Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Implications of Prenatal Exposure to Hyperandrogen for Hippocampal Neurodevelopment and Autism-like Behavior in Offspring

ABSTRACT: Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder that significantly jeopardizes the physical and mental well-being of children. Autism spectrum disorder results from a combination of environmental and genetic factors. Hyperandrogenic exposure during pregnancy increases their risk of developing autism. Nevertheless, the prenatal exposure to androgens affects offspring neurodevelopment and the underlying mechanisms have not been fully elucidated. In the present study, administration of excessive dihydrotestosterone (DHT) to pregnant mice was found to impair neuronal development and dendritic spine formation in offspring, inducing autism-like behaviors. Furthermore, through mRNA transcriptome sequencing technology, the key molecule Nr4a2 was identified during this process of change. Overexpression of Nr4a2 and treatment with amodiaquine (AQ) significantly improved the abnormal phenotypes in offspring caused by prenatal exposure to androgens. Overall, Nr4a2 emerges as a crucial molecule involved in the impairment of offspring neurodevelopment due to prenatal androgen exposure, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms.

ORGANISM(S): Mus musculus

PROVIDER: GSE246534 | GEO | 2023/11/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Persistent transcriptomic alterations in medial prefrontal cortex after prenatal exposure to maternal inflammation

Project description:Infection during pregnancy is strongly implicated as an environmental risk factor for autism spectrum disorder (ASD), with activation of the maternal immune system (MIA) identified in the causative pathway. Maternal exposure to viral and bacterial mimics at midgestation leads to the development of core ASD behaviors in rodent offspring. However, the fundamental pathogenic mechanisms coupling MIA to persistent changes in brain function and behavior are incompletely understood.The medial prefrontal cortex (mPFC) is a major locus of pathology in ASD and highly associated with behaviors dysregulated by MIA. Transcriptomic profiling of the mPFC from adult MIA and control offspring provides insight into molecular pathways persistently disrupted by prenatal exposure to maternal inflammation.

2018-07-26 | GSE117327 | GEO

The effects of fetal prenatal androgen and estrogenic exposure on the health of adult animals

Project description:Prenatal exposure to androgens and estrogens and their effect on liver development

2020-01-09 | PXD014050 | Pride

HDAC3 Inhibition Causes the Impairment in Development of Neocortical VIP Interneurons via dysregulation of Notch Signaling and Autism-like Behaviors

Project description:Autism spectrum disorders (ASDs) are a neurodevelopmental disorder characterized by impairments in social interactions and stereotyped behaviors. While ASD has a strong genetic background, environmental factors including toxins, pesticides, infection and drugs are also known to confer autism susceptibility, likely by inducing epigenetic changes. Exposure to Valproic acid (VPA), a drug for epilepsy and bipolar disorders, during pregnancy is highly associated with the risk of ASD children. In rodents, in utero VPA exposure can precipitate behavioral phenotypes related to ASD in the offspring. Since VPA is an inhibitor of histone deacethytransferase (HDAC) activity, it thought to cause ASD with epigenetic modification. However, the core mechanism by which prenatal VPA exposure causes onset of ASD is still not fully uncovered. Here we revealed that prenatal VPA exposure strongly influences development of vasoactive intestinal peptide (VIP) - positive neurons, a subtype of cortical GABAergic interneurons. The number of VIP+ interneurons was severely reduced in somatosensory area of VPA-exposed ASD animals. We then found that the reduction in VIP+ interneurons is caused by the inhibition of HDAC3 activity upon prenatal VPA exposure. Importantly, prenatal HDAC3 inhibition caused not only the selective reduction in VIP+ interneurons but also the ASD-like behaviors in mice. We then demonstrated that the HDAC3 inhibition aberrantly activates Notch signaling, which influences the cell fate determination of VIP+ interneuron progenitors in caudal ganglionic eminence. Thus, this study uncovers the mechanism by which specific HDAC inhibition during development influences a specific type of GABAergic interneurons in the ASD model. The findings provide a novel insight into the understanding of ASD pathophysiology.

2022-06-20 | GSE133932 | GEO

Effects of prenatal valproic acid exposure on hippocampal gene expression after birth

Project description:Valproic acid (VPA) is a clinically used antiepileptic drug, but it has significant risks for low verbal intelligence quotient scores, attention deficit hyperactivity disorder and autism spectrum disorder in children when it is administered during pregnancy. Prenatal VPA exposure is reported to affect neurogenesis and neuronal migration and differentiation. In addition, growing evidence showed that a brain immune cell, microglia are activated by VPA treatment. However, a role of activated microglia by VPA remains unclear. The purpose of this study is identify a candidate gene which is responsible for VPA-induced behavioral disorders.

2021-07-23 | GSE180564 | GEO

gene expression profile of hippocampus from offspring exposure to maternal excessive estradiol

Project description:Accumulating researches suggest that exposure to abnormal environment in the uterus causes chronic diseases in future life. High intrauterine estradiol level is a major characteristic of in vitro fertilization. Here, we explored the potential neurodevelopment harm and behavior disorder of prenatal high estradiol exposure.

2017-06-27 | GSE100456 | GEO

Project description:In this study, we investigated the effects of prenatal bisphenol-A (BPA) exposure on transcriptome profiles in the frontal cortex of the rat offspring. Transcriptome profiling by RNA-seq analysis of frontal cortex tissues isolated from neonatal pups prenatally exposed to BPA revealed that a list of differentially expressed genes (DEGs) associated with autism spectrum disorder (ASD), including Ntng1, Auts2, and Ankrd11 was dysregulated in a sex-specific pattern. The gene ontology analysis revealed that the BPA-responsive genes in the offspring’s frontal cortex were significantly associated with ASD-related neurological functions. These results indicated that prenatal BPA exposure may increase the risk of ASD by impacting ASD-related genes in the offspring’s frontal cortex. We conducted experiments using the frontal cortex from neonatal pups prenatally exposed to BPA or vehicle control (BPA treament; pooled 3 pups frontal cortex, vehicle control; pooled 3 pups frontal cortex). 10-week-old female rats were daily treated with BPA at the concentration of 5,000 microgram/kilogram of maternal body weight or vehicle control from gestation day 1 (GD1) until parturition. Total RNAs were isolated and cDNAs were synthesized. The transcriptome profiles were performed using a high-throughtput RNA-seq.

2023-04-06 | GSE229073 | GEO

GNPS - SEED Grant B0011 - interlukin 6 study

Project description:Role of chronic prenatal cytokine exposure (interlukin 6) on neural and behavior phenotypes associated with autism spectrum disorders (ASD). Data was collected using a Bruker Maxis and C18RP UHPLC

2020-01-14 | MSV000084805 | GNPS

Transcriptional profile of male and female embryonic day 18 (E18) C57Bl6/J mouse dorsal forebrain after chronic maternal infusion with arginine vasopression (AVP) or saline throughout gestation.

Project description:This experiment assessed transcriptional changes in embryonic dorsal forebrain in male and female offspring to determine the sex-specific mechanism(s) by which chronic gestaitonal exposure to arginine vasopression (AVP), a mouse model of the hypertensive gestational disorder preeclampsia, alters neurodevelopment.

2020-11-03 | GSE160676 | GEO

Macaca fascicularis

Project description:Prenatal VPA exposure dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder

| PRJNA391415 | ENA

Transcriptional organization of autism spectrum disorder

Project description:Transcriptional organization of autism spectrum disorder

| PRJNA436104 | ENA