Hematopoietic stem cell transplantation ameliorates maternal diabetes–mediated gastrointestinal symptoms and autism‐like behavior in mouse offspring

Zeng, Jiaying; Liang, Yujie; Sun, Ruimin; Huang, Saijun; Wang, Zi-Chen; Xiao, Li; Jiang, Lu; Yu, Hong; Yao, Paul

doi:10.1111/nyas.14766

Cited by 11 publications

(22 citation statements)

References 46 publications

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“…Furthermore, our previous study showed that prenatal factor exposure mediates gene suppression in hypothalamus, hippocampus and amygdala, especially the amygdala plays a dominant role in ALB (Zou et al, 2017); therefore, we focus on the potential effect in amygdala and related gene expression in this work. In addition, we have previously found that prenatal factor exposure‐mediated oxidative stress (Liu et al, 2022) and epigenetic changes can also happen in hematopoietic stem cells (HSCs), and this can be inherited by PBMCs during subsequent embryonic differentiation (Lu et al, 2020; Zeng et al, 2022). In this case, the gene expression from both HSC and PBMC was determined from prenatal factor exposure‐mediated offspring.…”

Section: Introductionmentioning

confidence: 99%

“…In this case, the gene expression from both HSC and PBMC was determined from prenatal factor exposure‐mediated offspring. In order to evaluated the ALBs in mouse offspring, the ultrasonic vocalization (USV), social interaction (SI) test and three‐chambered social test were employed based on our previous report (Wang et al, 2019; Zeng et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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Prenatal exposure of diabetes and progestin‐mediated autistic biomarker in peripheral blood mononuclear cells

Jiao¹,

Wang²,

Li³

et al. 2023

Eur J of Neuroscience

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Despite the importance of early diagnosis and intervention, the diagnosis of autism spectrum disorders (ASDs) remains delayed as it is mostly based on clinical symptoms and abnormal behaviours appearing after 2 years of age. Identification of autistic markers remains a top priority in achieving an early and effective ASD diagnosis. We have previously reported that prenatal exposure of hormones or diabetes triggers epigenetic changes and oxidative stress, resulting in gene suppression with autism-like behaviours in offspring. Here, a potential biomarker for ASD diagnosis was established through gene analysis in peripheral blood mononuclear cells (PBMCs). The study from in vivo mouse showed that prenatal hormone exposure or maternal diabetes suppresses mRNA expression of estrogen-related receptor α (ERRα), superoxide dismutase 2 (SOD2), G protein-coupled estrogen receptor (GPER) and retinoic acid-related orphan receptor α (RORA) in the brain as well as oxidative stress and mitochondrial dysfunction, subsequently triggering autism-like behaviour in mouse offspring. Also, similar gene suppression was found in hematopoietic stem cells (HSCs) and PBMC, with inherited epigenetic changes being identified on the related promoters. The human case-control study found that mRNA levels of ERRα, SOD2, GPER and RORA were significantly reduced in PBMC from ASD subjects (n = 132) compared with typically developing (n = 135) group. The receiver operating characteristic curve showed a .869 ± .021 of area under the curve for ASD subjects with 95% confidence interval of .829-.909, together with 1.000 of sensitivity and .856 of specificity. In conclusion, the combined mRNA expression in PBMC based on prenatal factor exposure-mediated gene suppression could be a potential biomarker for ASD diagnosis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prenatal exposure of diabetes and progestin‐mediated autistic biomarker in peripheral blood mononuclear cells

Jiao¹,

Wang²,

Li³

et al. 2023

Eur J of Neuroscience

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“…We have previously reported that transplantation of HSC with SOD2 expression can partly reverse maternal diabetes‐induced ALB and GI dysfunction, indicating that HSCT with related gene manipulation may be a potential choice for treatment [24]. In this study, we found that HSCT with CLDN1 expression can partly reverse prenatal 17‐OHPC exposure‐mediated GI dysfunction, but has no effect on ALB, indicating that CLDN1 suppression in IEC may partly contribute to prenatal 17‐OHPC exposure‐mediated GI dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Autism‐like behavior of murine offspring induced by prenatal exposure to progestin is associated with gastrointestinal dysfunction due to claudin‐1 suppression

