Folic acid uptake by the human syncytiotrophoblast: Interference by pharmacotherapy, drugs of abuse and pathological conditions

Keating, Elisa; Gonçalves, Pedro; Campos, Isabel; Costa, Fabíola; Martel, Fátima

doi:10.1016/j.reprotox.2009.07.001

Cited by 39 publications

(37 citation statements)

References 63 publications

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“…These actions have been hypothesized to contribute to preterm labor associated with AMPH exposure (Cordeaux et al, 2008). To date, fetal AMPH exposure has not been proven to be directly teratogenic; however, in primary human cell cultures, AMPH reduced folic acid uptake and this could potentially lead to placental and/or fetal toxicity (Keating et al, 2009). Animal studies revealed at a prepubertal age, an enhancement of D1 receptors in the dorsal striatum and nucleus accumbens (NAc) and a decrement of the D3 receptors in NAc, olfactory tubercle, and the islands of Calleja.…”

Section: Amphetaminementioning

confidence: 99%

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Ross

Graham

Money

et al. 2014

Neuropsychopharmacol

328

241

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Most drugs of abuse easily cross the placenta and can affect fetal brain development. In utero exposures to drugs thus can have long-lasting implications for brain structure and function. These effects on the developing nervous system, before homeostatic regulatory mechanisms are properly calibrated, often differ from their effects on mature systems. In this review, we describe current knowledge on how alcohol, nicotine, cocaine, amphetamine, Ecstasy, and opiates (among other drugs) produce alterations in neurodevelopmental trajectory. We focus both on animal models and available clinical and imaging data from cross-sectional and longitudinal human studies. Early studies of fetal exposures focused on classic teratological methods that are insufficient for revealing more subtle effects that are nevertheless very behaviorally relevant. Modern mechanistic approaches have informed us greatly as to how to potentially ameliorate the induced deficits in brain formation and function, but conclude that better delineation of sensitive periods, dose-response relationships, and long-term longitudinal studies assessing future risk of offspring to exhibit learning disabilities, mental health disorders, and limited neural adaptations are crucial to limit the societal impact of these exposures.

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Section: Amphetaminementioning

confidence: 99%

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Ross

Graham

Money

et al. 2014

Neuropsychopharmacol

328

241

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“…Accordingly, our group had previously demonstrated that 3 H-FA uptake by NTB cells was insensitive to short-term hyperglycemia and to both shortand long-term insulin exposure (32).…”

Section: Discussionmentioning

confidence: 98%

“…The transport experiments in NTB, DTB, and BeWo cells were performed in buffer with the following composition (in mmol/l): 125 NaCl, 4.8 KCl, 1.2 KH 2 PO 4 , 12.5 HEPES-NaOH, 12.5 2-[N-morpholino]ethanesulfonic acid hydrate (Sigma), 1.2 MgSO 4 , 1.2 CaCl 2 , and 5.6 mmol/l D(+)-glucose (Merck, Darmstadt, Germany), pH 5.5 or 7.5 (unless otherwise stated), as previously described (32). 3 H-FA was used in concentrations of 20 or 50 nmol/l (except in the experiments for determination of the kinetics of 3 H-FA uptake).…”

Section: Fa Uptake Studiesmentioning

confidence: 99%

“…The concentrations of folate analogs of SITS and of TPP used in the characterization of FA uptake were chosen based on previous work from our group (30,32,43) and others (7,35,44).…”

Section: Fa Uptake Studiesmentioning

confidence: 99%

“…Cells were exposed to different concentrations of d-glucose, insulin, leptin, LPS or TNF-α, or the respective solvent in fetal calf serum-free culture medium for 1, 4, or 24 h. After these treatments, transport experiments were performed as previously described (32). The effect of inhibitors of signaling pathways was tested by cultivating cells, during specific time periods, in fetal calf serum-free medium containing selected GDM markers (which significantly altered 3 H-FA uptake) plus these inhibitors or the respective solvents.…”

Section: Effect Of Gdm-associated Hallmarks On 3 H-fa Uptake In Bewo mentioning

confidence: 99%

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Folic acid uptake by the human syncytiotrophoblast is affected by gestational diabetes, hyperleptinemia, and TNF-α

et al. 2013

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Background:The mechanisms whereby gestational diabetes mellitus (GDM) increases the risk of fetal overgrowth and development of metabolic diseases later in life are likely to involve changes in nutrient supply to the fetus. hence, in this work, we hypothesize that GDM may affect folic acid (Fa) supply to the placenta and fetus. Methods: We compared 3 h-Fa uptake by human cytotrophoblasts isolated from normal pregnancies (normal trophoblasts; NTB cells) and GDM pregnancies (diabetic trophoblasts; DTB cells) and investigated the effect of GDM hallmarks on 3 h-Fa uptake by BeWo cells. results: 3 h-Fa uptake by NTB and DTB cells was time dependent and acidic ph stimulated. When compared with NTB, 3 h-Fa uptake by DTB cells was more sensitive to acidic ph changes and to 5-methyltetrahydrofolate and pemetrexed (PTX) inhibition, indicating a proportionally greater involvement of the proton-coupled folate transporter (PcFT). a 4-h exposure of BeWo cells to lipopolysaccharide (LPs, 1-10 μg/ml) or to high levels of tumor necrosis factor-α (TNF-α, 300 ng/l) significantly reduced 3 h-Fa uptake. Moreover, hyperleptinemic conditions (100 ng/ml leptin) decreased 3 h-Fa uptake by BeWo cells in a time-dependent manner when compared with normoleptinemic conditions (1 ng/ml leptin). conclusion: GDM modulates 3 h-Fa uptake by the syncytiotrophoblast, and leptin as well as TNF-α downregulate it.

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The role of teratogens in neural crest development

Cerrizuela

Vega-Lopez

Aybar

2020

Birth Defects Research

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The neural crest (NC), discovered by Wilhelm His 150 years ago, gives rise to a multipotent migratory embryonic cell population that generates a remarkably diverse and important array of cell types during the development of the vertebrate embryo. These cells originate in the neural plate border (NPB), which is the ectoderm between the neural plate and the epidermis. They give rise to the neurons and glia of the peripheral nervous system, melanocytes, chondrocytes, smooth muscle cells, odontoblasts and neuroendocrine cells, among others. Neurocristopathies are a class of congenital diseases resulting from the abnormal induction, specification, migration, differentiation or death of NC cells (NCCs) during embryonic development and have an important medical and societal impact. In general, congenital defects affect an appreciable percentage of newborns worldwide. Some of these defects are caused by teratogens, which are agents that negatively impact the formation of tissues and organs during development. In this review, we will discuss the teratogens linked to the development of many birth defects, with a strong focus on those that specifically affect the development of the NC, thereby producing neurocristopathies.Although increasing attention is being paid to the effect of teratogens on embryonic development in general, there is a strong need to critically evaluate the specific role of these agents in NC development. Therefore, increased understanding of the role of these factors in NC development will contribute to the planning of strategies aimed at the prevention and treatment of human neurocristopathies, whose etiology was previously not considered.

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Folic acid uptake by the human syncytiotrophoblast: Interference by pharmacotherapy, drugs of abuse and pathological conditions

Cited by 39 publications

References 63 publications

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Developmental Consequences of Fetal Exposure to Drugs: What We Know and What We Still Must Learn

Folic acid uptake by the human syncytiotrophoblast is affected by gestational diabetes, hyperleptinemia, and TNF-α

The role of teratogens in neural crest development

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