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Neurologic disorders in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Robert Burger, Terry Rolan, David Lardizabal, Upinder Dhand, Aarti Sarwal, Pradeep Sahota
The mechanism underlying adverse AED effects on development is uncertain. Teratogens interact with genotype to produce both anatomic and behavioral defects (59). Whether a defect occurs depends on susceptible genotype and may involve interaction of multiple liability genes. Proposed mechanisms underlying teratogenicity of AEDs include folate, ischemia, neuronal suppression, reactive intermediates (e.g., epoxides or free radicals), and AED-induced neuronal apoptosis. Neuronal dysfunction short of apoptosis or migration disorders may also contribute. Mechanisms of anatomic and behavioral teratogenesis may well differ since it appears that anatomic defects result from first-trimester AED exposure while behavioral defects arise from third-trimester exposure. A leading hypothesis of anatomic teratogenesis involves oxidative macromolecular damage from free radicals formed as reactive intermediates of AED metabolism. AED-induced apoptosis has been proposed as a possible mechanism for the behavioral deficits. Widespread neuronal apoptosis in animals occurs as a result of exposure to clonazepam, diazepam, PB, PHT, VG, or valproate in neonatal rats. The effect is dose dependent, occurs at therapeutically relevant blood levels, requires only a relatively brief exposure, and can be synergistic suggesting possible increased polytherapy risk. Similar apoptotic effects were not seen at therapeutic dosages for CBZ, LEV, lamotrigine, or TPM monotherapy. Further, fetal exposure of GABAergic AEDs such as valproate and VG can result in hippocampal and cortical dysplasia secondary to impaired migration and neuronal death.
Gastrointestinal disease
Published in Catherine Nelson-Piercy, Handbook of Obstetric Medicine, 2020
Extensive data exist to show a lack of teratogenesis or other adverse pregnancy outcomes with Antihistamines (H1-receptor antagonists e.g. promethazine, cyclizine, cinnarizine, doxylamine, dimenhydrinate)Phenothiazines (chlorpromazine, prochlorperazine)Dopamine antagonists (metoclopramide, domperidone)Serotonin (5HT3) inhibitors (ondansetron)
The Chemical Environment
Published in Vilma R. Hunt, Kathleen Lucas-Wallace, Jeanne M. Manson, Work and the Health of Women, 2020
Vilma R. Hunt, Kathleen Lucas-Wallace, Jeanne M. Manson
The unique observation (so far) of human transplacental carcinogenesis due to die-thylstilbesterol (DES) is not surprising, in view of the likely necessity for enzyme-mediated metabolic conversion of most carcinogens to a chemically reactive derivative.126 Fetal tissue usually lacks the drug-metabolizing enzymes necessary for such conversions. There is an extensive literature on transplacental carcinogenesis in animals, which has been summarized by Rice, in addition to that on experimental neonatal carcinogenesis. Published case studies in which childhood cancer is related to in utero exposure to a toxic substance have so far been inadequate to sustain a hypothesis of causal relationship.127 The more likely effect of excessive exposure to a toxic chemical is teratogenesis, embryonic loss, or fetal-growth retardation. However, the conservative view is to keep in mind the DES experience, and to minimize any likelihood that maternal exposure to carcinogens might occur.
Role of DNA damage and repair in radiation cancer therapy: a current update and a look to the future
Published in International Journal of Radiation Biology, 2020
Jingya Liu, Kun Bi, Run Yang, Hongxia Li, Zacharenia Nikitaki, Li Chang
DNA damage and cellular response to it is a key factor for another RT related concern; that is female fertility and oocytes quality upon RT/medical or accidental exposures to IR. The central dogma till about -a decade ago- was that all (primary) oocytes are present to the female body since birth and that they do not have any DNA repair machinery. This would double the risk of the fetus developing into teratogenesis. Tilly et al was among the first groups who support that adult females replenish their primordial germ cell pool, likewise males (Tilly et al. 2009). Moreover, DNA repair machinery of oocytes has now been proved that does exist, although its efficiency remains an open issue, as well as, to which extent is similar to somatic cells’ DNA repair (Winship et al. 2018). Regardless oocytes DNA repair efficiency, the chance of misrepair is always present, causing “hereditable” mutations to the upcoming fetus. The extent of reproductive problems upon RT for pelvic, cervical or rectal cancer depends on irradiation regime features, as well as on patients’ age. RT treated pre-pubertal girls are expected to face infertility in adulthood (Adriaens et al. 2009). The underlying mechanisms of ovarian follicle radiosensitivity are still unclear, but we expect to be associated to DNA repair.
Genotoxic and mutagenic studies of teratogens in developing rat and mouse
Published in Drug and Chemical Toxicology, 2019
Eyyüp Rencüzoğulları, Muhsin Aydın
Teratogens are defined as agents that cause congenital defects. The effects of these agents depend on the time of exposure of the pregnant women, the dose of the medicine, the duration of the drug exposure, and the genetic susceptibility of the person. In Environment and Birth Defects book, which was published by James G. Wilson in 1973, it was stated that chemicals kill the embryo when taken in the early embryonic period and causes structural abnormalities in the embryogenesis period (Wilson, 1973). In the same book, Wilson stated that all mutagens could not be teratogenic, but the mechanisms of teratogenesis was listed as follows: (a) mutation, (b) chromosomal breaks or nondisjunction, (c) miotic interference, (d) altered nucleic acid integrity or function, (e) lack of precursors, (f) altered energy sources, (g) enzyme inhibition, (h) fluid-osmolyte imbalance, and (i) changed membrane characteristics. This suggests that genotoxic and mutagenic agents may also be teratogenic (el-Ashmawy et al. 2011, Shreder et al. 2011, Murkunde et al. 2012, El-Shershaby et al. 2014, Carvalho et al. 2016). Similarly, Wedebye et al. (2015) reported that the germline mutations were reproductive toxic.
Nanoparticles as a potential teratogen: a lesson learnt from fruit fly
Published in Nanotoxicology, 2019
Bedanta Kumar Barik, Monalisa Mishra
Various studies of NPs using Drosophila suggest that NP causes detrimental effect on development at cellular, molecular, genetic, and behavioral level. Exposure of NP at embryonic level alters the developmental process and brings out an alteration in adult for a successive generation without causing any lethality (Posgai et al. 2011; Vecchio et al. 2012; Anand et al. 2017). Can we include NP as a teratogen? The result of NPs from various studies suggests that NPs act as a teratogen. If we look at the explanation of teratogens, then these are any external factors (chemical, physical), which hamper the developmental process if ingested during the prenatal development period and the effects are sustained throughout the life of the organism (Coyle et al. 1976). Anomalies caused by teratogens can be anatomical, morphological, physiological or behavioral (Coyle et al. 1976) which are combined effect of molecular, cellular, and biochemical alterations (Wilson 1968). The process of alteration of the developmental cycle and bringing about modifications is known as teratogenesis. In this review, we are summarizing all the studies which use D. melanogaster as a model organism where NPs act as a potential teratogen.