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In this study, the toxic and teratogenic effects of three commercial drugs and their active ingredients on Xenopus laevis embryos before and after ozonation were evaluated using the Frog Embryos Teratogenesis Assay–Xenopus (FETAX). First, the median lethal concentration (LC50) and, if data were available, the median effective concentration, teratogenic index and minimum growth inhibitory concentration were determined for each drug substance without ozonation. Then, the active substance amounts of three selected nominal concentrations (LC50/2, LC50, and LC50×2) of each test substance before ozonation were measured by HPLC analysis and the toxicity of these substances was evaluated after 2, 3, 4, and 5 h of ozonation. In addition, degradation products that may occur during ozonation were evaluated by LC-MS analysis. The 96-h LC50s of Dolphin–diflunisal, Dichloron–diclofenac sodium, and Apranax–naproxen drug–active substance pairs were determined to be 22.3 and 11.1, 25.7 and 18.7, and 47.8 mg active substance/L and 45.3 mg/L, respectively. According to the FETAX test results, the Dolphin–diflunisal drug–active ingredient pair did not cause growth retardation in exposed embryos. Dichloron–diclofenac sodium and Apranax–naproxen drug–active ingredient pairs were both teratogenic and growth inhibitory. In the second stage of the study, in which the effectiveness of ozonation in eliminating the toxic effects of drugs is evaluated, it is seen that ozonation is partially successful in eliminating the toxic effects of Dolphin–diflunisal and Dichloron–diclofenac sodium pairs, but insufficient for eliminating the effects of the Apranax–naproxen pair. [ABSTRACT FROM AUTHOR]

Prenatal ethanol exposure can cause a broad range of abnormalities in newborns known as Fetal Alcohol Spectrum Disorder (FASD). Despite significant progress in understanding the disease mechanisms of FASD, there remains a strong global need for effective therapies. To evaluate the therapeutic potential of sulforaphane (SFN), an active compound extracted from cruciferous vegetables, in preventing FASD, ethanol-exposed zebrafish embryos were pretreated, co-treated, or post-treated with various concentrations of SFN. The FASD-like morphological features, survival rate, hatching rate, and vascular development were then assessed in the zebrafish embryos. It was found that pretreatment with 2 μM SFN during 3–24 hpf had no noticeable protective effects against teratogenicity induced by subsequent 1.5% ethanol exposure during 24–48 hpf. In contrast, co-treatment with 2 μM SFN and 1.5% ethanol during 3–24 hpf significantly alleviated a range of ethanol-induced malformations, including reduced body length, small eyes, reduced brain size, small otic vesicle, small jaw, and pericardial edema. Post-treatment with 3 μM SFN for 4 days following 1.5% ethanol exposure during 3–24 hpf also significantly reduced the characteristic features of FASD, decreasing the mortality rate and restoring body length, eye size, brain size, and otic vesicle circumference. Moreover, we found that ethanol, even at a low dose (0.5%), causes vascular development deficit in the zebrafish embryos, which were also largely rescued by SFN treatment. These data indicated that SFN has great potential to be used in the prevention and treatment of FASD. [ABSTRACT FROM AUTHOR]

In 2019, there was an environmental catastrophe in Brazil, when more than 5000 tons of unknown origin crude oil invaded beaches and mangroves. Two years later, two monitoring areas were selected to study seahorses' offspring: Massangana River estuary (apparently healthy area) and Cocaia Island (affected area). Thirty‐six reproductive events of Hippocampus reidi (Syngnathidae) couples from these two areas were monitored to analyze the offspring. At the apparently healthy area, no newborns with malformations were found. However, the offspring from Cocaia Island showed a mean of 19.73% (±5.23) malformations in newborns. It is argued that the toxic/teratogenic effects of polycyclic aromatic hydrocarbons have affected the population in two ways: directly through the induction of mutations in the germ cells of the species and through a drastic reduction of the population (bottleneck effect) whose density observed today recovered through consanguineous couplings, potentiating deleterious genotypes in the offspring. Environ Toxicol Chem 2024;43:1996–2004. © 2024 SETAC [ABSTRACT FROM AUTHOR]

