Objective: To investigate the effects of developmental exposure to DEHP on learning and memory of mice. Methods: Male littermates of ICR mice randomly assigned to five experimental groups (n=14 for each condition) on PND4 to receive distilled water, vehicle and 10, 50 and 200 mg/ (kg·d) DEHP from PND5 to PND38 by gavage, weighing and recording body weight of mice. Open field task were conducted on PND 26 and Morris water maze task were begun from PND30 to PND 37 to evaluate spontaneous exploration activity and emotion, spatial learning and memory performance of pubertal mice, respectively. On PND39, all animals were killed and hippocampi were isolated on ice, then total proteins of hippocampus were extracted, followed by determining the expression of PSD95 and synapsin I by western blotting. Results: 200 mg/ (kg·d) DEHP significantly reduced the growth of body weight of mice and the time staying in the central area in open field, prolonged the time searching the hidden platform in Morris water maze (P<0.05) . 50 mg/ (kg·d) DEHP didn’t change the growth of body weight and the emotion (P>0.05) , but reduced the percent of time and distance in the target quadrant during the probe trial of mice in Morris water maze (P<0.05) . The results of western blotting showed that DEHP significantly reduced the expression of PSD95 in hippocampus of mice with all dose groups (P<0.01) , but only 200 mg/ (kg·d) DEHP reduced the expression of synapsin I (P<0.05) . Conclusion Developmental exposure to DEHP can damage the development of synapse in hippocampus, adversely impacting spatial memory performance of mice at a dose that are insufficient to significantly influence the general development and result in anxiety.

Objective: The present study was represented by di-(2-ethylhexyl) phthalate (DEHP), to explore the role of thyroid hormones (THs) disruption in the connection of placenta and neurodevelopmental toxicity. Methods: During fetal mice neural tube closed (pregnancy 9.5 days, E9.5d) to begin synthesis of THs (E15.5 d), all pregnant mice were administered with different concentration of DEHP (0、10、50、200 mg/kg) by gavage once a day(10 mice per group). All pregnant mice were conducted with BrdU administration in E14d by subcutaneous injection. Seven pregnant mice from each group were scarified after anesthesia in E15.5 d, serum and amniotic fluid were collected to determinate the levels of THs(T₃, T₄, FT₃ and FT₄) by the automatic biochemical analyzer, detecting fetal mice placental protein expression of monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptide 1C1 (OATP1C1) and deiodinaseⅡ&Ⅲ (DIO₂, DIO₃) by Western blot. Each group of the remaining three pregnant mices were killed after anesthesia in E18d, take the male fetal brain, BrdU immunohistochemistry was used to detect the proliferation and migration of fetal brain cortical neurons. Results: There was no abnormalities in diet, water intake, body weight and general activity of pregnant mice in each treatment group, and there were no difference in the general physiolo. Results There was no abnormalities in diet, water intake, body weight and general activity of pregnant mice in each treatment group, and there were no difference in the general physiological development status of body weight, brain weight, brain body ratio between the mice of each group. There was no statistically significant differences in serum T₃, T₄, FT₃, FT₄ and amniotic fluid FT₄ in pregnant mice of each group (P>0.05), Compared with the control group, the FT₃ levels in the amniotic fluid of the DEHP 50 and 200 mg/kg groups were significantly decreased(P<0.05). Compared with the control group, the placental MCT8 and DIO₂ protein levels of male fetal mice in the DEHP 50 and 200 mg/kg group decreased, and the level of OATP1C1 protein in 200 mg/kg group decreased(P<0.05), and there was no statistically significant difference in DIO₃ protein levels among all groups (P>0.05). Compared with the control group, the number of BrdU positive cells in the cerebral cortex of male mice in DEHP 200 mg/kg group decreased, 56.5% was distributed in VZ-SVZ layer, and the percentage of BrdU positive cells in the IZ layer of 50 mg/kg group increased (P<0.05). Conclusion DEHP 50, 200 mg/kg may affect the proliferation and migration of neural cells in the developing brain, which may be related to its interference with thyroid hormone by placental transport.

