Reversal of neurobehavioral teratogenicity in animal models and human: Three decades of progress

Yanai, Joseph; Vigoda, Myles J.; Ornoy, Asher

doi:10.1016/j.brainresbull.2019.06.009

Cited by 6 publications

(3 citation statements)

References 175 publications

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“…A vivid example is the need to continue the treatment with anti-seizure medications in spite of their possible teratogenicity. Hence, the possibility to prevent the undesirable effects of a teratogen is of utmost importance [ 225 ]. A vivid example for such an approach is the prevention of NTD and other malformations by folic acid that has the backing of many animal and human studies.…”

Section: The Prevention Of Vpa Teratogenicity In Animals In Relation ...mentioning

confidence: 99%

Valproic Acid in Pregnancy Revisited: Neurobehavioral, Biochemical and Molecular Changes Affecting the Embryo and Fetus in Humans and in Animals: A Narrative Review

Ornoy,

Echefu,

Becker

2023

IJMS

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Valproic acid (VPA) is a very effective anticonvulsant and mood stabilizer with relatively few side effects. Being an epigenetic modulator, it undergoes clinical trials for the treatment of advanced prostatic and breast cancer. However, in pregnancy, it seems to be the most teratogenic antiepileptic drug. Among the proven effects are congenital malformations in about 10%. The more common congenital malformations are neural tube defects, cardiac anomalies, urogenital malformations including hypospadias, skeletal malformations and orofacial clefts. These effects are dose related; daily doses below 600 mg have a limited teratogenic potential. VPA, when added to other anti-seizure medications, increases the malformations rate. It induces malformations even when taken for indications other than epilepsy, adding to the data that epilepsy is not responsible for the teratogenic effects. VPA increases the rate of neurodevelopmental problems causing reduced cognitive abilities and language impairment. It also increases the prevalence of specific neurodevelopmental syndromes like autism (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). High doses of folic acid administered prior to and during pregnancy might alleviate some of the teratogenic effect of VPA and other AEDs. Several teratogenic mechanisms are proposed for VPA, but the most important mechanisms seem to be its effects on the metabolism of folate, SAMe and histones, thus affecting DNA methylation. VPA crosses the human placenta and was found at higher concentrations in fetal blood. Its concentrations in milk are low, therefore nursing is permitted. Animal studies generally recapitulate human data.

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Section: The Prevention Of Vpa Teratogenicity In Animals In Relation ...mentioning

confidence: 99%

Valproic Acid in Pregnancy Revisited: Neurobehavioral, Biochemical and Molecular Changes Affecting the Embryo and Fetus in Humans and in Animals: A Narrative Review

Ornoy,

Echefu,

Becker

2023

IJMS

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“…The behavioral and molecular deficits observed in the offspring after prenatal/pre-hatch exposure to insults such as chemicals, drugs and pesticides has been well documented 1 – 4 . Reversal of neurobehavioral defects after exposure to different teratogens was applicable after understanding the mechanisms mediating such effects 5 – 7 .…”

Section: Introductionmentioning

confidence: 99%

Whole transcriptome analysis in offspring whose fathers were exposed to a developmental insult: a novel avian model

Rimawi,

Yanai,

Turgeman

et al. 2023

Sci Rep

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Although the effects of paternal exposure to insults on the offspring received limited attention in the past, it is currently gaining interest especially after understanding the mechanisms which may mediate such exposure effects. In the current study, the well-controlled avian model (Fayoumi) was utilized to investigate the effects of paternal exposure to the developmental insult, chlorpyrifos on the offspring’s gene expression via mRNA and small RNA sequencing. Numerous mRNA gene expression changes were detected in the offspring after paternal exposure to the developmental insult, especially in genes related to neurogenesis, learning and memory. qPCR analysis of several genes, that were significantly changed in mRNA sequencing, confirmed the results obtained in mRNA sequencing. On the other hand, small RNA sequencing did not identify significant microRNA genes expression changes in the offspring after paternal exposure to the developmental insult. The effects of the paternal exposure were more pronounced in the female offspring compared to the male offspring. The results identified expression alterations in major genes (some of which were pertinent to the functional changes observed in other forms of early developmental exposure) after paternal insult exposure and provided a direction for future studies involving the most affected genes.

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“…De esta forma, la Teratología Conductual, es un híbrido entre la Psicología Experimental, que enfatiza en la conducta, y la Teratología (derivada de la embriología y anatomía), que se enfoca en los factores que alteran el desarrollo (Abel, 2012). Este campo pertenece a las neurociencias, puesto que analiza las perturbaciones funcionales del desarrollo del cerebro y las áreas afectadas (Abel, 2012), y reúne el trabajo de varias disciplinas, como de psicobiólogos, epidemiólogos, neurofisiólogos, neuroanatomistas, neuroquímicos, farmacólogos y otros científicos que integran sus esfuerzos para entender cómo y por qué algunas personas nunca alcanzan a desarrollar su total potencial (Abel, 2012;Riley & Vorhees, 2012;Yanai et al, 2019).…”

Section: Introductionunclassified

Teratología conductual: un apasionante campo de trabajo transdisciplinar

Ortega¹

2022

Investigación en Psicología: Aplicaciones E Intervenciones II

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Desde el impresionante precedente de la tragedia de la Talidomida, un ansiolítico, hipnótico y antiemético usado en el primer trimestre de la gestación que causó graves malformaciones cardíacas, renales, digestivas, oftálmicas auditivas y ausencia total o parcial de los miembros superiores/inferiores, entre otras, y a partir de trabajos como (DeSesso, 2019; Moore & Persaud, 2013; Papaseit et al., 2013), y la publicación del minucioso trabajo de Werboff & Gottlieb (1963) se estableció que las drogas de consumo materno durante la gestación –tanto las prescritas como las que no– tienen unos potentes efectos teratogénicos, es decir, producen malformaciones congénitas durante el desarrollo del infante. Estas malformaciones pueden darse en diferentes órganos o tejidos; y cuando ocurren en el sistema nervioso no son tan evidentes, y se reflejan en alteraciones del comportamiento que se pueden manifestar en la infancia, la adolescencia o más tardíamente. Cuando las malformaciones congénitas se observan en el comportamiento, pertenecen al campo de la Teratología Conductual o Teratología Neuroconductual (Minnes et al., 2014; Werboff & Gottlieb, 1963).

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Reversal of neurobehavioral teratogenicity in animal models and human: Three decades of progress

Cited by 6 publications

References 175 publications

Valproic Acid in Pregnancy Revisited: Neurobehavioral, Biochemical and Molecular Changes Affecting the Embryo and Fetus in Humans and in Animals: A Narrative Review

Valproic Acid in Pregnancy Revisited: Neurobehavioral, Biochemical and Molecular Changes Affecting the Embryo and Fetus in Humans and in Animals: A Narrative Review

Whole transcriptome analysis in offspring whose fathers were exposed to a developmental insult: a novel avian model

Teratología conductual: un apasionante campo de trabajo transdisciplinar

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