Xiao

Feng²,

Zhang

et al. 2023

The FEBS Journal

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Autism spectrum disorders (ASD) are associated with the contribution of many prenatal risk factors; in particular, the sex hormone progestin and vitamin D receptor (VDR) are associated with gastrointestinal (GI) symptoms in ASD development, although the related mechanism remains unclear. We investigated the possible role and mechanism of progestin 17‐hydroxyprogesterone caproate (17‐OHPC) exposure‐induced GI dysfunction and autism‐like behaviours (ALB) in mouse offspring. An intestine‐specific VDR‐deficient mouse model was established for prenatal treatment, while transplantation of haematopoietic stem cells (HSCT) with related gene manipulation was used for postnatal treatment for 17‐OHPC exposure‐induced GI dysfunction and ALB in mouse offspring. The in vivo mouse experiments found that VDR deficiency mimics prenatal 17‐OHPC exposure‐mediated GI dysfunction, but has no effect on 17‐OHPC‐mediated autism‐like behaviours (ALB) in mouse offspring. Furthermore, prenatal 17‐OHPC exposure induces CLDN1 suppression in intestine epithelial cells, and transplantation of HSCT with CLDN1 expression ameliorates prenatal 17‐OHPC exposure‐mediated GI dysfunction, but has no effect on 17‐OHPC‐mediated ALB in offspring. In conclusion, prenatal 17‐OHPC exposure triggers GI dysfunction in autism‐like mouse offspring via CLDN1 suppression, providing a possible explanation for the involvement of CLDN1 and VDR in prenatal 17‐OHPC exposure‐mediated GI dysfunction with ASD.

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“…A growing number of studies have explored the relationship between metabolic disorders and psychiatric disorders, and there has been a gradual increase in research on the relationship between diabetes and psychiatric disorders, as well as a large body of literature exploring the effect of maternal diabetes on the development of neurodevelopmental disorders in offspring (61)(62)(63)(64)(65), but the detailed mechanisms remain unclear. Meanwhile, there are fewer original studies on the comorbid psychiatric disorders in patients with T1DM.…”

Section: Discussionmentioning

confidence: 99%

Association between type 1 diabetes and neurodevelopmental disorders in children and adolescents: A systematic review and meta-analysis

et al. 2022

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Type 1 diabetes and neurodevelopmental disorders are common chronic conditions in childhood and adolescence, and having one may lead to an increased chance of developing the other. Type 1 diabetes mellitus is mainly manifested by elevated blood glucose, while neurodevelopmental diseases are composed of a variety of diseases, which are relatively complex. The purpose of this meta-analysis was to find out the prevalence of type 1 diabetes-related neurodevelopmental disorders in children and adolescents and to explore the potential association between neurodevelopmental disorders and type 1 diabetes. PubMed, Embase and Web of science databases were searched from the inception to May 22, 2022 to identify relevant studies, Finally, 24 original studies were included in the meta-analysis. Prevalence estimates for neurodevelopmental disorders in the type 1 diabetes adolescent and their 95% confidence intervals were pooled using random effects models. The pooled estimates for autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) in the type 1 diabetes population were 1.2 and 5.3%, respectively, both of which are higher than the 2019 global prevalence of ASD and ADHD in the general population. The results of the subgroup analysis showed that the prevalence of ASD and ADHD in the T1DM population tended to increase with age. In conclusion, there may be a potential link between the occurrence of type 1 diabetes mellitus and the development of neurodevelopmental disorders in children and adolescents, but more relevant studies are needed to understand the link between the underlying pathogenesis of type 1 diabetes and neurodevelopmental disorders.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/], identifier [CDR42022333443].

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Hematopoietic stem cell transplantation ameliorates maternal diabetes–mediated gastrointestinal symptoms and autism‐like behavior in mouse offspring

Cited by 11 publications

References 46 publications

Prenatal exposure of diabetes and progestin‐mediated autistic biomarker in peripheral blood mononuclear cells

Prenatal exposure of diabetes and progestin‐mediated autistic biomarker in peripheral blood mononuclear cells

Autism‐like behavior of murine offspring induced by prenatal exposure to progestin is associated with gastrointestinal dysfunction due to claudin‐1 suppression

Association between type 1 diabetes and neurodevelopmental disorders in children and adolescents: A systematic review and meta-analysis

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