Simple Summary: This report characterized complete thoracic ectopia cordis (EC) affecting two newborn lambs from different locations in Brazil, contributing to the knowledge about this rare condition in sheep. Two male newborn lambs presented exteriorized hearts without pericardial coverage, delineated in the thoracic cleft by a fibrous ring of the pericardium and adjacent skin. Clinical findings in the lambs, aside from the EC, were unremarkable. EC is an extremely rare congenital malformation in sheep, with limited cases documented globally. The pathogenesis and etiology remain uncertain, involving potential genetic and environmental factors. Cardiac congenital defects related to inheritance and teratogenesis have been reported in veterinary species and humans worldwide. Among these, ectopia cordis (EC), characterized by an externalized heart through a cleft, is extremely rare in sheep. This report presents the diagnostic features of two cases of complete thoracic EC in newborn lambs. Clinical findings in the lambs, aside from the EC, were unremarkable. Both animals exhibited exteriorized hearts without pericardial coverage, delineated in the thoracic cleft by a fibrous ring of the pericardium and adjacent skin. Histologically, the epicardium was thickened by fibrous tissue in both lambs, with one animal also showing marked edema, hemorrhage, and neutrophilic inflammatory infiltration. The prognosis of EC in the lambs of this study was poor, with fatal outcomes despite attempts at surgical correction. [ABSTRACT FROM AUTHOR]

There are currently about 15 million women of childbearing age worldwide who suffer from epilepsy. Overall, 0.3–0.4% of newborns are born to mothers with epilepsy, and almost half of these women experience recurrent seizures. The article discusses issues related to pregnancy planning, the prognostic impact of seizure frequency, type and course of epilepsy on pregnancy outcomes, and potential risks associated with this condition. Summarized data from the latest recommendations for correction of therapy and data on changes in the pharmacokinetics of antiepileptic drugs during pregnancy are presented. A classification of antiepileptic drugs according to their teratogenic potential and their effect on the development and behaviour of the child is presented. Various approaches to pregnancy management are discussed. In addition, scenarios for pregnancy management in poorly controlled epilepsy and status epilepticus are discussed as well as adjustment of therapy in the postpartum period and measures for the safe care of newborns.

• Additional statistically significant evidence is now available that zonisamide is a probable maternal dose-related teratogen. • Zonisamide's teratogenicity, like that of topiramate and possibly acetazolamide, may be a manifestation of a class effect shared by sulphonamide-derived carbonic anhydrase inhibitors that possess a degree of antiseizure activity. • There was no statistically significant evidence of teratogenicity in relation to 9 other little-used ASMs in Australia. To investigate the risk of teratogenesis occurring in relation to intrauterine exposure to infrequently used antiseizure medications in Australia. Analysis of data contained in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs. There was statistically significant evidence that zonisamide, but not any other of nine infrequently used antiseizure medications in Australia, was associated with a risk of teratogenesis related to the maternal dose of the drug taken in at least the earlier half of pregnancy. The teratogenesis associated with zonisamide, like that associated with topiramate and possibly acetazolamide, may be an expression of a class effect shared among sulphonamide-derived carbonic anhydrase inhibitors that possess anti-seizure activity. [ABSTRACT FROM AUTHOR]

Blutaparon portulacoides (A.St.-Hil.), also known as capotirguá, pirrixu, and bredo-de-praia, is a bactericidal and anti-inflammatory agent used in folk medicine to treat leukorrhea. The present study evaluated the effects of an ethanolic extract of B. portulacoides (EEBp) on the reproductive performance, embryo-fetal development, and chromosomal stability of mice of pregnant female mice treated during the gestational period with oral EEBp (500 or 1000 mg/kg) or vehicle (1% Tween 80). EEBp did not alter biometric parameters, placental index, placental efficiency, or other parameters related to reproductive performance, neither embryo-fetal development and DNA integrity, but 500 and 1000 mg/kg EEBp decreased fetal and placental weight, respectively. Although the frequency of external and skeletal malformations did not differ between these groups and the control group, EEBp increased the frequency of reduced ossification of the presphenoid and xiphoid, which can be considered variants of normality. These findings indicate that EEBp is a safe and cost-effective treatment for leukorrhea during pregnancy, although caution should be exercised in its use. [Display omitted] • Extract of B. portulacoides did not significantly interfere with the reproductive performance • Extract of B. portulacoides did not significantly interfere with the embryo-fetal development of female mice. • Ethanolic extract of B. portulacoides was not genotoxic. [ABSTRACT FROM AUTHOR]

