Abstract
BackgroundMany studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. However, few studies have investigated hypothalamic-pituitary-adrenal (HPA) axis activity and the serotonergic system as a consequence of pregestational stress. In the present study, we investigated the effect of pre-gestational stress on HPA axis activity in maternal rats and their foetuses and examined whether changes in HPA axis activity of maternal rats produced functional changes in the serotonergic system in the brain of foetuses.ResultsWe used the behavioural tests to assess the model of chronic unpredictable stress (CUS) in maternal rats. We found the activity in the open field and sucrose consumption was lower for rats with CUS than for the controls. Body weight but not brain weight was higher for control foetuses than those from the CUS group. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for mothers with CUS before pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine (5-HT) were higher in the hippocampus and hypothalamus of foetuses in the CUS group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA) levels were lower in the hippocampus in foetuses in the CUS group than in the control group. Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS group and in the control group. The ratio of 5-HIAA to 5-HT was significantly lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A receptor were significantly lower in the foetal hippocampus in the CUS group than in the control group, with no significant difference in the hypothalamus. The levels of serotonin transporter (SERT) were lower in both the foetal hippocampus and foetal hypothalamus in the CUS group than in the control group.ConclusionsOur data demonstrate that pre-gestational stress alters HPA axis activity in maternal rats and their foetuses, which is associated with functional changes in 5-HT activity (5-HT, 5-HIAA and ratio of 5-HIAA to 5-HT), as well as the levels of the 5-HT1A receptor and SERT in the hippocampus and hypothalamus of foetuses.
Highlights
Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring
Data in bracket are 95% confidence intervals for each relevant statistic. *, **:P < 0.05, P < 0.01 compared with control by the same week than in the control group, and 5-hydroxyindoleacetic acid (5-HIAA) levels were lower in the hippocampus in foetuses in the chronic unpredictable stress (CUS) group than in foetuses in the control group
We found no difference between male or female foetuses in the CUS group and control group in level of 5-hydroxytryptamine 1A (5-HT1A) receptor in the hypothalamus, which suggests that the effect of pre-gestational stress on the hypothalamus might have a closer relationship with the 5-HT1B autoreceptor at the nerve ends
Summary
Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. Many studies in humans and animals have found that emotional disturbance and distress before or during pregnancy that results from natural or human-made disasters, chronic interpersonal tension or adverse conditions in the home or workplace are linked to an increased incidence of behavioural disorders in offspring [1,2,3] These disorders include impaired memory and language development, autism, attention deficits, schizophrenia, anxiety disorder and depression. Humans with depression and decreased SERT levels showed changes in 5-HT1A receptor density [19]; changes in 5-HT1A receptor function were noted in SERT-knockout mice [18] These studies have focused on the effects on offspring of stress exposure during pregnancy. A few studies have examined the effect of chronic unpredictable stress (CUS) before pregnancy on neurobiological variables in offspring [3]
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