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Additional file 3: Fig. S3. hUMSCs overexpressed TSG-6 in response to the inflammatory cytokine TNF-α. The relative expression levels of TSG-6 mRNA were determined by RT-qPCR and representative protein bands and corresponding grayscale values of TSG-6 were performed by western blotting. All data are represented as means ± SD of at least 3 independent experiments and compared by t-test. **p < 0.01 versus control.

Additional file 2: Fig. S2. The expression of the TSG-6 was knocked down using TSG-6-shRNA lentivirus. The relative mRNA expression levels of TSG-6 mRNA were determined by RT-qPCR and representative protein bands and corresponding grayscale values of TSG-6 were determined by western blotting. All data are represented as means ± SD of at least 3 independent experiments and compared by one-way ANOVA, followed by the Tukey’s post hoc test. **p < 0.01 versus control or control shRNA.

Additional file 1: Fig. S1. Surface marker expression in hUMSCs. hUMSCs were confirmed by flow cytometry analysis following three passages as positive for CD73 (100%), CD105 (99.96%), and CD90 (100%), and negative for CD45 (0.06%), HLA-DR (0.06%), CD34 (0.01%), CD11b (0.01%), and CD19 (0.00%).

A novel Ag6Si2O7/CNTs composite photocatalyst was prepared by in-situ precipitation and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive spectrosc...

Background Recent literatures indicate that maternal hormone exposure is a risk factor for autism spectrum disorder (ASD). We hypothesize that prenatal progestin exposure may counteract the neuroprotective effect of estrogen and contribute to ASD development, and we aim to develop a method to ameliorate prenatal progestin exposure-induced autism-like behavior. Methods Experiment 1: Prenatal progestin exposure-induced offspring are treated with resveratrol (RSV) through either prenatal or postnatal exposure and then used for autism-like behavior testing and other biomedical analyses. Experiment 2: Prenatal norethindrone (NET) exposure-induced offspring are treated with ERβ knockdown lentivirus together with RSV for further testing. Experiment 3: Pregnant dams are treated with prenatal NET exposure together with RSV, and the offspring are used for further testing. Results Eight kinds of clinically relevant progestins were used for prenatal exposure in pregnant dams, and the offspring showed decreased ERβ expression in the amygdala with autism-like behavior. Oral administration of either postnatal or prenatal RSV treatment significantly reversed this effect with ERβ activation and ameliorated autism-like behavior. Further investigation showed that RSV activates ERβ and its target genes by demethylation of DNA and histone on the ERβ promoter, and then minimizes progestin-induced oxidative stress as well as the dysfunction of mitochondria and lipid metabolism in the brain, subsequently ameliorating autism-like behavior. Conclusions We conclude that resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERβ activation. Our data suggest that prenatal progestin exposure is a strong risk factor for autism-like behavior. Many potential clinical progestin applications, including oral contraceptive pills, preterm birth drugs, and progestin-contaminated drinking water or seafood, may be risk factors for ASD. In addition, RSV may be a good candidate for clinically rescuing or preventing ASD symptoms in humans, while high doses of resveratrol used in the animals may be a potential limitation for human application. Electronic supplementary material The online version of this article (10.1186/s13229-018-0225-5) contains supplementary material, which is available to authorized users.

Background Autism 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. Methods The 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. Results We 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. Conclusions We 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. Electronic supplementary material The online version of this article (doi:10.1186/s13229-017-0159-3) contains supplementary material, which is available to authorized users.