Maternal Iron Deficiency Alters Trophoblast Differentiation and Placental Development in Rat Pregnancy.

Iron deficiency, which occurs when iron demands chronically exceed intake, is prevalent in pregnant women. Iron deficiency during pregnancy poses major risks for the baby, including fetal growth restriction and long-term health complications. The placenta serves as the interface between a pregnant mother and her baby, and it ensures adequate nutrient provisions for the fetus. Thus, maternal iron deficiency may impact fetal growth and development by altering placental function. We used a rat model of diet-induced iron deficiency to investigate changes in placental growth and development. Pregnant Sprague-Dawley rats were fed either a low-iron or iron-replete diet starting 2 weeks before mating. Compared with controls, both maternal and fetal hemoglobin were reduced in dams fed low-iron diets. Iron deficiency decreased fetal liver and body weight, but not brain, heart, or kidney weight. Placental weight was increased in iron deficiency, due primarily to expansion of the placental junctional zone. The stimulatory effect of iron deficiency on junctional zone development was recapitulated in vitro, as exposure of rat trophoblast stem cells to the iron chelator deferoxamine increased differentiation toward junctional zone trophoblast subtypes. Gene expression analysis revealed 464 transcripts changed at least 1.5-fold (P < 0.05) in placentas from iron-deficient dams, including altered expression of genes associated with oxygen transport and lipoprotein metabolism. Expression of genes associated with iron homeostasis was unchanged despite differences in levels of their encoded proteins. Our findings reveal robust changes in placentation during maternal iron deficiency, which could contribute to the increased risk of fetal distress in these pregnancies.

Omics Approaches to Study Formation and Function of Human Placental Syncytiotrophoblast.

Proper development of the placenta is vital for pregnancy success. The placenta regulates exchange of nutrients and gases between maternal and fetal blood and produces hormones essential to maintain pregnancy. The placental cell lineage primarily responsible for performing these functions is a multinucleated entity called syncytiotrophoblast. Syncytiotrophoblast is continuously replenished throughout pregnancy by fusion of underlying progenitor cells called cytotrophoblasts. Dysregulated syncytiotrophoblast formation disrupts the integrity of the placental exchange surface, which can be detrimental to maternal and fetal health. Moreover, various factors produced by syncytiotrophoblast enter into maternal circulation, where they profoundly impact maternal physiology and are promising diagnostic indicators of pregnancy health. Despite the multifunctional importance of syncytiotrophoblast for pregnancy success, there is still much to learn about how its formation is regulated in normal and diseased states. 'Omics' approaches are gaining traction in many fields to provide a more holistic perspective of cell, tissue, and organ function. Herein, we review human syncytiotrophoblast development and current model systems used for its study, discuss how 'omics' strategies have been used to provide multidimensional insights into its formation and function, and highlight limitations of current platforms as well as consider future avenues for exploration.