Information for organismal patterning can come from a variety of sources. We investigate the possibility that instructive influences for normal embryonic development are provided not only at the level of cells within the embryo, but also via interactions between embryos. To explore this, we challenge groups of embryos with disruptors of normal development while varying group size. Here, we show that Xenopus laevis embryos are much more sensitive to a diverse set of chemical and molecular-biological perturbations when allowed to develop alone or in small groups, than in large groups. Keeping per-embryo exposure constant, we find that increasing the number of exposed embryos in a cohort increases the rate of survival while incidence of defects decreases. This inter-embryo assistance effect is mediated by short-range diffusible signals and involves the P2 ATP receptor. Our data and computational model emphasize that morphogenesis is a collective phenomenon not only at the level of cells, but also of whole bodies, and that cohort size is a crucial variable in studies of ecotoxicology, teratogenesis, and developmental plasticity. The collective activity of cells enables embryos to overcome various perturbations. Here, authors show that at the higher (population) level, embryos also communicate. This enables larger groups to resist chemical and molecular-genetic teratogens. [ABSTRACT FROM AUTHOR]

Ambrosia tenuifolia is a perennial herbaceous plant of the Asteraceae family, commonly used in Paraguay for multiple purposes as an abortive, antipyretic, digestive, and against headaches commonly in the form of an infusion of aerial parts. However, the lack of information on adverse effects raises questions about its safety and potential side effects. This study was undertaken to establish the potential health risks of A. tenuifolia for human health by evaluation of the aqueous and ethanolic extracts on Danio rerio embryos and to determine the potential toxicity or teratogenicity of the aqueous extract on human cells using human peripheral blood lymphocytes (PBL). For the test with D. rerio, observations were made 24 to 96 hours after fertilization. Coagulation, somite formation, heart rate, blood flow, pigmentation, edema formation, hatching, and spinal deviation were evaluated. As a result, the extract has lethal, sublethal, and teratogenic effects on the embryonic development of D. rerio, whose effects were dose-dependent. In the PBL, cells with and without bioactivation with the solution containing the S9 fraction were found to have genotoxic effects. This study provides the first report of toxicity and genotoxic effects of extracts of A. tenuifolia using D. rerio embryos and PBL after in vitro exposure. [ABSTRACT FROM AUTHOR]

Introduction: Various studies have shown that the effects of the action of drugs, in addition to having positive effects, they can also provoke negative effects in different organs of the body, where by giving more doses in some cases it can exceed the therapeutic limit and become toxic and produce pathological effects in both experimental animals and humans. Uncontrolled use and drug overdose can lead to macroscopic histopathological changes and give teratogenic, mutagenic and carcinogenic effects. Purpose of the paper: This paper aims to study the effects of some drugs at different stages of embryonic development in chicken eggs. The research of this paper will consist of the toxic effect of drugs and macroscopic and microscopic histopathological changes in certain stages of embryonic development of chicken eggs. Material and method: In the study, fertilized chicken eggs were taken and incubated in the incubator for 21 days of incubation. The eggs were treated with the antibiotic gentamicin at certain stages of embryonic development. The eggs hatched on day thirteen, day fifteen, eighteen and day twentyone. Using the stereomicroscope with the macroscopic and microscopic method were analyzed ontogenetic changes in certain stages of embryonic development. Results: The given dose of the antibiotic gentamicin can have negative effects in certain stages of embryonic development in chicken eggs. The dose given in ampullary form in certain quantities to chicken eggs has inhibited and stagnated the processes of embryonic development at different stages compared to control eggs. Conclusion: The given dose of gentamicin can stagnate embryonic development in certain stages and can provoke changes in certain stages of embryonic development. This phenomenon encourages us to do even more detailed research in this direction to see the effect of the given dose and to analyze what consequences it can provoke overdoses at different stages of embryonic development and within the organism. The lethal dose applied at certain stages of ontogenesis may have lethal consequences for the chick embryo at certain stages of embryonic development. [ABSTRACT FROM AUTHOR]