Objective To explore the effect of BDNF pathway on lambda-cyhalothrin interfering estrogen promoting the expression of PSD95 in hippocampus neurons.Methods HT22 cell line were used to,treating with lambda-cyhalothrin (LCT,50 μmol/L),17 β-Estradiol (E2,10 nmol/L),LCT (50 μmol/L) +TrkB FC (20 μg/ml),E2 (10 nmol/L) +TrkB FC (20 μg/ml),LCT(50 μmol/L) +ICI182 780 (1 μmol/L),E2 (10 nmol/L)+ ICI182 780 (1 μmol/L),LCT (50 μmol/L)+E2 (10 nmol/L) for 24 h.MTT kit was used to detect cell viability.Post-synaptic Density 95 protein expression was measured by western blot.ELISA assay was used to detect the level of brain derived neurotrophic factor (BDNF) of culture supernatant and cell.Results Campared to Sham,LCT or E2 could promote the expression of PSD95 LCT+ICI could reduce the expresion of BDNF (P＜0.05),campared to LCT,LCT+TrkB FC could reduce the expression of PSD95 and LCT+ICI cound reduce the expresion of BDNF (P＜0.05),campared to E2,E2+TrkB FC could reduce the expression of PSD95 and E2+ICI could reduce the expression of BDNF (P＜0.05),campared to E2,LCT+ E2 could reduce the expression of PSD95 and BDNF (P＜ 0.05).Conclusion BDNF pathway plays a key role in E2 promoting the expression of PSD95 in neural cells.Although LCT alone has a similar effect on E2.LCT could disrupt the promotion of E2 on PSD95 expression via BDNF pathway.

Objective To explore the effect of BDNF pathway on lambda-cyhalothrin interfering estrogen promoting the expression of PSD95 in hippocampus neurons.Methods HT22 cell line were used to,treating with lambda-cyhalothrin (LCT,50 μmol/L),17 β-Estradiol (E2,10 nmol/L),LCT (50 μmol/L) +TrkB FC (20 μg/ml),E2 (10 nmol/L) +TrkB FC (20 μg/ml),LCT(50 μmol/L) +ICI182 780 (1 μmol/L),E2 (10 nmol/L)+ ICI182 780 (1 μmol/L),LCT (50 μmol/L)+E2 (10 nmol/L) for 24 h.MTT kit was used to detect cell viability.Post-synaptic Density 95 protein expression was measured by western blot.ELISA assay was used to detect the level of brain derived neurotrophic factor (BDNF) of culture supernatant and cell.Results Campared to Sham,LCT or E2 could promote the expression of PSD95 LCT+ICI could reduce the expresion of BDNF (P＜0.05),campared to LCT,LCT+TrkB FC could reduce the expression of PSD95 and LCT+ICI cound reduce the expresion of BDNF (P＜0.05),campared to E2,E2+TrkB FC could reduce the expression of PSD95 and E2+ICI could reduce the expression of BDNF (P＜0.05),campared to E2,LCT+ E2 could reduce the expression of PSD95 and BDNF (P＜ 0.05).Conclusion BDNF pathway plays a key role in E2 promoting the expression of PSD95 in neural cells.Although LCT alone has a similar effect on E2.LCT could disrupt the promotion of E2 on PSD95 expression via BDNF pathway.

Sex reversal, representing extraordinary sexual plasticity during the life cycle, not only triggers reproduction in animals but also affects reproductive and endocrine system-related diseases and cancers in humans. Sex reversal has been broadly reported in animals; however, an integrated resource hub of sex reversal information is still lacking. Here, we constructed a comprehensive database named ASER (Animal Sex Reversal) by integrating sex reversal-related data of 18 species from teleostei to mammalia. We systematically collected 40,018 published papers and mined the sex reversal-associated genes (SRGs), including their regulatory networks, from 1611 core papers. We annotated homologous genes and computed conservation scores for whole genomes across the 18 species. Furthermore, we collected available RNA-seq datasets and investigated the expression dynamics of SRGs during sex reversal or sex determination processes. In addition, we manually annotated 550 in situ hybridization (ISH), fluorescence in situ hybridization (FISH), and im-munohistochemistry (IHC) images of SRGs from the literature and described their spatial expression in the gonads. Collectively, ASER provides a unique and integrated resource for researchers to query and reuse organized data to explore the mechanisms and applications of SRGs in animal breeding and human health. The ASER database is publicly available at http://aser.ihb.ac.cn/.