Maternal Serum Fractalkine Concentrations in Pregnancies Complicated by Fetal Growth Restriction

Sager, Ecem Berfun Toprak; Kale, İbrahim; Sager, Hakan; Özel, Ayşegül; Muhçu, Murat

doi:10.21613/gorm.2022.1342

Cited by 3 publications

(3 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies revealed that FKN might contribute to endometrial receptivity, implantation, and pregnancy (Kervancioglu Demirci et al, 2016; Machairiotis et al, 2021; Pap et al, 2020; Toprak Sager et al, 2022). It has also been described that FKN can modulate the inflammatory action of macrophages by altering the production of proinflammatory cytokines (Gong et al, 2021; Pandur et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

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

Pandur,

Pap,

Jánosa

et al. 2024

Cell Biology International

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Pandur,

Pap,

Jánosa

et al. 2024

Cell Biology International

View full text Add to dashboard Cite

show abstract

“…FKN level is elevated in the first trimester in the first trimester of pregnancy, but at high concentrations, it may associate with preeclampsia [41], although the serum level of FKN cannot be used as a prediction marker for preeclampsia [42]. Maternal serum FKN level may contribute to pregnancy complications like fetal growth restriction [43]. On the other hand, decreased expression of FKN in granulosa cells may contribute to elevated apoptosis and may be involved in abnormal oocyte maturation in patients with polycystic ovarian syndrome [44].…”

Section: Introductionmentioning

confidence: 99%

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

Pandur

Pap

Jánosa

et al. 2023

IJMS

View full text Add to dashboard Cite

Fractalkine (CX3CL1/FKN) is a unique chemokine belonging to the CX3C chemokine subclass. FKN exists in two forms: a membrane-bound form expressed by both endometrium cells and trophoblasts thought to be implicated in maternal–fetal interaction and a soluble form expressed by endometrium cells. Endometrium receptivity is crucial in embryo implantation and a complex process regulated by large numbers of proteins, e.g., cytokines, progesterone receptor (PR), SOX-17, prostaglandin receptors (PTGER2), and tissue inhibitors of metalloproteinases (TIMPs). It has also been reported that iron is important in fertility and affects the iron status of the mother. Therefore, iron availability in the embryo contributes to fertilization and pregnancy. In this study, we focused on the effect of iron deficiency on the secreted cytokines (IL-6, IL-1β, leukocyte inhibitory factor, TGF-β), chemokines (IL-8, FKN), and other regulatory proteins (bone morphogenic protein 2, activin, follistatin, PR, SOX-17, prostaglandin E2 receptor, TIMP2), and the modifying effect of FKN on the expression of these proteins, which may improve endometrium receptivity. Endometrial iron deficiency was mediated by desferrioxamine (DFO) treatment of HEC-1A cells. FKN was added to the cells 24 h and 48 h after DFO with or without serum for modelling the possible iron dependence of the alterations. Our findings support the hypothesis that FKN ameliorates the effects of anemia on the receptivity-related genes and proteins in HEC-1A cells by increasing the secretion of the receptivity-related cytokines via the fractalkine receptor (CX3CR1). FKN may contribute to cell proliferation and differentiation by regulating activin, follistatin, and BMP2 expressions, and to implantation by altering the protein levels of PR, SOX-17, PTGER2, and TIMP2. FKN mitigates the negative effect of iron deficiency on the receptivity-related genes and proteins of HEC-1A endometrium cells, suggesting its important role in the regulation of endometrium receptivity.

show abstract

“…It has been demonstrated that FKN is involved in the development of endometrial receptivity and embryo implantation, and it has a role in pregnancy [ 23 ], although its role in pregnancy is not fully understood [ 24 , 25 , 26 ]. In addition, it has been described that FKN may act as a regulator of iron metabolism in macrophages, microglia and endometrium cells [ 8 , 27 ].…”

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

View full text Add to dashboard Cite

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.

show abstract

Maternal Serum Fractalkine Concentrations in Pregnancies Complicated by Fetal Growth Restriction

Cited by 3 publications

References 24 publications

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

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

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

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

Contact Info

Product

Resources

About