Developing a link between toxicants, claudins and neural tube defects

Gamero-Estevez, Enrique; Baumholtz, Amanda I.; Ryan, Aimee K.

doi:10.1016/j.reprotox.2018.08.008

Cited by 9 publications

(10 citation statements)

References 193 publications

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“…The bending of the neural plate depends on the formation of the midline hinge and the dorsal lateral hinge area, which is the key to the formation of neural tubes (Greene & Copp, 2014; Nikolopoulou et al, 2017). If the process is affected by teratogen, neural tube defects may occur (Gamero‐Estevez et al, 2018). In our experiment, passive smoking was given from the first trimester.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies in humans or animals have shown that cigarette smoke can change the expression of tight junction proteins and change the stability of the placental barrier (Gamero‐Estevez, Baumholtz, & Ryan, 2018). Even in early pregnancy, cigarette smoke components can pass through the placenta and can be detected in newborns' urine (Granfors et al, 2019; Heidari, Mahmoudzadeh‐Sagheb, & Sheibak, 2018).…”

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confidence: 99%

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Cigarette smoke induced neural tube defects by down‐regulating noggin expression

Yin

Cai

Yang

et al. 2020

Birth Defects Research

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Background Maternal smoking or passive smoking during gestation increases the risk of congenital birth defects, including neural tube defects (NTDs). Cigarette smoke is a recognized teratogen that causes NTDs, although the mechanisms are not well understood. Methods An established model of passive smoking in pregnant golden hamsters was used to observe the effect of cigarette smoke on neural tube development using scanning electron microscopy. Level of noggin expression in placenta and neural tube was evaluated by immunohistochemistry. Results Our results indicated that cigarette smoke can cause the neural tube closure of the golden hamster embryo to be delayed or not closed. In normal placental tissues noggin protein and RNA levels were highly expressed, and the expression level in the term placenta was lower than in that of the first trimester or second trimester through analyzing the Human Protein Atlas and the Gene Expression Omnibus (GEO) databases. Cigarette smoke can down‐regulate noggin expression in the placenta and promote cell apoptosis. We observed that noggin expression was reduced and BMP2 expression was increased by cigarette smoke. Conclusions Cigarette smoke may cause cell apoptosis and accelerate placenta maturation. Meanwhile, cigarette smoke may inhibit the development of the embryo, and lead to the formation of NTDs via downregulating the expression of noggin and dis‐inhibition of BMP2.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cigarette smoke induced neural tube defects by down‐regulating noggin expression

Yin

Cai

Yang

et al. 2020

Birth Defects Research

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“…NT closure involves converting a flat epithelium, that is, ectoderm into a closed elongated tube followed by formation of forebrain, midbrain, and hindbrain (Aristizabal et al, 2013). Cytokines and growth factors are essential for the dynamic process of cell growth and proliferation during embryonic development, characterized by morphological changes at the level of individual cells that are translated into large-scale changes such as successful NT closure (Gamero-Estevez, Baumholtz, & Ryan, 2018). VPA can accumulate and is retained in the cells of neuroepithelium resulting in failure of anterior neuropore closure (Dencker, Nau, & D'argy, 1990;Nau, 1985).…”

Section: Discussionmentioning

confidence: 99%

Gestational exposure to valproic acid upregulates total Stat3 protein expression while downregulating phosphorylated Stat3 in CD‐1 mouse embryos with neural tube defects

Shafique

Winn

2020

Birth Defects Research

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Valproic acid (VPA), a widely prescribed antiepileptic drug and an effective treatment for psychiatric disorders, is teratogenic causing neural tube defects (NTDs) and other defects in the exposed embryo. Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is activated via tyrosine phosphorylation. Stat3, as well as its active form (pYStat3), is expressed during neural tube closure in murine development. This study investigated the effects of in utero VPA exposure on embryonic Stat3 mRNA and protein expression during the critical period of neural tube closure in CD‐1 mouse embryos. Following the exposure of CD‐1 pregnant mice to the teratogenic dose of 400 mg/kg VPA or saline on gestational day (GD) 9, embryos were harvested at 1, 3, 6, or 24 hr and on GD13. Stat3 mRNA levels remained unchanged at all time points. Total Stat3 protein levels were significantly (p < .05) increased in GD9 embryos at 1 and 6 hr post‐exposure and in GD13 exposed nonexencephalic and exencephalic embryo heads. In contrast, phosphorylated Stat3 levels were significantly (p < .05) downregulated in GD9 embryos at the 3 and 6 hr time points with an overall trend of downregulation in the GD10 and GD13 groups. Total and phosphorylated Stat3 protein levels remained unchanged in nuclear extracts of the exposed nonexencephalic and exencephalic GD13 embryo heads. The reported significant downregulation of phosphorylated Stat3 levels suggests its possible role in VPA‐induced NTDs in mouse embryos.

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“…Quercetin is known to bind to several membrane-bound nutraceutical receptors that signal through different pathways to reduce oxidative stress. Quercetin also interacts directly with several kinases [48,49,50,51,52]. Some studies show that it is a potent inhibitor of PI3K/AKT pathway [36,53]; although there is some controversy [49,54,55], while others show that it inhibits the ERK and NF-κβ pathways [56], and activates the AMPK pathway [49,57].…”

Section: Discussionmentioning

confidence: 99%

Temporal Effects of Quercetin on Tight Junction Barrier Properties and Claudin Expression and Localization in MDCK II Cells

Gamero-Estevez

Andonian

Jean‐Claude

et al. 2019

IJMS

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Kidney stones affect 10% of the population. Yet, there is relatively little known about how they form or how to prevent and treat them. The claudin family of tight junction proteins has been linked to the formation of kidney stones. The flavonoid quercetin has been shown to prevent kidney stone formation and to modify claudin expression in different models. Here we investigate the effect of quercetin on claudin expression and localization in MDCK II cells, a cation-selective cell line, derived from the proximal tubule. For this study, we focused our analyses on claudin family members that confer different tight junction properties: barrier-sealing (Cldn1, -3, and -7), cation-selective (Cldn2) or anion-selective (Cldn4). Our data revealed that quercetin’s effects on the expression and localization of different claudins over time corresponded with changes in transepithelial resistance, which was measured continuously throughout the treatment. In addition, these effects appear to be independent of PI3K/AKT signaling, one of the pathways that is known to act downstream of quercetin. In conclusion, our data suggest that quercetin’s effects on claudins result in a tighter epithelial barrier, which may reduce the reabsorption of sodium, calcium and water, thereby preventing the formation of a kidney stone.

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Developing a link between toxicants, claudins and neural tube defects

Cited by 9 publications

References 193 publications

Cigarette smoke induced neural tube defects by down‐regulating noggin expression

Cigarette smoke induced neural tube defects by down‐regulating noggin expression

Gestational exposure to valproic acid upregulates total Stat3 protein expression while downregulating phosphorylated Stat3 in CD‐1 mouse embryos with neural tube defects

Temporal Effects of Quercetin on Tight Junction Barrier Properties and Claudin Expression and Localization in MDCK II Cells

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