产前恐惧应激通过破坏胎盘氨基酸转运损害子代大鼠的认知发育
[Prenatal fear stress impairs cognitive development in offspring rats by disrupting placental amino acid transport].
作者信息
DU Zhixin, Wang Yueyang, Yang Liping, Hou Junlin, Sun Jianhua, Fan Pengbei, Wang Yaohui, Li Xiaolin
机构信息
School of Traditional Chinese Medicine, Henan University of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Department of Obstetrics and Gynecology, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China, Southern Medical University, Guangzhou 510515, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2025 Aug 20;45(8):1581-1588. doi: 10.12122/j.issn.1673-4254.2025.08.02.
OBJECTIVES
To investigate the impact of prenatal fear stress on placental amino acid transport and emotion and cognition development in offspring rats.
METHODS
Thirty pregnant Wistar rats were randomized equally into control and fear stress (induced using an observational foot shock model) groups. In each group, placental and serum samples were collected from 6 dams on gestational day 20, and the remaining rats delivered naturally and the offspring rats were raised under the same conditions until 8 weeks of age. Emotional and cognitive outcomes of the offspring rats were assessed with behavioral tests, and placental structure was examined using HE staining. Bioinformatics analysis was used to identify differentially expressed placental transporter genes under fear stress. The expressions of system A and system L amino acid transporters, along with other specialized transporters, were detected using qRT-PCR and Western blotting. Fetal serum amino acid concentrations were determined by HPLC. The correlations between fetal amino acid levels and behavioral outcomes of the offspring rats were analyzed.
RESULTS
The dams with fear stress showed reduced open-field activity and increased freezing behavior with significantly decreased placental weight, fetal weight, and fetal-to-placental ratio. Bioinformatics analysis revealed 28 differentially expressed transporter genes involved mainly in amino acid transport. In the fear stress group, fetal serum amino acid levels were significantly lowered and Slc38a1, Slc43a1, Slc43a2, Slc7a8, Slc6a6, Slc1a1 and Slc6a9 mRNA and protein expressions were all downregulated. The offspring rats in fear stress group exhibited decreased novel object preference and spontaneous alternation with reduced open arm exploration and increased immobility in emotional tests. Lower early-life amino acid levels was found to correlate with impaired adult cognition.
CONCLUSIONS
Prenatal fear stress in rats impairs placental amino acid transporter expression and reduces fetal serum amino acid levels, potentially contributing to long-term cognitive deficits in the offspring rats.
目的
探讨产前恐惧应激对胎盘氨基酸转运以及子代大鼠情绪和认知发育的影响。
方法
将30只妊娠Wistar大鼠随机均分为对照组和恐惧应激组（采用观察性足部电击模型诱导）。每组于妊娠第20天从6只母鼠采集胎盘和血清样本，其余大鼠自然分娩，子代大鼠在相同条件下饲养至8周龄。采用行为测试评估子代大鼠的情绪和认知结果，用苏木精-伊红染色检查胎盘结构。利用生物信息学分析确定恐惧应激下胎盘转运蛋白基因的差异表达。采用实时定量聚合酶链反应和蛋白质免疫印迹法检测A系统和L系统氨基酸转运蛋白以及其他特异性转运蛋白的表达。用高效液相色谱法测定胎儿血清氨基酸浓度。分析胎儿氨基酸水平与子代大鼠行为结果之间的相关性。
结果
遭受恐惧应激的母鼠旷场活动减少、僵住行为增加，胎盘重量、胎儿体重和胎儿与胎盘重量比显著降低。生物信息学分析显示28个差异表达的转运蛋白基因，主要参与氨基酸转运。在恐惧应激组中，胎儿血清氨基酸水平显著降低，溶质载体家族38成员1（Slc38a1）、溶质载体家族43成员1（Slc43a1）、溶质载体家族43成员2（Slc43a2）、溶质载体家族7成员8（Slc7a8）、溶质载体家族6成员6（Slc6a6）、溶质载体家族1成员1（Slc1a1）和溶质载体家族6成员9（Slc6a9）的信使核糖核酸和蛋白质表达均下调。恐惧应激组的子代大鼠在新物体偏好和自发交替试验中表现下降，在情绪测试中开放臂探索减少、不动时间增加。发现生命早期氨基酸水平较低与成年后认知受损相关。
结论
大鼠产前恐惧应激会损害胎盘氨基酸转运蛋白表达，降低胎儿血清氨基酸水平，可能导致子代大鼠长期认知缺陷。
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