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Influences of serum from ozone-exposed pregnant rats in an in vitro model of implantation
Citation:
Stewart, E., C. Miller, J. Richards, M. Schladweiler, AND J. Dye. Influences of serum from ozone-exposed pregnant rats in an in vitro model of implantation. NC SOT, Durham, NC, October 30, 2017.
Impact/Purpose:
The aim of this study was to (1) determine if serum collected from pregnant rats shortly after ozone exposure would reduce migration and/or invasion of trophoblasts in an in vitro model of implantation, and (2) identify changes in serum factors of dams acutely post-exposure.
Description:
In our previous studies, ozone (O3) exposure during implantation [gestational day (GD) 5 and 6)] in rats resulted in intrauterine growth restriction (IUGR), suggesting impairment of implantation with exposure. The aim of this study was to (1) determine if serum collected from pregnant rats shortly after ozone exposure would reduce migration and/or invasion of trophoblasts in an in vitro model of implantation, and (2) identify changes in serum factors of dams acutely post-exposure. Pregnant Long-Evans rats were exposed to filtered air or ozone (0.4, 0.8, or 1.2 ppm) for four hours on GD5 and 6 with serum collected after exposure for assessment of metabolic and inflammatory endpoints. HTR-8/Svneo placental-derived, first trimester trophoblasts were treated with pooled serum from the 0.8 ppm O3-exposure group and tested for viability and migratory capacity using a scratch wound assay. HTR-8/Svneo cells treated for 16 hours with O3-serum showed significantly reduced viability (3-5%) compared to cells treated with air-serum at all concentrations examined. Likewise, cells treated with O3-serum had reduced wound closure (20%) when compared to treatment with control air-serum, suggesting that circulating factors in O3-serum impaired the migratory capacity of trophoblasts. Analysis of serum from air- and O3-exposed rats for revealed that O3 exposure resulted in a dose-dependent increase in serum glucose concentrations. Furthermore, O3 exposure caused small, dose dependent decreases in serum inflammatory cytokines (e.g., IFNγ, IL13, and IL6) compared to air controls. In summary, serum collected from dams after peri-implantation O3 exposure was bioactive in naïve trophoblasts and contained an altered metabolic and inflammatory profile. These findings suggest a role for O3-induced systemic factors in the impairment of placental health and vascular remodeling that can lead to IUGR. (Abstract does not reflect US EPA policy).