Effects Of Maternal Undernutrition During Late Pregnancy On Brain Development And Neurotransmitter Synthesis In Mongolian Ovine Fetuses

The aim of this experiment is to explore the effects of maternal undernutrition during late pregnancy on brain development and neurotransmitter synthesis of fetuses in sheep model.23 healthy and growing Mongolian sheep were selected for the experiment,and they were subjected to estrus synchronization,mating,and other treatments.At 90 days of pregnancy,6 ewes with similar body conditions were selected for slaughter.Then the remaining 17animals were randomly divided into 3 groups,namely CG group(n=5,0.63 MJ ME/BW^0.75/d,free feeding group),MU1 group(n=6,0.33 MJ ME/BW^0.75/d),and MU2 group(n=6,0.20MJ ME/BW^0.75/d).Feed it at this nutritional level until 130 days of pregnancy for slaughter.Fetal brain tissue was taken and weighed before subsequent experiments were conducted.The results are as follows:（1）Under the conditions of this experiment,at 130 days of pregnancy,the fetal weight and head weight of the MU2 group were significantly lower than those of the MU1 group（P<0.01）and CG group（P<0.01）;There was no significant difference in total fetal brain weight（P>0.05）and brain weight（P>0.05）among the three groups;The fetal cerebellum and brainstem in the MU2 group were significantly reduced compared to the CG group（P<0.05）;The fetal brain weight/body weight（P<0.01）and brain weight/liver weight（P<0.01）showed a significant upward trend with decreasing nutritional levels.（2）Under the conditions of this experiment,as the maternal nutritional level decreases,at 130 days of pregnancy,the gaps in various brain tissues increase and the level of brain connectivity decreases.The thickness of the fetal cerebellar molecular layer（P<0.05）significantly thinned,while the gray matter layer（P>0.05）showed a trend of thinning.The density of white matter cells in the brain（P>0.05）and cerebellum（P>0.05）showed a decreasing trend.The DNA content of the cerebellum showed a decreasing trend（P>0.05）;The protein（P<0.01）and DNA（P<0.05）contents of the brainstem were significantly reduced.（3）Under the conditions of this experiment,with the decrease of maternal nutrition level,at 130 days of pregnancy,the concentrations of 5-HT（P<0.05）,DA（P<0.05）,and ACH（P<0.05）in the fetal brain,as well as DA and GABA in the cerebellum,were significantly reduced（P<0.05）;There were no significant changes in 5-HT,DA,ACH,and GABA in the brainstem among the three groups（P>0.05）,with a decreasing trend in 5-HT.（4）Under the conditions of this experiment,at 130 days of pregnancy,the expression level of TPH2（P<0.01）gene in the brain of fetuses in the low nutrition group was significantly reduced compared to the CG group.The expression of CHAT（P<0.05）in the MU2 group was significantly lower than that in the CG group,and the expression of DDC gene（P>0.05）showed a decreasing trend.The expression levels of DDC（P<0.01）,GAD1（P<0.01）,and GAD2（P<0.05）genes in the cerebellum were significantly reduced.The expression levels of TPH2（P<0.05）,DDC（P<0.01）,CHAT（P<0.01）,GAD1（P<0.01）,and GAD2（P<0.01）genes in the brainstem were significantly reduced.In summary,maternal malnutrition leads to a decrease in the weight of the cerebellum and brainstem of IUGR fetuses,as well as a decrease in DNA content.The thickness of the gray matter layer and the density of white matter layer cells in the cerebellum show a decrease,while the levels of neurotransmitters and the expression of neurotransmitter synthase related genes in the cerebrum,cerebellum,and brainstem decrease to varying degrees.Therefore,maternal malnutrition in the later stages of pregnancy affects the growth and development of various brain tissues and the synthesis of neurotransmitters in IUGR fetuses to varying degrees.