Experimental Animal Nutrition
Objectives : The teratogenic effects of alcohol differ among individuals, and maternal nutriture may contribute to these differences. In this regard, our group has shown that maternal iron deficiency (ID) exacerbates alcohol’s toxicity on fetal development, and maternal iron fortification (IF) improves the poor developmental outcomes associated with prenatal alcohol exposure (PAE). Although the interactive effects of iron and PAE in fetus have been examined, their effects in placenta are less clear. Here, we sought to determine the effects of iron and PAE on placental cytokines that affect nutrient supply efficiency. We hypothesized that ID-PAE impairs placental and fetal growth, and alters placental cytokine expression to favor a pro-inflammatory profile; maternal IF attenuates some of these outcomes.
Methods : We fed pregnant rats an ID (2-6 ppm), iron-sufficient (100 ppm) or IF (500 ppm) diet throughout gestation. From gestational day (G) 13.5-19.5, we gavaged them with alcohol (5g/kg BW) or isocaloric control (maltodextrin, MD). We weighed the placentas and fetuses on G20.5, and quantified placental cytokine expression using qPCR. Data were analyzed by mixed linear model and 2-way ANOVA.
Results : As expected, fetal weight, placental weight and placental efficiency were lower (P < 0.05) in response to PAE compared to MD. We found that PAE altered the expression of IL-1β, TNF-α and IL-10 (P = 0.034, 0.030, 0.09, respectively), but not IFN-γ, IL-6 or IL-4, suggesting a selective effect of alcohol on placental cytokine expression. Maternal ID worsened these outcomes such that ID-PAE had the lowest fetal weight and placental efficiency and a heightened pro-inflammatory placental profile. Maternal IF normalized the alcohol-reduced placental efficiency by modulating placental cytokines to enhance nutrient transport. However, it didn’t fully rescue fetal weight. Nevertheless, these cytokines were correlated with and explained 45% variability in fetal weight in this PAE model.
Conclusions : These data provide insights into how iron and alcohol interact to alter placental functions and fetal growth. Further, the cytokines reported in this study may potentially be used as diagnostic markers to identify individuals who are prenatally exposed to alcohol.
Funding Sources :
NIH/NIAAA F32-AA027121 (STCK), R01-AA22999 (SMS)