Alcohol's Dysregulation of Maternal-Fetal IL-6 and p-STAT3 Is a Function of Maternal Iron Status

Autor: Kaylee K. Helfrich, Sharon E. Blohowiak, Susan M. Smith, Nipun Saini, George R. Flentke, Pamela J. Kling, Sze Ting Cecilia Kwan, Juna Abazi, Shane M. Huebner
Rok vydání: 2019
Předmět:
Zdroj: Alcohol Clin Exp Res
ISSN: 1530-0277
Popis: BACKGROUND Prenatal alcohol exposure (PAE) causes long-term growth and neurodevelopmental deficits that are worsened by maternal iron deficiency (ID). In our preclinical rat model, PAE causes fetal anemia, brain ID, and elevated hepatic iron via increased maternal and fetal hepcidin synthesis. These changes are normalized by a prenatal iron-fortified (IF) diet. Here, we hypothesize that iron status and PAE dysregulate the major upstream pathways that govern hepcidin production-EPO/BMP6/SMAD and IL-6/JAK2/STAT3. METHODS Pregnant, Long Evans rat dams consumed ID (2 to 6 ppm iron), iron-sufficient (IS, 100 ppm iron), or IF (500 ppm iron) diets and received alcohol (5 g/kg) or isocaloric maltodextrin daily from gestational days (GD) 13.5 to 19.5. Protein and gene expression were quantified in the 6 experimental groups at GD 20.5. RESULTS PAE did not affect Epo or Bmp6 expression, but reduced p-SMAD1/5/8/SMAD1/5/8 protein ratios in both IS and ID maternal and fetal liver (all p's
Databáze: OpenAIRE