Placental Folate Transport during Pregnancy

Yasuda, Satoru; Hasui, Satoko; Yamamoto, Chiaki; Yoshioka, Chihiro; Kobayashi, Masaki; Itagaki, Shirou; Hirano, Takeshi; Iseki, Ken

doi:10.1271/bbb.80112

Cited by 53 publications

(50 citation statements)

References 38 publications

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“…Folate deficiency during pregnancy is associated with abnormalities in the fetus (Greenberg et al 2011;Safi et al 2012). The extent to which folic acid is transferred across the placenta and into the fetal circulation is mediated by placental folate transporters folate receptor-␣ at the microvillous membrane of the syncytiotrophoblast (Bisseling et al 2004;Solanky et al 2010), the reduced folate carrier, and the proton-coupled folate transporter (Prasad et al 1995;Yasuda et al 2008aYasuda et al , 2008b). Hutson and colleagues measured folate in both maternal blood and umbilical cord blood at the time of delivery in pregnancies with chronic and heavy alcohol exposure and in nondrinking controls.…”

Section: Folic Acid and Alcohol (Etoh)mentioning

confidence: 99%

FASD: folic acid and formic acid — an unholy alliance in the alcohol abusing mother

Kapur

Baber

2018

Biochem. Cell Biol.

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Alcohol consumption during pregnancy remains a significant cause of preventable birth defects and developmental disabilities; however, the mechanism of toxicity remains unclear. Methanol is present as a congener in many alcoholic beverages and is formed endogenously. Because ethanol is preferentially metabolized over methanol, it has been found in the sera and cerebro-spinal fluid of alcoholics. Toxicity resulting from methanol has been attributed to formic acid. Formic acid is present in significantly higher quantities in the biofluids of alcoholics. These higher levels can be cytotoxic and cause neuronal cell death. However, the adverse effects can be mitigated by adequate levels of hepatic folic acid, because formic acid elimination depends on folic acid. During pregnancy, folate concentrations are at least 2-fold higher in cord blood then in maternal blood, owing to increased folate requirements. The reverse has been demonstrated in pregnancies with alcohol abuse, suggesting downregulation of folate transporters and low fetal folate levels. Moreover, formic acid can cross the placenta and its adverse effects can be mitigated by folic acid. Thus, the combination of low fetal folate levels and presence of formic acid form a potent cytotoxic combination that may play a significant role in the etiology of fetal alcohol spectrum disorder.Key words: formic acid, methanol, folic acid, FASD, neurotoxicity.Résumé : La consommation d'alcool pendant la grossesse demeure une cause significative de déficiences congénitales et développementales évitables, mais le mécanisme responsable de sa toxicité est encore flou. Le méthanol est présent comme congénère dans plusieurs boissons alcooliques et il est formé de manière endogène. Puisque l'éthanol est préférentiellement métabolisé par rapport au méthanol, ce dernier a été trouvé dans le sérum et le liquide céphalorachidien des personnes alcooliques. La toxicité résultant du méthanol a été attribuée à l'acide formique. L'acide formique est présent en quantité significativement plus élevée dans les liquides biologiques des patients alcooliques. Ces niveaux plus élevés peuvent être cytotoxiques et causer la mort neuronale. Cependant, ces effets nocifs peuvent être atténués par des niveaux appropriés d'acide folique hépatique, car l'élimination d'acide formique dépend de l'acide folique. Durant la grossesse, les concentrations de folate sont au moins deux fois plus élevées dans le cordon ombilical que dans le sang maternel à cause des besoins accrus en folate. L'inverse a été démontré chez les femmes enceintes qui abusent d'alcool, suggérant une régulation à la baisse des transporteurs du folate et de faibles niveaux foetaux de folate. En outre, l'acide formique peut traverser le placenta et ses effets nocifs peuvent être atténués par l'acide folique. Ainsi, de faibles niveaux foetaux de folate et la présence d'acide formique forment une combinaison cytotoxique puissante qui peut jouer un rôle significatif dans l'étiologie de troubles du spectre de l'alcoolisation foet...

