Maternal Obesity Results In Autism-like Behaviors In Offspring Mice And Its Epigenetic Mechanism

Object: From the perspective of human epidemiology and animal experiments,it is proved that maternal nutritional condition is closely related to the offspring development.An example of it is that the incidence of maternal obesity is significantly related to the risk of neurodevelopmental disorders in offspring.Autism spectrum disorder is one of the most common neurodevelopmental disorders whose pathogenesis has not been perfected.Micro RNA(miRNA),as one of the ways of epigenetic modification,makes a vital role in ASD.TARDBP(TAR DNA-binding protein-43,TDP-43)is a DNA/RNA binding protein that can regulate the biosynthesis of miRNA and make its expression change.This article aims to study the correlation between maternal obesity and offspring autism,the epigenetic mechanism,and the role of TDP-43 in this phenomenon.Methods: First,we collected six umbilical cord blood samples from overweight or normal pregnant women’s newborns respectively for second-generation high-throughput sequencing,and some of differentially expressed miRNAs were selected as candidate factors.In the laboratory,female C57 BL / 6J mice were continuously given a high fat diet(HFD)or a regular diet(RD)for 12 weeks.Females that reached the standard weight were paired with C57BL/6J adult male mice produce subject offspring.The offspring mice were subjected to a series of behavioral tests including three-chamber social preference test,elevated plus-maze test,repeated actions test,et al.The prefrontal cortex tissues of mice at different ages and after behavioral testing were used to detect the expression of three candidate miRNAs in mouse brain by RT-qPCR.These tissues were also used to detect TDP-43 at m RNA,protein and morphological levels by RT-qPCR,western blot and immunofluorescence respectively.Results:(1)There were 21 miRNAs in the cord blood of the obese group had significant changes.(2)The mice in the HFD group got more weight significantly than the RD group.(3)The offspring mice in the HFD group performed autism-like behaviors in behavioral tests,such as low sociability,increased repetitive/stereotypic behaviors and obvious anxiety.In addition,the HFD offspring suffered from a degree of motor deficit.(4)Consistent with(1),miR-100-5p reduced 25% in HFD offspring compared with RD offspring.(5)The expression of TDP-43 was time-dependent and it in HFD offspring significantly increased to 1.8 times of RD offspring.Conclusions: There were differences in miRNA expression profiles in umbilical cord blood of newborns from obese mothers.Offspring mice from obesity maternal showed obvious autism-like behaviors,and the expression of corresponding miRNA had significantly changed.This phenomenon was accompanied by the upregulation of TDP-43 protein expression,which might be related to the regulation of miRNA expression.