Birth Defects Research Part C-Embryo Today-Reviews最新文献

Worldwide epidemiological studies have shown that exposures to particulate matters (PMs), such as PM_2.5 or PM₁₀, during pregnancy cause birth defects in the newborn. Although mechanistic understanding of such effects are not available, recent research using murine models highlights some key progress: (1) toxicity caused by PMs is a combined effects of particles and the adsorbed toxic pollutants, such as heavy metals, persistent organic pollutants, bacteria, and virus. Fine particles may hold on to pollutants and, therefore, reduce their toxicity or enhance the toxicity by carrying pollutants crossing the placental barrier; (2) smaller size, certain particle surface chemistry modifications, early developmental stage of placenta, and maternal diseases all aggravate PM-induced birth defects; (3) molecular events involved in such toxicity are begin to emerge: induction of oxidative stress, DNA damage, and alteration of molecular signaling or epigenetic events are some possible causes. Despite this progress, a clear understanding of PM-induced birth defects awaits further breakthroughs on many fronts, including epidemiological studies, animal models, nanotoxicity, and molecular mechanism investigations. Birth Defects Research (Part C) 108:196–206, 2016. © 2016 Wiley Periodicals, Inc.

Prenatal substance use remains a significant issue in the United States. Initial reports regarding prenatal cocaine and methamphetamine exposure suggested profound adverse effects on child development. However, subsequent prospective, longitudinal investigations have found more subtle effects. What follows is a brief review of the health, growth, behavioral, and intellectual outcomes for children exposed to prenatal cocaine and prenatal methamphetamine. Factors that may mitigate or intensify subtle adverse effects manifested in exposed children will also be discussed. Birth Defects Research (Part C) 108:142–146, 2016. © 2016 Wiley Periodicals, Inc.

In utero exposure of mouse progeny to alcohol (ethanol, EtOH) and methamphetamine (METH) causes substantial postnatal neurodevelopmental deficits. One emerging pathogenic mechanism underlying these deficits involves fetal brain production of reactive oxygen species (ROS) that alter signal transduction, and/or oxidatively damage cellular macromolecules like lipids, proteins, and DNA, the latter leading to altered gene expression, likely via non-mutagenic mechanisms. Even physiological levels of fetal ROS production can be pathogenic in biochemically predisposed progeny, and ROS formation can be enhanced by drugs like EtOH and METH, via activation/induction of ROS-producing NADPH oxidases (NOX), drug bioactivation to free radical intermediates by prostaglandin H synthases (PHS), and other mechanisms. Antioxidative enzymes, like catalase in the fetal brain, while low, provide critical protection. Oxidatively damaged DNA is normally rapidly repaired, and fetal deficiencies in several DNA repair proteins, including oxoguanine glycosylase 1 (OGG1) and breast cancer protein 1 (BRCA1), enhance the risk of drug-initiated postnatal neurodevelopmental deficits, and in some cases deficits in untreated progeny, the latter of which may be relevant to conditions like autism spectrum disorders (ASD). Risk is further regulated by fetal nuclear factor erythroid 2-related factor 2 (Nrf2), a ROS-sensing protein that upregulates an array of proteins, including antioxidative enzymes and DNA repair proteins. Imbalances between conceptal pathways for ROS formation, versus those for ROS detoxification and DNA repair, are important determinants of risk. Birth Defects Research (Part C) 108:108–130, 2016. © 2016 Wiley Periodicals, Inc.

Exposure to drugs early in life has complex and long-lasting implications for brain structure and function. This review summarizes work to date on the immediate and long-term effects of prenatal exposure to cocaine. In utero cocaine exposure produces disruptions in brain monoamines, particularly dopamine, during sensitive periods of brain development, and leads to permanent changes in specific brain circuits, molecules, and behavior. Here, we integrate clinical studies and significance with mechanistic preclinical studies, to define our current knowledge base and identify gaps for future investigation. Birth Defects Research (Part C) 108:147–173, 2016. © 2016 Wiley Periodicals, Inc.

Maternal smoking during pregnancy continues to represent a major public health concern. Nicotine is extremely harmful to the developing fetus through many different mechanisms, and the harms increase with later gestational age at exposure. Pregnancies complicated by maternal nicotine use are more likely to have significant adverse outcomes. Nicotine-exposed children tend to have several health problems throughout their lives, including impaired function of the endocrine, reproductive, respiratory, cardiovascular, and neurologic systems. Poor academic performance and significant behavioral disruptions are also common, including ADHD, aggressive behaviors, and future substance abuse. To diminish the adverse effects from cigarette smoking, some women are turning to electronic cigarettes, a new trend that is increasing in popularity worldwide. They are largely perceived as being safer to use in pregnancy than traditional cigarettes, although there is not adequate evidence to support this claim. At this time, electronic cigarette use during pregnancy cannot be recommended. Birth Defects Research (Part C) 108:181–192, 2016. © 2016 Wiley Periodicals, Inc.

Methamphetamine exposure in utero leads to a variety of higher-order cognitive deficits, such as decreased attention and working, and spatial memory impairments in exposed children (Piper et al., 2011; Roussotte et al., 2011; Kiblawi et al., 2011). As with other teratogens, the timing of methamphetamine exposure greatly determines its effects on both neuroanatomical and behavioral outcomes. Methamphetamine exposure in rodents during the third trimester human equivalent period of brain development results in distinct and long-lasting route-based and spatial navigation deficits (Williams et al., 2003; Vorhees et al., 2005, 2008, 2009;). Here, we examine the impact of neonatal methamphetamine-induced neurotoxicity on behavioral outcomes, neurotransmission, receptor changes, plasticity proteins, and DNA damage. Birth Defects Research (Part C) 108:131–141, 2016. © 2016 Wiley Periodicals, Inc.