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Section: Folic Acid and Alcohol (Etoh)mentioning

confidence: 99%

FASD: folic acid and formic acid — an unholy alliance in the alcohol abusing mother

Kapur

Baber

2018

Biochem. Cell Biol.

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“…1% of all congenital defects [35]. Most xenobiotics can cross the inefficient placental barrier and enter the foetal circulation [4,17,19,30,33,40,42]. The group of COX inhibitors in question does not display clear embryotoxicity or teratogenicity.…”

Section: Developmental and Reproductive Toxicitymentioning

confidence: 99%

Organ and prenatal toxicity of nonsteroidal anti-inflammatory drugs

Dyndor

Dworzański

Pliszczynska-Steuden

et al. 2015

Current Issues in Pharmacy and Medical Sciences

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Non-selective cyclooxygenase (COX) inhibitors, commonly referred to as nonsteroidal anti-inflammatory drugs (NSAIDs), are among the most taken pharmaceuticals. In adults, they can have a series of side effects, including especially gastroenterotoxicity, hepatotoxicity, nephrotoxicity, chondrotoxicity, and neurotoxicity, and they can induce allergic reactions. Any exacerbation of symptoms depends on the chemical structure of the drug, its dosage and duration of exposure, individual sensitivity, comorbidities and the degree of inhibition of basic COX isoenzymes -the constitutive (COX-2) and induced (COX-1) expressions. However, data on prenatal toxicity are inconsistent. Classic nonselective COX inhibitors do not result in an increase in the risk of developing significant congenital defects; however, if used in the late-pregnancy period, they can have an adverse effect on the foetus, by inducing the premature closure of the ductus arteriosus and by producing a tocolytic effect. Individual reports also indicate the increased risk of developing heart and anterior abdominal wall defects, as well as hypospadias.

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“…The delivery of nutrients from mother to fetus only occurs through the placenta [20]. Three specific folate transport mechanisms operate in the human placenta, including folate receptor (FOLR) in its -α (FOLR1) and β (FOLR2) forms [21], the reduced folate carrier (RFC) and the proton-coupled folate transporter (PCFT/HCP1) [22–24].…”

Section: Introductionmentioning

confidence: 99%

Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels

et al. 2017

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Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of specific folate transporters: RFC, PCFT/HCP1 and FOLR1 in chorionic (fetal) and basal (maternal) plates of placentas of PT pregnancies (PT, 32–36 weeks, n = 51). Term placentas were used as controls (T, 37–41 weeks, n = 47). Folates and vitamin B12 levels were measured by electrochemiluminescence in umbilical cord blood of newborns. FOLR1 mRNA expression was lower and protein concentration higher in PT placentas (both plates) relative to the control group (p <0.05). In addition, gestational age was positively correlated with mRNA expression (Rho = 0.7), and negatively with protein concentration (Rho = -0.7 for chorionic and -0.43 for basal plate). PCFT/HCP1 mRNA was lower in PT placentas, without changes in protein levels. RFC did not differ in PT placentas compared to controls. PT newborns presented higher cord blood folate level (p = 0.049) along with lower vitamin B12 concentration compared to controls (p = 0.037).In conclusion, placental FOLR1 mRNA was positively associated with gestational age. Conversely, FOLR1 protein concentrations along with folate/vitamin B12 ratio in cord blood were negatively associated with gestational age. Placental FOLR1 is likely the main placental folate transporter to the fetus in newborns.

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Placental Folate Transport during Pregnancy

Cited by 53 publications

References 38 publications

FASD: folic acid and formic acid — an unholy alliance in the alcohol abusing mother

FASD: folic acid and formic acid — an unholy alliance in the alcohol abusing mother

Organ and prenatal toxicity of nonsteroidal anti-inflammatory drugs

Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels

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