Folate transporter expression in placenta from pregnancies complicated with birth defects

Reza-López, Sandra A.; Sánchez‐Ramírez, Blanca; Guerrero-Salgado, Fabiola; Chávez-Corral, Dora Virginia; Levario-Carrillo, Margarita

doi:10.1002/bdr2.1356

Cited by 9 publications

(6 citation statements)

References 20 publications

(25 reference statements)

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“…Contrary to our hypothesis, we found no differences in semi‐quantitative assessments of placental folate transporter protein localization or expression (for FRα, PCFT, and RFC) across study groups, and no associations between placental folate transporter expression and birthweight. Our findings are inconsistent with previous studies from India and Mexico, which have reported upregulated FRα and RFC expression in placentae from fetuses with NTDs, 20 and upregulated PCFT expression in placentae from fetuses with congenital anomalies (including, but not limited to, NTDs) 43 . India does not have mandatory folic acid fortification 44 and folic acid fortification in Mexico is not well enforced, 45 suggesting that suboptimal maternal folate status may have contributed to the changes observed in placental folate transport in those studies.…”

Section: Discussioncontrasting

confidence: 99%

“…Because folate deficiency is a well-established risk factor for NTDs [1][2][3] and may contribute to poor fetal growth, 5 20 and upregulated PCFT expression in placentae from fetuses with congenital anomalies (including, but not limited to, NTDs). 43 India does not have mandatory folic acid fortification 44 and folic acid fortification in Mexico is not well enforced, 45 suggesting that suboptimal maternal folate status may have contributed to the changes observed in placental folate transport in those studies.…”

Section: Discussionmentioning

confidence: 99%

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Altered placental immune cell composition and gene expression with isolated fetal spina bifida

White,

Abdo,

Grynspan

et al. 2024

American J Rep Immunol

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ProblemFetal spina bifida (SB) is more common in pregnant people with folate deficiency or anomalies of folate metabolism. It is also known that fetuses with SB have a higher risk of low birthweight, a condition that is typically placental‐mediated. We therefore hypothesized that fetal SB would associate with altered expression of key placental folate transporters and an increase in Hofbauer cells (HBCs), which are folate‐dependent placental macrophages.Method of studyFolate receptor‐α (FRα), proton coupled folate receptor (PCFT), and reduced folate carrier (RFC) protein localization and expression (immunohistochemistry) and HBC phenotypes (HBC abundance and folate receptor‐β [FRβ] expression; RNA in situ hybridization) were assessed in placentae from fetuses with SB (cases; n = 12) and in term (n = 10) and gestational age (GA) – and maternal body mass index – matched (n = 12) controls without congenital anomalies.ResultsCases had a higher proportion of placental villous cells that were HBCs (6.9% vs. 2.4%, p = .0001) and higher average HBC FRβ expression (3.2 mRNA molecules per HBC vs. 2.3, p = .03) than GA‐matched controls. HBCs in cases were largely polarized to a regulatory phenotype (median 92.1% of HBCs). In sex‐stratified analyses, only male cases had higher HBC levels and HBC FRβ expression than GA‐matched controls. There were no differences between groups in the total percent of syncytium and stromal cells that were positive for FRα, PCFT, or RFC protein immunolabeling.ConclusionsHBC abundance and FRβ expression by HBCs are increased in placentae of fetuses with SB, suggesting immune‐mediated dysregulation in placental phenotype, and could contribute to SB‐associated comorbidities.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Altered placental immune cell composition and gene expression with isolated fetal spina bifida

White,

Abdo,

Grynspan

et al. 2024

American J Rep Immunol

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show abstract

“…Contrary to our hypothesis, we found no differences in semi-quantitative assessments of placental folate transporter protein localisation or expression (for FRα, PCFT, and RFC) across study groups, and no associations between placental folate transporter expression and birthweight. Our findings are inconsistent with previous studies from India and Mexico, which have reported upregulated FRα and RFC expression in placentae from fetuses with NTDs 21 , and upregulated PCFT expression in placentae from fetuses with congenital anomalies (including, but not limited to, NTDs) 45 . India does not have mandatory folic acid fortification 46 and folic acid fortification in Mexico is not well enforced 47 , suggesting that suboptimal maternal folate status may have contributed to the changes observed in placental folate transport in these studies.…”

