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- W2905808704 abstract "To assess the fetal neuroprotective potential of 17-hydroxyprogesterone (17OHP) and identify mechanisms for its benefit, using a novel mouse model of chronic maternal systemic inflammation. Using a mouse model of chronic maternal systemic inflammation involving daily intraperitoneal (IP) injections of 1mg IL-1β to CD-1 timed-pregnant dams from E15 to E18, we have previously shown that IL-1β administration results in impaired pup survival and neurodevelopmental outcomes, along with significant placental upregulation of NFκB2 and CXCL11 compared to controls. In our current experiment, CD-1 timed-pregnant dams were randomly assigned to three groups: IP phosphate buffered saline (PBS, n=8), IP IL-1β (n=13), or IP IL-1β + subcutaneous 17OHP (IL-1β/P, n=10). PBS or IL-1β was administered daily from E15 to E18 with 17OHP injected 1h prior to IL-1β in randomly selected dams. Fetal brains and placentas of E18 embryos were collected 6h after final IL-1β injections and individual qPCR analyses were carried out for the following immune markers: CCL2, CCL3, CXCL9, CXCL10, CXCL11, NFκB1, NFκB2, IL-1β, IL-6, and TNFα. Additionally, flow cytometry of E18 placentas was carried out for CD3+CD4+ and CD3+CD8+ cells. Pups that did not undergo tissue harvesting underwent neurodevelopmental assessment at PND5 and PND9. Data were analyzed using χ2 test and ANOVA, as appropriate. IL-1β/P pups exhibited significantly improved performance on neurodevelopmental assessment compared IL-1β pups (Figure 1). QPCR analysis of immune markers in placentas revealed that 17OHP significantly reduced NFκ B1 (P = .0352) with a non-significant trend towards lower levels of IL-6 and NFκB2 (Figure 2). Placental CD4/CD8 ratios were significantly decreased in IL-1β/P pups compared to IL-1β pups (P < .05). 17OHP improves offspring neurodevelopment in pregnant dams exposed to IL-1β-initiated chronic inflammation. Placental immunomodulation via reduction in expression of transcription factors involved in cellular responses to inflammation and reduction in inflammatory cytokines are potential mechanisms by which 17OHP confers a beneficial immunomodulatory effect on the placenta that can be neuroprotective and warrants further investigation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)" @default.
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- W2905808704 date "2019-01-01" @default.
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- W2905808704 title "535: 17-hydroxyprogesterone decreases adverse perinatal neurologic outcomes via placental immunomodulation of IL-1β pathway" @default.
- W2905808704 doi "https://doi.org/10.1016/j.ajog.2018.11.557" @default.
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