy nearly normalized MWM performance and preserved brain weight, hippocampal CA1 architecture, and white matter myelin staining in alcohol-exposed offspring. Mechanistically, the main positive effects of soy included increased temporal lobe expression of HES-1 and HIF-1, reflecting enhanced Notch signaling, and broadly increased expression of GnRH network molecules, including Erb1, Gper1, GnRH, GnRH-R, KiSS, and KiSS-R, irrespective of gestational ethanol exposure.
Dietary soy intervention early in pregnancy may reduce FASD-associated cognitive deficits. The findings suggest that targeting Notch and GnRH-related networks may help reduce long-term disability with FASD. Additional mechanistic and experimental research is needed to determine if longer-duration, postnatal dietary soy could prevent the adverse neurobehavioral effects of FASD.
实验性胎儿酒精谱系障碍（FASD）中的神经发育异常与通过介导神经元存活、生长、迁移、能量代谢和可塑性的复杂途径的信号传导受损有关。孕期饮食中的大豆可预防与酒精相关的胎盘形成受损以及FASD相关的胎儿异常。
本研究旨在确定孕期饮食中的大豆是否足以使慢性子宫内酒精暴露的年轻青春期后代的认知功能正常化。此外，还努力阐明母体饮食中的大豆预防FASD的机制。
从妊娠第6天至分娩/出生后第0天（P0），给怀孕的Long Evans大鼠喂食等热量的液体饮食，其中含有0%或26%热量的乙醇，以酪蛋白或大豆分离物作为蛋白质来源。从P24 - P28，对后代进行莫里斯水迷宫（MWM）测试，并在P35时将其处死，以获取颞叶用于组织病理学和分子研究。
子宫内乙醇暴露的后代在MWM测试中表现出明显的行为障碍，并且平均脑重显著降低，海马CA1区有神经元丢失，并有白质髓鞘丢失的迹象。孕期饮食中的大豆几乎使酒精暴露后代的MWM表现正常化，并保留了脑重、海马CA1结构和白质髓鞘染色。从机制上讲，大豆的主要积极作用包括增加颞叶中HES-1和HIF-1的表达，反映Notch信号增强，以及GnRH网络分子（包括Erb1、Gper1、GnRH、GnRH-R、KiSS和KiSS-R）的广泛表达增加，无论孕期是否暴露于乙醇。
孕期早期的饮食大豆干预可能会减少与FASD相关的认知缺陷。研究结果表明，针对Notch和GnRH相关网络可能有助于减少FASD导致的长期残疾。需要进行更多的机制和实验研究，以确定更长时间的产后饮食大豆是否可以预防FASD的不良神经行为影响。
