Maternal iron nutriture modulates placental development in a rat model of fetal alcohol spectrum disorder
| Autor: | George R. Flentke, Pamela J. Kling, Camille A. Kezer, Shane M. Huebner, Sze Ting Cecilia Kwan, Nipun Saini, Kaylee K. Helfrich, Susan M. Smith |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Health (social science) Offspring Alcohol Placental insufficiency Toxicology Biochemistry Article Proinflammatory cytokine 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Pregnancy Internal medicine Placenta medicine Animals Rats Long-Evans Inflammation Fetus Ethanol business.industry Iron Deficiencies Maternal Nutritional Physiological Phenomena General Medicine Iron deficiency medicine.disease Placentation Rats 030227 psychiatry Disease Models Animal Endocrinology medicine.anatomical_structure Neurology chemistry Fetal Alcohol Spectrum Disorders Cytokines Gestation Female business Iron Dietary 030217 neurology & neurosurgery |
| Zdroj: | Alcohol |
| ISSN: | 0741-8329 |
| DOI: | 10.1016/j.alcohol.2019.11.003 |
| Popis: | Prenatal alcohol exposure (PAE) causes developmental abnormalities known as fetal alcohol spectrum disorder (FASD). Maternal iron status modulates the severity of these defects in the offspring. Because the placenta is central in supporting fetal development, we investigated whether maternal iron status similarly modulates alcohol's effects in the placenta. We hypothesized that PAE causes placental insufficiency by decreasing placental weight and efficiency, and we hypothesized that these are worsened by maternal iron deficiency (ID) and alleviated by dietary iron fortification (IF). We also determined whether altered placental iron flux and inflammatory balance contribute to placental insufficiency. Pregnant Long-Evans rats consumed an iron-deficient (ID; 2-6 ppm), iron-sufficient (IS; 100 ppm), or iron-fortified (IF; 500 ppm) diet. Alcohol (5 g/kg body weight) or isocaloric maltodextrin (MD) was gavaged daily from gestational day (GD) 13.5-19.5. Placental outcomes were evaluated on GD20.5. PAE reduced fetal weight (p 0.0001), placental weight (p = 0.0324), and placental efficiency (p = 0.0043). PAE downregulated placental transferrin receptor (p = 0.0032); it also altered placental Il1b and Tnf expression and the Il6:Il10 ratio (p = 0.0337, 0.0300, and 0.0034, respectively) to generate a response favoring inflammation. ID-PAE further reduced fetal growth and placental efficiency and induced a heightened pro-inflammatory placental profile. IF did not rescue the alcohol-reduced fetal weight, but it normalized placental efficiency and decreased placental inflammation. These placental cytokines correlated with fetal and placental growth, and explained 45% of the variability in fetal weight and 20% of the variability in placental efficiency. In summary, alcohol induces placental insufficiency and is associated with a pro-inflammatory cytokine profile exacerbated by maternal ID and mitigated by maternal IF. Because the placenta is closely linked to intrauterine growth, the placental insufficiency reported here may correlate with the lower birth weights in a subgroup of individuals who experienced PAE. |
| Databáze: | OpenAIRE |
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