ArticleMolecular autism2017
Prenatal levonorgestrel exposure induces autism-like behavior in offspring through ERβ suppression in the amygdala.
Article in Molecular autism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Steroidopathies and hormonal imbalance in children and adolescents with autism spectrum disorder.JCPP advances · 2026Article
- Prenatal bisphenol A exposure reprograms SF1-lactylation pathways to promote endometriosis susceptibility.iScience · 2026Article
- Early-life oxidative stress programs persistent NFκB activation and neuroinflammation in autism spectrum disorder.Frontiers in immunology · 2026Article
- Valproate-Induced Autism and Sexual Hormone Disturbances: A Literature Review and Hypotheses.Neurochemical research · 2025Review
- Effects of Endocrine-Disrupting Chemicals in the Brain: The Example of Neurodevelopment Alterations upon Exposure In Utero to Synthetic Sex Hormones.Journal of xenobiotics · 2025Review
- Perinatal hypoxia-mediated neurodevelopment abnormalities in congenital heart disease mouse model.Molecular medicine (Cambridge, Mass.) · 2025Article
- Repeated Levonorgestrel Administration Impairs Cognitive Function via Glutamatergic Transmission and CaMKII-PKA-BDNF Signaling in the Hippocampus of Female Wistar Rats.Journal of experimental pharmacology · 2025Article
- Role of estrogen in sex differences in memory, emotion and neuropsychiatric disorders.Molecular biology reports · 2024Review
- Evodiamine suppresses endometriosis development induced by early EBV exposure through inhibition of ERβ.Frontiers in pharmacology · 2024Article
- Giftedness and atypical sexual differentiation: enhanced perceptual functioning through estrogen deficiency instead of androgen excess.Frontiers in endocrinology · 2024Review
- Exposure to Progestin 17-OHPC Induces Gastrointestinal Dysfunction through Claudin-1 Suppression in Female Mice with Increased Anxiety-Like Behaviors.Neuroendocrinology · 2024Article
- LMP1 mediates tumorigenesis through persistent epigenetic modifications and PGC1β upregulation.Oncology reports · 2023Article
- Effect of Resveratrol on Pregnancy, Prenatal Complications and Pregnancy-Associated Structure Alterations.Antioxidants (Basel, Switzerland) · 2023Review
- Editorial: Endocrinological factors for autism: prenatal biomarkers, early diagnosis and symptom treatment.Frontiers in endocrinology · 2023Article
- Effects of prenatal exposure to synthetic sex hormones on neurodevelopment: a biological mechanism.Frontiers in molecular neuroscience · 2023Review
- Hematopoietic stem cell transplantation ameliorates maternal diabetes-mediated gastrointestinal symptoms and autism-like behavior in mouse offspring.Annals of the New York Academy of Sciences · 2022Article
- Maternal diabetes-mediated RORA suppression contributes to gastrointestinal symptoms in autism-like mouse offspring.BMC neuroscience · 2022Article
- Maternal diabetes-mediated RORA suppression in mice contributes to autism-like offspring through inhibition of aromatase.Communications biology · 2022Article
- Diethylstilbestrol and autism.Frontiers in endocrinology · 2022Review
- Rethinking autism: the impact of maternal risk factors on autism development.American journal of translational research · 2022Review
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAutism spectrum disorder (ASD) is characterized by impairments in social communication and restricted or repetitive behaviors or interests. ASD is now diagnosed in more than one out of 100 children and is biased towards males by a ratio of at least 4:1. Many possible explanations and potential causative factors have been reported, such as genetics, sex, and environmental factors, although the detailed mechanisms of ASD remain unclear.
methodsThe dams were exposed through oral contraceptives to either vehicle control (VEH) alone, levonorgestrel (LNG) alone, ethinyl estradiol (EE) alone, or a combination of LNG/EE for 21 days during their pregnancy. The subsequent 10-week-old offspring were used for autism-like behavior testing, and the limbic tissues were isolated for analysis. In another experimental group, 8-week-old male offspring were treated by infusion of ERβ overexpression/knockdown lentivirus in the amygdala, and the offspring were analyzed after 2 weeks.
resultsWe show that prenatal exposure of either LNG alone or a LNG/EE combination, but not EE alone, results in suppression of ERβ (estrogen receptor β) and its target genes in the amygdala with autism-like behavior in male offspring, while there is a much smaller effect on female offspring. However, we find that there is no effect on the hippocampus and hypothalamus. Further investigation shows that ERβ suppression is due to LNG-mediated altered methylation on the ERβ promoter and results in tissue damage with oxidative stress and the dysfunction of mitochondria and fatty acid metabolism, which subsequently triggers autism-like behavior. Overexpression of ERβ in the amygdala completely restores LNG-induced ERβ suppression and autism-like behaviors in offspring, while ERβ knockdown mimics this effect, indicating that ERβ expression in the amygdala plays an important role in autism-like behavior development.
conclusionsWe conclude that prenatal levonorgestrel exposure induces autism-like behavior in offspring through ERβ suppression in the amygdala. To our knowledge, this is the first time the potential effect of oral contraceptives on the contribution of autism-like behavior in offspring has been discovered.
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