Prenatal fear stress impairs cognitive development in offspring rats by disrupting placental amino acid transport.
10.12122/j.issn.1673-4254.2025.08.02
- Author:
Zhixin DU
1
;
Yueyang WANG
1
;
Liping YANG
1
;
Junlin HOU
1
;
Jianhua SUN
2
;
Pengbei FAN
3
;
Yaohui WANG
1
;
Xiaolin LI
1
Author Information
1. School of Traditional Chinese Medicine, Henan University of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
2. Department of Obstetrics and Gynecology, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China, Southern Medical University, Guangzhou 510515, China.
3. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
- Publication Type:Journal Article
- Keywords:
amino acid transport;
cognition development;
fear stress;
offspring emotion;
placenta
- MeSH:
Animals;
Female;
Pregnancy;
Placenta/metabolism*;
Fear;
Rats;
Rats, Wistar;
Cognition;
Prenatal Exposure Delayed Effects;
Stress, Psychological;
Amino Acids/blood*;
Amino Acid Transport Systems/metabolism*
- From:
Journal of Southern Medical University
2025;45(8):1581-1588
- CountryChina
- Language:Chinese
-
Abstract:
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.
