Fractalkine Improves the Expression of Endometrium Receptivity-Related Genes and Proteins at Desferrioxamine-Induced Iron Deficiency in HEC-1A Cells

Pandur, Edina; Pap, Ramóna; Jánosa, Gergely; Horváth, Adrienn; Sipos, Katalin

doi:10.3390/ijms24097924

Cited by 5 publications

(6 citation statements)

References 74 publications

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“…The HEC-1A cells express endometrial cell surface markers and adhesion molecules, such as intercellular adhesion molecules (ICAM), mucin-1, moesin and ezrin, and secrete tissue inhibitors of matrix metalloproteinases [ 32 , 33 , 34 ]. HEC-1A cells also express both estrogen and progesterone receptors, as well as cytokines [ 28 , 32 , 33 ]. According to the gene expression profile, HEC-1A cells represent the phenotype of luminal or glandular epithelial cells [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

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The Role of Fractalkine in the Regulation of Endometrial Iron Metabolism in Iron Deficiency

Pandur

Pap

Jánosa

et al. 2023

IJMS

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Iron is a crucial element in the human body. Endometrial iron metabolism is implicated in endometrium receptivity and embryo implantation. Disturbances of the maternal as well as the endometrial iron homeostasis, such as iron deficiency, can contribute to the reduced development of the fetus and could cause an increased risk of adverse pregnancy outcomes. Fractalkine is a unique chemokine that plays a role in the communication between the mother and the fetus. It has been demonstrated that FKN is involved in the development of endometrial receptivity and embryo implantation, and it functions as a regulator of iron metabolism. In the present study, we examined the effect of FKN on the iron metabolism of HEC-1A endometrial cells in a state of iron deficiency mediated by desferrioxamine treatment. Based on the findings, FKN enhances the expression of iron metabolism-related genes in iron deficiency and modifies the iron uptake via transferrin receptor 1 and divalent metal transporter-1, and iron release via ferroportin. FKN can activate the release of iron from heme-containing proteins by elevating the level of heme oxygenase-1, contributing to the redistribution of intracellular iron content. It was revealed that the endometrium cells express both mitoferrin-1 and 2 and that their levels are not dependent on the iron availability of the cells. FKN may also contribute to maintaining mitochondrial iron homeostasis. FKN can improve the deteriorating effect of iron deficiency in HEC-1A endometrium cells, which may contribute to the development of receptivity and/or provide iron delivery towards the embryo.

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Section: Discussionmentioning

confidence: 99%

“…In addition, it has been described that FKN may act as a regulator of iron metabolism in macrophages, microglia and endometrium cells [ 8 , 27 ]. Recent findings revealed that FKN improves the expression of receptivity-related genes in iron deficiency [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Fractalkine in the Regulation of Endometrial Iron Metabolism in Iron Deficiency

Pandur

Pap

Jánosa

et al. 2023

IJMS

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“…Additional research also underscores the significance of iron balance within both the endometrium and the embryo, suggesting this balance plays a crucial role in the endometrium's receptivity to an embryo and the subsequent implantation process [49][50][51][52][53]. There is promising research regarding Fractalkine (FKN) [363,364]. It has been found that FKN mitigates the negative impacts of iron deficiency on the receptivity-related genes and proteins in human endometrial carcinoma cells HEC-1A [363].…”

Section: Ironmentioning

confidence: 99%

“…There is promising research regarding Fractalkine (FKN) [363,364]. It has been found that FKN mitigates the negative impacts of iron deficiency on the receptivity-related genes and proteins in human endometrial carcinoma cells HEC-1A [363].…”

Section: Ironmentioning

confidence: 99%

Minerals and the Menstrual Cycle: Impacts on Ovulation and Endometrial Health

Kapper,

Oppelt,

Ganhör

et al. 2024

Nutrients

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The role of minerals in female fertility, particularly in relation to the menstrual cycle, presents a complex area of study that underscores the interplay between nutrition and reproductive health. This narrative review aims to elucidate the impacts of minerals on key aspects of the reproductive system: hormonal regulation, ovarian function and ovulation, endometrial health, and oxidative stress. Despite the attention given to specific micronutrients in relation to reproductive disorders, there is a noticeable absence of a comprehensive review focusing on the impact of minerals throughout the menstrual cycle on female fertility. This narrative review aims to address this gap by examining the influence of minerals on reproductive health. Each mineral’s contribution is explored in detail to provide a clearer picture of its importance in supporting female fertility. This comprehensive analysis not only enhances our knowledge of reproductive health but also offers clinicians valuable insights into potential therapeutic strategies and the recommended intake of minerals to promote female reproductive well-being, considering the menstrual cycle. This review stands as the first to offer such a detailed examination of minerals in the context of the menstrual cycle, aiming to elevate the understanding of their critical role in female fertility and reproductive health.

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“…Moreover, iron availability acts as a regulatory factor of endometrial receptivity as well as embryo implantation. Recent findings underlie the importance of iron in the expression of receptivity-related genes (Pandur et al, 2023).…”

Section: Introductionmentioning

confidence: 96%

Regulation of iron metabolism in HEC‐1A endometrium cells by macrophage‐derived factors and fractalkine

Pandur,

Pap,

Jánosa

et al. 2024

Cell Biology International

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Macrophages in the endometrium promote receptivity and implantation by secreting proinflammatory cytokines and other factors like fractalkine (FKN). Macrophages are closely linked to regulating iron homeostasis and can modulate iron availability in the tissue microenvironment. It has been revealed that the iron metabolism of the mother is crucial in fertility. Iron metabolism is strictly controlled by hepcidin, the principal iron regulatory protein. The inflammatory cytokines can modulate hepcidin synthesis and, therefore, the iron metabolism of the endometrium. It was proven recently that FKN, a unique chemokine, is implicated in maternal–fetal communication and may contribute to endometrial receptivity and implantation. In the present study, we investigated the effect of activated THP‐1 macrophages and FKN on the iron metabolism of the HEC‐1A endometrial cells. We established a noncontact coculture with or without recombinant human FKN supplementation to study the impact of the macrophage‐derived factors and FKN on the regulation of hepcidin synthesis and iron release and storage of endometrial cells. Based on our findings, the conditioned medium of the activated macrophages could modify hepcidin synthesis via the nuclear factor kappa‐light‐chain‐enhancer of activated B cells, the signal transducer and activator of transcription 3, and the transferrin receptor 2/bone morphogenetic protein 6/suppressor of mothers against decapentaplegic 1/5/8 signaling pathways, and FKN could alter this effect on the endometrial cells. It was also revealed that the conditioned macrophage medium and FKN modulated the iron release and storage of HEC‐1A cells. FKN signaling may be involved in the management of iron trafficking of the endometrium by the regulation of hepcidin. It can contribute to the iron supply for fetal development at the early stage of the pregnancy.

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Fractalkine Improves the Expression of Endometrium Receptivity-Related Genes and Proteins at Desferrioxamine-Induced Iron Deficiency in HEC-1A Cells

Cited by 5 publications

References 74 publications

The Role of Fractalkine in the Regulation of Endometrial Iron Metabolism in Iron Deficiency

The Role of Fractalkine in the Regulation of Endometrial Iron Metabolism in Iron Deficiency

Minerals and the Menstrual Cycle: Impacts on Ovulation and Endometrial Health

Regulation of iron metabolism in HEC‐1A endometrium cells by macrophage‐derived factors and fractalkine

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