Background:Aromatase (CYP19) is a key enzyme in estrogens biosynthesis. In the mammary gland, CYP19 gene is expressed at low levels under the regulation of its I.4 promoter. In hormone-dependent breast cancer, fibroblast cells surrounding the tumor express increased levels of CYP19 mRNA due to a decrease of I.4 promoter activity and an increase of PII, I.3, and I.7 promoter activity. Little is known about the effects of environmental chemicals on the promoter-specific CYP19 expression.Objective:We aimed to determine the effects of two neonicotinoids (thiacloprid and imidacloprid) on promoter-specific CYP19 expression in Hs578t breast cancer cells and understand the signaling pathways involved.Methods:Hs578t cells were exposed to various signaling pathway stimulants or neonicotinoids for 24 h. Promoter-specific expression of CYP19 was determined by real-time quantitative polymerase chain reaction and catalytic activity of aromatase by tritiated water release assay.Results:To our knowledge, we are the first to demonstrate that the normal I.4 promoter and the breast cancer-relevant PII, I.3, and I.7 promoters of CYP19 are active in these cells. We found that the expression of CYP19 via promoters PII, I.3, and I.7 in Hs578t cells was, in part, dependent on the activation of two VEGF signaling pathways: mitogen-activated protein kinase (MAPK) 1/3 and phospholipase C (PLC). Exposure of Hs578t cells to environmental concentrations of imidacloprid and thiacloprid resulted in a switch in CYP19 promoter usage, involving inhibition of I.4 promoter activity and an increase of PII, I.3, and I.7 promoter-mediated CYP19 expression and aromatase catalytic activity. Greater effects were seen at lower concentrations. Our results suggest that thiacloprid and imidacloprid exert their effects at least partially by inducing the MAPK 1/3 and/or PLC pathways.Conclusions:We demonstrated in vitro that neonicotinoids may stimulate a change in CYP19 promoter usage similar to that observed in patients with hormone-dependent breast cancer. https://doi.org/10.1289/EHP2698

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Objectives Mental health and neurocognitive conditions are important causes of hospitalization among immigrants, though patterns may vary by immigrant category, world region of origin, and time since arrival in Canada. This study uses linked administrative data to explore differences in mental health hospitalization rates between immigrants and individuals born in Canada. Methods Hospital records from the Discharge Abstract Database and the Ontario Mental Health Reporting System for 2011 to 2017 were linked to the 2016 Longitudinal Immigrant Database and to Statistics Canada’s 2011 Canadian Census Health and Environment Cohort. Age-standardized hospitalization rates for mental health–related conditions (ASHR-MHs) were derived for immigrants and the Canadian-born population. ASHR-MHs overall and for leading mental health conditions were compared between immigrants and the Canadian-born population, stratified by sex and selected immigration characteristics. Quebec hospitalization data were not available. Results Overall, immigrants had lower ASHR-MHs compared to the Canadian-born population. Mood disorders were leading causes of mental health hospitalization for both cohorts. Psychotic, substance-related, and neurocognitive disorders were also leading causes of mental health hospitalization, although there was variation in their relative importance between subgroups. Among immigrants, ASHR-MHs were higher among refugees and lower among economic immigrants, those from East Asia, and those who arrived in Canada most recently. Conclusion Differences in hospitalization rates among immigrants from various immigration streams and world regions, particularly for specific types of mental health conditions, highlight the importance of future research that incorporates both inpatient and outpatient mental health services to further understand these relationships.