Glutathione is the body's most abundant endogenous non-enzymatic antioxidant and is used as a substrate for free radical scavenging in the body, especially during ethanol metabolism. This study aims to shift the paradigm of using glutathione as a whitening agent into a potent antioxidant for therapy, particularly for ethanol-induced teratogenesis in the Philippines. Zebrafish embryos were treated with glutathione at various time points of ethanol exposure and concentration. Pre-treatments, co-treatments, and post-treatments with 100 µM glutathione solution were done to assess the most appropriate time point for glutathione intake upon exposure of the embryo to ethanol. Eye diameter and otic vesicle diameter were chosen as morphological parameters because dysmorphogenesis of these organs resembles mammalian fetal alcohol syndrome disorders. For eye diameter, alleviation of microphthalmia by glutathione was seen in pre-treatment (1% ethanol only) and post-treatment (1% & 1.5%) while co-treatment did not exhibit rescue for eye diameter reduction. For otic vesicle diameter, pre- and co-treatment with glutathione did not exhibit any changes in size but post-treatment showed abnormal enlargement suggesting possible teratogenic effect across all ethanol concentrations. The 2,2-diphenylpicryl-1-hydrazine (DPPH) assay was used as a confirmatory test for the free radical scavenging activity (FRSA) of treated tissues. Pre-treatment with GSH at 1% ethanol showed the highest FRSA while post-treatment showed FRSA insignificantly different to controls. This study suggests that glutathione can alleviate oxidative stress in embryo development which may lead to dysmorphogenesis and that supplementation before and after ethanol exposure may be a viable form of therapy for ethanol-induced teratogenesis. [ABSTRACT FROM AUTHOR]

Liane Russell primarily worked in the areas of mammalian genetics, mutagenesis and teratogenesis. Two of her major contributions are the '14-day rule' in radiology and the role of the Y chromosome in mammalian sex determination. Earlier in her career, she studied the effect of radiation on mouse embryonic development. This study highlighted the critical period during development that is most susceptible to the teratogenic effects of radiation. Based on this study, she recommended that whenever possible, exposure of women of child-bearing age to radiation should be restricted to the first two weeks after their last menstrual period to avoid potential damage to their embryos, assuming that the women may be in early pregnancies and unaware of it. This is now known as the '14-day rule'. Later on, along with her colleagues, she showed that in mammals, it is the Y chromosome that determines sex during development and that it is quite different from sex determination in fruitflies, which was well-worked out at that time. This pioneering work has been expanded widely by various researchers to gain an in-depth understanding of the mechanism of sex determination in mammals, especially in humans and its connection with male sterility. Along with her husband and colleagues, she developed the 'Mouse House' at Oak Ridge National Laboratory with the capacity to keep a quarter of a million mice at a time. It lasted for almost 60 years, generating a wealth of information in the fields of basic genetics, cytogenetics, chromosomal behaviour, reproductive biology, mutagenesis and teratogenesis in mammalian development. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) is an endotoxin derived from the cell wall of Gram-negative bacteria. LPS exposure during early gestation is associated with adverse effects on the placenta as well as on developmental outcomes, including embryonic resorption, fetal death, congenital teratogenesis, and fetal growth retardation. This work aimed to explore the adverse effects of LPS injected at an early stage of gestation on the gonads of pregnant rats and the ovaries of their pups and the role of zinc nanoparticles (Zn-NPs) against these adverse effects. Twenty-four pregnant rats were used in this study. They were divided at gestation day 4 into four groups (n = 6): control, Zn-NPs (20 mg/kg orally from gestation day E14 till the end of weaning), LPS (50 µg/kg at gestation days E7 and E9), and LPS + Zn-NPs group. The body weight and placenta weight were recorded at gestational day 16. At postnatal day 21 (weaning), the mothers rats and their offspring were sacrificed and immediately dissected to remove the ovaries and uteri from the mothers and the ovaries from their offspring for subsequent biochemical, histological, and immunohistochemical investigations. The obtained results revealed that LPS exposure during early gestation caused severe histopathological alterations in the placenta, uterus, and ovaries of mothers, as well as in the ovaries of their pups. Also, the uterine and ovarian sections displayed a positive reaction for caspase-3 antibody and a negative reaction for Bcl-2 antibody, which reflects the apoptotic effect of LPS. Additionally, remarkable reductions in the levels of antioxidants (superoxide dismutase and catalase) and significant increases in malondialdehyde (MDA) levels were recorded in the serum of LPS-treated mothers and in the ovarian tissues of their offspring. Further biochemical analysis of the ovarian tissues from LPS-maternally treated offspring showed a significant increase in the levels of caspase-3, TNF-α, and TGF-β1, but a significant decrease in the level of IGF-1. On the other hand, treatment of mothers with Zn-NPs from day 14 of gestation until the weaning day (21st day postnatal) successfully ameliorated most of the deleterious histopathological, immunohistochemical, and biochemical changes induced by LPS. [ABSTRACT FROM AUTHOR]

