| Objective This study aims to understand the effect of elective caesarean section on offspring's emotional development and sex specificity,and to investigate the role of key neurotransmitters related to emotion regulation in the association between elective caesarean section and offspring's emotional development.Methods(1)The animal model of caesarean section was established in ICR mice,and the control group was set up.Offspring of caesarean section group and control group were in-fostered by their non-biological mothers at birth.(2)Body weight and brain weight was measured at 0 days(PND 0),14 days(PND14),28 days(PND 28),42 days(PND 42)and 56 days(PND 56)after birth,respectively.Peripheral blood and left brain tissue were collected at PND 42 and PND56.(3)Depression level was evaluated by sugar water preference experiment and forced swimming experiment,and anxiety level was evaluated by open field experiment and elevated cross maze experiment.Sugar water preference experiment was conducted at PND 42 and PND 58 respectively,and the main indicator was the sugar water preference rate.The forced swimming experiment was carried out at PND 47 and PND63 respectively,and the main indicator was immobility time.Open field experiments were carried out in PND 44 and PND 60 respectively,and the main indicators were total distance,average velocity,rearing and grooming times,fecal particle numbers,center square entries,center square duration.The elevated cross maze experiment was carried out in PND 45 and PND 61 respectively,and the main indicators were open arm duration and fecal particle numbers.(4)HE staining was carried out on the offspring's left brain tissue at PND 42 and PND 56 to observe the morphological changes in the amygdala and prefrontal cortex of the two groups in different sexs.(5)Serum levels of offspring's dopamine(DA),homovanillic acid(HVA),5-hydroxytryptamine(5-HT)and 5-hydroxyindoleacetic acid(5-HIAA)at PND 42 and PND 56 were detected by ELISA.Liquid chromatography tandem mass spectrometry was used to detect the levels of above-mentioned four neurotransmitters in the prefrontal cortexResults(1)There was no significant difference in postnatal body weight and brain weight between caesarean section group and control group.(2)The overall sugar water preference rate at PND 42 and PND 58 in caesarean section group was significantly lower than that in the control group.No significant difference in sugar water preference rate was observed between male and female offspring at the two time points.In the forced swimming experiment,there was no significant difference in the immobility time and fecal particle numbers between the two groups.The immobility time in overall and male offspring in caesarean section group was significantly higher than that in the control group at PND 63.Offspring of caesarean section group had a certain degree of depression in adu Lthood,and the males were more sensitive.In the open-field experiment,there was no significant difference in total distance,average velocity,fecal particle numbers,center square entries and center square duration between the two groups at both PND 44 and PND 60.Rearing and grooming times were significantly higher in overall and female caesarean section offspring than those in control group at PND 44.At PND 60,grooming times were significantly higher in the overall and female caesarean section group offspring than those in in the control group,and no significant difference was observed in rearing between the two groups.In the elevated cross maze experiment,there was no significant difference between the two groups in the total open arm duration at PND 45 or PND 61,and no significant sex difference was observed as well.The fecal particle numbers in the overall caesarean section group was significantly higher than that in the control group at PND 61.caesarean section offspring had anxiety symptoms both in adolescence and adulthood,especially in females.(3)HE staining in the amygdala and prefrontal cortex of the two groups at PND 42 and PND 56 showed that the amygdala and prefrontal cortex cells of the control group were more intact and had clearer nucleoli than those of the caesarean section group.In the caesarean section group,there was mild cellular edema in the prefrontal cortex.Some amygdala and prefrontal cortex nuclei became pyknotic and dark,with apoptosis and necrosis.No significant sex difference was observed.(4)At PND 42,the levels of DA,HVA and DA/HVA in prefrontal cortex in overall and female offspring in caesarean section group were significantly higher than those in the control group.At PND 56,the expression levels of DA and HVA in prefrontal cortex in overall offspring in caesarean section group were significantly higher than those in the control group.Higher DA level was observed in male offspring and higher HVA level was found in female offspring in caesarean section group.At PND 42,the levels of 5-HT in prefrontal cortex in female offspring in caesarean section group were significantly lower than those in the control group.Lower5-HIAA level was observed in overall and female offspring in caesarean section group and higher 5-HIAA/5-HT level was found in female offspring in caesarean section group.At PND 56,the 5-HT levels in prefrontal cortex in overall and female offspring in caesarean section group were significantly lower than those in the control group.Lower 5-HIAA level was observed in female offspring and higher 5-HIAA/5-HT level was found in overall,male and female offspring in caesarean section group.At PND 42,the levels of HVA in serum in overall,male and female offspring in caesarean section group were significantly higher than those in the control group.At PND 56,the DA and HVA levels in serum in overall,male and female offspring in caesarean section group were significantly higher than those in the control group.At PND 42,the levels of 5-HT in serum in overall and female offspring in caesarean section group were significantly higher than those in the control group.Higher 5-HIAA level was observed in overall,male and female offspring in caesarean section group.At PND 56,higher 5-HIAA level was found in overall,male and female offspring in caesarean section group.Conclusion The offspring of elective caesarean section had anxiety and depression-like behaviors in adolescence and adu Lthood.Male offspring were sensitive to be depressive and female offspring tended to be anxious.Morphological changes in the prefrontal cortex were observed.Variations in the key neurotransmitters may partly explain the association between elective caesarean section and offspring's emotional symptoms. |
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