| Objective: Epidemiological investigation revealed that women are more likely to suffer from depression than men,and the incidence is more than twice that of men.Incidence in women especially spikes during adolescence,which is associated with estrogen fluctuations during adolescence in women.Prenatal stress(PS)can lead to depression-like behavior in offspring,and the specific mechanism is unclear.This study combines the characteristics of PS offspring and depression in adolescent females,and establishes a PS model to explore whether there are depression-like behavioral differences between males and females in adolescent PS offspring,and whether 17β-estradiol(E2)mediates the depression-like behavior of PS adolescent female offspring by regulating the expression of downstream estrogen receptor α(ERα).Methods: The prenatal restraint stress model was used in the research.Pregnant rats were randomly divided into two groups.The stress group underwent restraint stress in the third trimester,3 times a day at random for 45 minutes per time,while the control group didn’t undergo any stress.After weaning on the 21 st day after birth,the offspring were separated into cages and randomly divided into groups.The sucrose preference test,the open field test and the forced swimming test were performed on each group of adolescent offspring to evaluate the depression-like behavior of offspring,and then the concentration of E2 in the serum of adolescent male and female offspring was detected by ELISA.The expression of ERα in hippocampus of each group of adolescent offspring rats was detected by RT-q PCR and Western blotting assay.Results:1.PS reduced sucrose preference and the number of open field crossing the central grid,rearing and grooming times,prolonged the immobile time of forced swimming,and caused depression-like behavior in adolescent female offspring rats,while PS had no obvious effect in adolescent male offspring rats.Molecular experiments also found that PS significantly reduced the concentration of E2 in the serum and the levels of ERα in the hippocampus of adolescent female offspring rats,but not significantly different in PS adolescent male offspring.2.Ovariectomy(OVX)was used to remove the main source of E2 in adolescent female rats.The behavioral results before and after surgery showed that the surgery decreased sucrose preference and open field activity,increased the immobile time of forced swimming,and caused depression-like behavior.In addition,the expression level of ERαin hippocampus decreased significantly after surgery.3.After OVX was performed on PS adolescent female offspring to exclude the influence of E2 on downstream ERα,the selective ERα agonist propyl pyrazole triol(PPT)was intraperitoneally injected.The two results of behavioral tests before surgery and after administration showed that sucrose preference and open field activity increased,the immobile time of forced swimming shortened and depression-like behavior significantly improved in PS adolescent female offspring rats after administration.The results of molecular experiments showed that the level of ERα in the hippocampus of the rats was significantly increased after administration.Conclusions: PS caused depression-like behavior in adolescent female offspring rats,but had no significant effect on adolescent male offspring rats,which may be related to the levels of E2 and downstream ERα in female offspring rats.In order to remove the main source of E2,OVX was administered to normal adolescent female rats.Significant depression-like behavior was observed,and the expression of ERα in the hippocampus was decreased.After administration of PPT to PS adolescent female offspring rats,the expression of ERα was significantly increased,and the depression-like behavior was also improved,which further verified that ERα was involved in PS-induced depression in adolescent female offspring rats,and it provides ideas for the treatment of depression in adolescent females. |
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