Aims: Empirical investigations reveal that, in comparison to their typically developing peers, children with histories of prenatal alcohol exposure experience deficits in writing but not drawing skills, both of which require fine motor control. This study examines drawing skills in this clinical group by assessing simple free‐form spiral drawings with indices of spectral features and structural organization. Methods: Children with (n = 15) and without (n = 24) prenatal alcohol exposure used their dominant and nondominant hands to draw a series of spirals using a wireless pen stylus that either provided concurrent visual feedback in the form of a black ink trace or left no visible ink trace of each drawing. Spirals were drawn on a sheet of paper placed on a digitizing table, which facilitated online data acquisition. The data were assessed by power spectral density function analysis and sample entropy analysis. Results: In comparison to their typically developing peers, children with prenatal alcohol exposure produced spirals with a lower mean frequency and less spectral variability. Spirals in the prenatally exposed group were also lower in complexity and structural organization than in the control group. These results occurred independently of hand dominance or the availability of visual feedback. Conclusions: The drawing skills of children with prenatal alcohol exposure have inherent signal characteristics that differ significantly from those produced by typically developing peers. Simple tasks requiring fine motor control may be useful in identifying individuals with fetal alcohol spectrum disorders. [ABSTRACT FROM AUTHOR]

Especially in an area of intensive agricultural production, physicians should be aware of the possible relationship between birth defects, abortion and pesticides. The etiological explanation and therapeutic approach may vary, for example, avoiding environmental and food exposure. Introduction: Areas with higher agricultural production have higher rates of abortion and malformation, probable related to pesticides. Objective: To compare the rates of early abortion and fetal malformation in agricultural and nonagricultural areas. Method: A survey was carried out on fetal deaths in children weighing less than 500 g or gestational age less than 22 weeks and fetal malformations in live births. Results: From 1996 to 2018, there was an increase in the rates of abortion and, albeit to a lesser extent, malformation. The areas of greater agricultural production have higher rates of fetal mortality and malformation than the others. Conclusions: The study suggests that areas with higher use of pesticides have higher rates of abortion and fetal malformations than the others, requiring further observational studies, reducing confounders inherent to the ecological study. [ABSTRACT FROM AUTHOR]

Thyroid hormones (THs) are essential for normal vertebrate development and diverse environmental chemicals are hypothesized to cause developmental toxicity by disrupting TH-mediated signaling. The larval zebrafish (Danio rerio) is an emerging in vivo model of developmental TH disruption; however, the effects of TR antagonism have not yet been studied in zebrafish. NH3, generally considered a potent and specific thyroid hormone receptor (TR) antagonist, has been used in rodents and Xenopus laevis to characterize phenotypes of TR antagonism. The objective of this study is to determine the effects of NH3 on endpoints previously determined to be TH-sensitive in larval zebrafish, specifically teratology and mortality, photomotor behavior, and mRNA expression of TH signaling genes. Zebrafish embryos were exposed to NH3 via static waterborne exposure at concentrations ranging from 0.001 to 10 μM beginning at 6 h post-fertilization (hpf) through 5 days post fertilization (dpf). Significant mortality and teratogenesis was observed at 3, 4, and 5 dpf in zebrafish exposed to NH3 at 10 μM. At concentrations that did not cause significant mortality, NH3 did not exert a consistent antagonistic effect on photomotor behavior assays or mRNA expression when administered alone or in the presence of exogenous T4. Rather, depending on the NH3 concentration and larval age NH3 decreased or increased swimming triggered by transition from light to dark. Similarly, inconsistent antagonistic and agonistic effects on mRNA expression of TH signaling genes were noted following treatment with NH3 alone. NH3 did inhibit T4 (30 nM)-induced gene expression; however, this was only consistently observed at a concentration of NH3 (10 μM) that also caused significant mortality. Collectively, these results suggest that NH3 does not act solely as a TR antagonist in larval zebrafish, but instead exhibits complex modulatory effects on TR activity. These data support the hypothesis that NH3 is a selective thyroid hormone receptor modulator. Further studies of NH3 interactions with the zebrafish thyroid hormone receptor are required to characterize the activity of NH3 in target tissues of the larval zebrafish at the molecular level, highlighting the importance of characterizing NH3 effects in specific models of TH-disruption to better interpret its actions in mechanistic screens of environmental chemicals for TH action.

