Abstract：
Exposure to diisodecyl phthalate (DIDP) during early pregnancy may be a risk factor for depressive behavior in offspring. While ozone (O3) exposure also raises the probability of depressive behavior during the preceding DIDP-induced process. In the present study, we investigated the effects of prenatal exposure to DIDP and O3 on the development of depressive-like behavior in offspring mice. The study found that prenatal exposure to both DIDP and O3 significantly increased depressive-like behavior in the offspring mice compared to either DIDP or O3 alone. Prenatal exposure to DIDP and O3 obviously increased the levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol, and decreased the levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) in the brain tissues of offspring mice. Transcriptome analysis further revealed significant alterations in genes related to oxidative stress and TWIST1 (a helix-loop-helix transcription factor) in response to the combined exposure to DIDP and O3. HPA axis activation, dysregulation of neurodevelopmental factors, oxidative stress and TWIST1 involvement, collectively contributed to the development of depression-like behaviors in offspring mice following prenatal exposure to DIDP and O3. Moreover, the study also verified the potential role of oxidative stress using vitamin E as an antioxidant. The findings provide valuable evidence for the relationship between co-exposure to DIDP and O3 and depression, highlighting the importance of considering the combined effects of multiple environmental pollutants in assessing their impact on mental health outcomes.
摘要：
妊娠早期暴露于邻苯二甲酸二异癸酯（DIDP）可能是后代抑郁行为的危险因素。虽然臭氧（O3）暴露也会增加在前一过程中抑郁行为的可能性。在本研究中,我们调查了产前暴露于DIDP和O3对后代小鼠抑郁样行为发展的影响。研究发现，与单独的DIDP或O3相比，产前暴露于DIDP和O3会显着增加后代小鼠的抑郁样行为。产前暴露于DIDP和O3会明显增加促肾上腺皮质激素释放激素（CRH）的水平，促肾上腺皮质激素（ACTH）和皮质醇，并降低脑源性神经营养因子（BDNF）的水平，5-羟色胺（5-HT），后代小鼠脑组织中的多巴胺（DA）和去甲肾上腺素（NE）。转录组分析进一步显示，响应于DIDP和O3的联合暴露，与氧化应激和TWIST1（一种螺旋-环-螺旋转录因子）相关的基因发生了显着变化。HPA轴激活,神经发育因子失调，氧化应激和TWIST1参与，产前暴露于DIDP和O3后，共同促进了后代小鼠抑郁样行为的发展。此外，该研究还验证了使用维生素E作为抗氧化剂的氧化应激的潜在作用.研究结果为共同暴露于DIDP和O3与抑郁症之间的关系提供了有价值的证据，强调在评估多种环境污染物对心理健康结果的影响时，考虑多种环境污染物的综合影响的重要性。