Section: Discussioncontrasting

confidence: 99%

Altered placental immune cell composition and gene expression with isolated fetal spina bifida

White,

Abdo,

Grynspan

et al. 2023

Preprint

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ProblemMaternal B vitamin deficiency increases the risk of fetal spina bifida (SB) and placental maldevelopment. It is unclear whether placental processes involving folate are altered in fetuses with SB in a contemporary cohort. We hypothesised that fetal SB would associate with reduced expression of key folate transporters (folate receptor-α [FRα], proton coupled folate receptor [PCFT], and reduced folate carrier [RFC]), and an increase in Hofbauer cell (HBC) abundance and folate receptor-β(FRβ)expression by HBCs.Method of StudyFRα, PCFT, and RFC protein localisation and expression (immunohistochemistry) and HBC phenotypes (RNAin situhybridization) were assessed in placentae from fetuses with SB (cases; n=12) and with no congenital anomalies (controls; n=22).ResultsCases (vs. gestational age [GA]-matched controls) had a higher proportion of placental villous cells that were HBCs (6.9% vs. 2.4%, p=0.0001) and higher averageFRβexpression by HBCs (3.2 mRNA molecules per HBC vs. 2.3, p=0.03). HBCs in cases were largely polarised to a regulatory (M2) phenotype (median 92.1% of HBCs). In sex-stratified analyses, male, but not female, cases had higher HBC levels andFRβexpression by HBCs than GA-matched controls. There were no differences between groups in the total percent of syncytium and stromal cells that were positive for FRα, PCFT, or RFC protein immunolabelling.ConclusionsHBC abundance andFRβexpression by HBCs are increased in placentae of fetuses with isolated SB, suggesting immune-mediated dysregulation in placental development and function, and could contribute to SB-associated comorbidities, such as poor fetal growth.

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“…Contrary to our hypothesis, we found no differences in semi-quantitative assessments of placental folate transporter protein localisation or expression (for FRα, PCFT, and RFC) across study groups, and no associations between placental folate transporter expression and birthweight. Our findings are inconsistent with previous studies from India and Mexico, which have reported upregulated FRα and RFC expression in placentae from fetuses with NTDs 315 , and upregulated PCFT expression in placentae from fetuses with congenital anomalies (including, but not limited to, NTDs) 330 . While data on maternal folate status were not available in either study, India does not have mandatory folic acid fortification 331 and folic acid fortification in Mexico is not well enforced 332 , suggesting that suboptimal maternal folate status may have contributed to the changes observed in placental folate transport in these studies.…”

Section: Discussioncontrasting

confidence: 99%

Early life programming of neurodevelopment and growth: understanding nutritional, inflammatory, and placental contributions in complex pregnancies

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Last, but certainly not least, I would like to thank my steadfast partner, Greg, for being a constant source of laughter, lightness, and love over the past four years. Greg has been a patient sounding board for many presentations, seminars, and my ever-evolving goals, and has been the antidote to my seriousness when things felt heavy. Having met only days before I began graduate school, I am so grateful to have had him alongside me for the entire journey. This experience would not have been the same without you.

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Folate transporter expression in placenta from pregnancies complicated with birth defects

Abstract: The expression of PCFT in placentas from BD-complicated pregnancies is increased, possibly as an adaptive response to increase the folate flux at the maternal-fetal interface.

Cited by 9 publications

References 20 publications

Altered placental immune cell composition and gene expression with isolated fetal spina bifida

Altered placental immune cell composition and gene expression with isolated fetal spina bifida

Altered placental immune cell composition and gene expression with isolated fetal spina bifida

Early life programming of neurodevelopment and growth: understanding nutritional, inflammatory, and placental contributions in complex pregnancies

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