Maternal iron deficiency perturbs embryonic cardiovascular development

Kalisch-Smith, Jacinta I.; Ved, Nikita; Szumska, Dorota; Munro, Jacob E.; Troup, Michael; Se, Harris; Jacquemot, Aimée; Jj, Miller; Em, Stuart; Wolna, Magda; Hardman, Emily; F, Prin; Lana-Elola, Eva; Aoidi, Rifdat; Fisher, Elizabeth; Vlj, Tybulewicz; Mohun, TJ; Lakhal‐Littleton, Samira; Giannoulatou, Eleni; Db, Sparrow

doi:10.1101/2020.08.03.230615

Cited by 2 publications

(1 citation statement)

References 98 publications

(130 reference statements)

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“…Analysis of an NTD cohort did suggest that both iron and magnesium levels were significantly reduced in NTD cases; thus, the interplay between iron and magnesium should also be considered in NTDs (Groenen et al, 2004). Moreover, iron deficiency in mouse embryos can result in congenital heart defects and this was associated with increased RA signaling (Kalisch‐Smith et al, 2021). Perhaps, iron deficiency in the Fpn1 hypomorphs may lead to an increase in RA.…”

Section: The Case For Ra Zinc and Iron Imbalance In Ntdsmentioning

confidence: 99%

Micronutrient imbalance and common phenotypes in neural tube defects

Kakebeen

Niswander

2021

Genesis

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Neural tube defects (NTDs) are among the most common birth defects, with a prevalence of close to 19 per 10,000 births worldwide. The etiology of NTDs is complex involving the interplay of genetic and environmental factors. Since nutrient deficiency is a risk factor and dietary changes are the major preventative measure to reduce the risk of NTDs, a more detailed understanding of how common micronutrient imbalances contribute to NTDs is crucial. While folic acid has been the most discussed environmental factor due to the success that population-wide fortification has had on prevention of NTDs, folic acid supplementation does not prevent all NTDs. The imbalance of several other micronutrients has been implicated as risks for NTDs by epidemiological studies and in vivo studies in animal models. In this review, we highlight recent literature deciphering the multifactorial mechanisms underlying NTDs with an emphasis on mouse and human data. Specifically, we focus on advances in our understanding of how too much or too little retinoic acid, zinc, and iron alter gene expression and cellular processes contributing to the pathobiology of NTDs. Synthesis of the discussed literature reveals common cellular phenotypes found in embryos with NTDs resulting from several micronutrient imbalances. The goal is to combine knowledge of these common cellular phenotypes with mechanisms underlying micronutrient imbalances to provide insights into possible new targets for preventative measures against NTDs.

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Section: The Case For Ra Zinc and Iron Imbalance In Ntdsmentioning

confidence: 99%

Micronutrient imbalance and common phenotypes in neural tube defects

Kakebeen

Niswander

2021

Genesis

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Maternal iron deficiency impacts the placental arterial network

Kalisch-Smith

Morris

et al. 2021

Preprint

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Placental vascular gene networks in mammals have been largely unexplored due to a lack of well validated molecular markers to identify them. This is required to study how they form in development, and how they are impacted by embryonic or maternal defects, which in-turn adversely affects the forming heart and vasculature. Such defects are known to be a consequence of maternal iron deficiency (ID), the most common nutrient deficiency world-wide. Here we employed marker analysis to characterise the arterial/arteriole and venous/venule endothelial cells (ECs) during normal placental development, and in the context of maternal ID. We reveal for the first time that placental ECs are unique compared with their embryonic counterparts. In the developing embryo, arterial ECs express Neuropilin1 (Nrp1), Delta-like ligand 4 (Dll4) and Notch1, while developing venous ECs express Neuropilin2 (Nrp2), Apj (Aplnr) and Ephrinb4 (Ephb4). However, in the E15.5 placenta, Nrp1 and Notch1 were restricted to arteries, but not continuing arteriole ECs. The arterial tree exclusively expressed Dll4. Nrp2 showed pan-EC expression at E15.5, while Ephb4 was not present at this stage. However, we found the placental venous vascular tree could be distinguished from the arterial tree by high versus low Endomucin (EMCN) and Apj (Aplnr) expression respectively. Using EMCN, we reveal that the placental arterial, but not venous, vascular tree is adversely impacted by maternal ID, with reduced area, total length and number of junctions of all vessels without affecting the EMCN high vessels. Defects to the embryonic cardiovascular system can therefore have a significant impact on blood flow delivery and expansion of the placental arterial tree.

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Maternal iron deficiency perturbs embryonic cardiovascular development

Cited by 2 publications

References 98 publications

Micronutrient imbalance and common phenotypes in neural tube defects

Micronutrient imbalance and common phenotypes in neural tube defects

Maternal iron deficiency impacts the placental arterial network

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