Hematopoietic stem cell transplantation ameliorates maternal diabetes-mediated gastrointestinal symptoms and autism-like behavior in mouse offspring. 2022

Jiaying Zeng, and Yujie Liang, and Ruoyu Sun, and Saijun Huang, and Zichen Wang, and Li Xiao, and Jianpin Lu, and Hong Yu, and Paul Yao
Department of Child HealthCare, Affiliated Foshan Maternity & Child Healthcare Hospital, The Second School of Clinical Medicine of Southern Medical University, Foshan, P. R. China.

Epidemiological studies have shown that maternal diabetes is associated with autism spectrum disorder development, although the detailed mechanism remains unclear. We have previously found that maternal diabetes induces persistent epigenetic changes and gene suppression in neurons, subsequently triggering autism-like behavior (ALB). In this study, we investigated the potential role and effect of hematopoietic stem cells (HSCs) on maternal diabetes-mediated gastrointestinal (GI) dysfunction and ALB in a mouse model. We show in vitro that transient hyperglycemia induced persistent epigenetic changes and gene suppression of tight junction proteins. In vivo, maternal diabetes-mediated oxidative stress induced gene suppression and inflammation in both peripheral blood mononuclear cells and intestine epithelial cells, subsequently triggering GI dysfunction with increased intestinal permeability and altered microbiota compositions, as well as suppressed gene expression in neurons and subsequent ALB in offspring; HSC transplantation (HSCT) ameliorates this effect by systematically reversing maternal diabetes-mediated oxidative stress. We conclude that HSCT can ameliorate maternal diabetes-mediated GI symptoms and autism-like behavior in mouse offspring.

UI MeSH Term Description Entries
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D005260 Female Females
D005767 Gastrointestinal Diseases Diseases in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM. Cholera Infantum,Gastrointestinal Disorders,Functional Gastrointestinal Disorders,Gastrointestinal Disorders, Functional,Disease, Gastrointestinal,Diseases, Gastrointestinal,Functional Gastrointestinal Disorder,Gastrointestinal Disease,Gastrointestinal Disorder,Gastrointestinal Disorder, Functional
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000067877 Autism Spectrum Disorder Wide continuum of associated cognitive and neurobehavioral disorders, including, but not limited to, three core-defining features: impairments in socialization, impairments in verbal and nonverbal communication, and restricted and repetitive patterns of behaviors. (from DSM-V) Autistic Spectrum Disorder,Autism Spectrum Disorders,Autistic Spectrum Disorders,Disorder, Autistic Spectrum
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001321 Autistic Disorder A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-V) Autism, Infantile,Kanner's Syndrome,Autism,Autism, Early Infantile,Disorder, Autistic,Disorders, Autistic,Early Infantile Autism,Infantile Autism,Infantile Autism, Early,Kanner Syndrome,Kanners Syndrome
D016640 Diabetes, Gestational Diabetes mellitus induced by PREGNANCY but resolved at the end of pregnancy. It does not include previously diagnosed diabetics who become pregnant (PREGNANCY IN DIABETICS). Gestational diabetes usually develops in late pregnancy when insulin antagonistic hormones peaks leading to INSULIN RESISTANCE; GLUCOSE INTOLERANCE; and HYPERGLYCEMIA. Diabetes Mellitus, Gestational,Diabetes, Pregnancy-Induced,Gestational Diabetes,Diabetes, Pregnancy Induced,Gestational Diabetes Mellitus,Pregnancy-Induced Diabetes
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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