Maternal undernourishment stimulates fetuin‐B and impairs placental development

Abstract

Background and AimsLow birth weight (LBW) significantly increases the risk for multiple diseases, including cardiovascular and kidney diseases. Low birth weight can be caused by a variety of factors, including maternal undernourishment (MUN) during pregnancy. In our study here, we investigated the effects of MUN on the developing placenta, with particular focus on the role of oxidative stress and fetuin‐B in placental impairment.MethodsUsing a mouse model of MUN to generate LBW offspring, in which the pregnant mother consumes reduced total calories and protein during gestation, we examined placental vascularization, vascular reactivity, and blood perfusion using immunofluorescence, myograph, and laser‐doppler flowmetry, respectively. We further examined placental pathology during MUN and pharmacological intervention through histology, immunofluorescence staining and immunoblotting. Trophoblast cell cultures were also used in experiments.ResultsWe observed reduced vascular density, vascular reactivity and blood perfusion in the placenta during MUN, along with a reduction in total placental trophoblasts. Further analysis revealed that MUN significantly increases the expression and secretion of the small protein fetuin‐B in the placenta. Treatment of trophoblasts with fetuin‐B increased the activity of NF‐kB in these cells, while also stimulating their generation of reactive oxygen species. Subsequently, fetuin‐B effectively reduced trophoblast quantity by impairing their proliferative expansion, stimulating their apoptosis, and reducing their differentiation. Treatment of MUN pregnant mothers with antioxidants improved placental vascular function and helped preserve placental trophoblast pools.ConclusionMUN upregulates fetuin‐B and oxidative stress in the placenta, effects which consequently impair placental development and vascular function.