Abstract Salvia lachnostachys Benth is native to Brazil and has anti-inflammatory, anti-arthritic, cytotoxic, antitumor, and antihyperalgesic activities. The population, including pregnant women, consume this plant to treat pain, inflammation, flu, spasms, insomnia, and depression, mainly. There are no safety reports on the use of this plant during pregnancy. The present study aimed to evaluate the effects of S. lachnostachys ethanolic extract (EESl) on reproductive performance, embryofetal development, and DNA integrity of pregnant female mice. Pregnant females were randomly divided into three experimental groups (n = 10): The Control group was treated with a vehicle, and treatment groups were administered with EESl at 100 and 1000 mg/kg, respectively. Treatment occurred by gavage throughout the gestational period until day 18. Afterward, reproductive performance, embryofetal development, and DNA integrity parameters were evaluated. The results indicated that EESl did not alter any reproductive performance parameters. However, it changed embryofetal outcome through reduced placental weight (EESl 100 mg/kg), decreased fetal weight (EESl 100 and 1000 mg/kg), and increased frequency of small for gestational age fetuses (EESl 1000 mg/kg). In addition, EES1 increased the frequency of external, visceral, and skeletal malformations. Because of the above, it is considered that EESl is not maternotoxic, does not alter reproductive performance, but does alter embryofetal development. Its use in the gestational period is not indicated due to its teratogenic potential.

Alternanthera littoralis P. Beauv is a plant native to Brazil that exhibits various beneficial activities including antioxidant, antibacterial, antifungal, antiprotozoal, anti-hyperalgesic, and anti-inflammatory properties. The aim of this study was to assess the impact of the ethanol extract of Alternanthera littoralis (EEAl) on reproductive outcomes, embryofetal development, and DNA integrity of pregnant female mice. Pregnant Swiss female mice were randomly assigned to three experimental groups (n = 10): controls were administered either 1% Tween 80 (vehicle), EEAl 100 mg/kg or EEAl 1000 mg/kg. Treatment was administered through gavage during the gestational period until day 18. On gestational days 16, 17, and 18, a peripheral blood sample from the tail vein was obtained for DNA integrity analysis (micronucleus test). After the last collection, animals were euthanized by cervical dislocation. Maternal organs and fetuses were collected, weighed, and subsequently analyzed. Reproductive outcome parameters were assessed by measurement of number of implants, live fetuses, and resorptions. Embryonic development was determined by adequacy of weight for gestational age as well as determination of external, visceral, and skeletal malformations. Data demonstrated that EEAl did not produce maternal toxicity at either dose associated with no marked alterations in any of the reproductive outcome parameters including implantation sites, live/dead fetuses ratio, fetal viability, post-implantation losses, resorptions, and resorption rate. However, EEAl 1000 group reduced embryofetal development by lowering placental weight. In addition, there was an increase in the frequency of external and skeletal malformations in the EEAl 1000 group, which could not be attributed to extract exposure as these values were within control levels. Based upon our findings, evidence indicates that the EEAl at the concentrations employed in our study may be considered safe for use during pregnancy and extracts of this plant show potential for development of phytomedicines to be used in pregnancy. [ABSTRACT FROM AUTHOR]

Background Managing a brain tumor during pregnancy is a highly confusing and challenging situation, complicated by several technical, medical, ethical, and sociocultural concerns. The interests of the mother and child are often pitted against each other, for which legal opinion may occasionally be needed. Case Report We present the report of a young lady with intracranial well-differentiated chondrosarcoma who was determined to be pregnant in the immediate postoperative period. We discuss the management of challenges and dilemmas in devising optimum therapy, and the modifications and care required at each step to help safeguard maternal and fetal health. Risks with therapeutic radiation and measures to assess and pre-empt fetal doses that may assist decision-making are also discussed. Conclusion Radiation therapy during pregnancy is challenging and requires multidisciplinary involvement and psychosocial support for the patient and family.

Salvia lachnostachys Benth is native to Brazil and has anti-inflammatory, anti-arthritic, cytotoxic, antitumor, and antihyperalgesic activities. The population, including pregnant women, consume this plant to treat pain, inflammation, flu, spasms, insomnia, and depression, mainly. There are no safety reports on the use of this plant during pregnancy. The present study aimed to evaluate the effects of S. lachnostachys ethanolic extract (EESl) on reproductive performance, embryofetal development, and DNA integrity of pregnant female mice. Pregnant females were randomly divided into three experimental groups (n = 10): The Control group was treated with a vehicle, and treatment groups were administered with EESl at 100 and 1000 mg/kg, respectively. Treatment occurred by gavage throughout the gestational period until day 18. Afterward, reproductive performance, embryofetal development, and DNA integrity parameters were evaluated. The results indicated that EESl did not alter any reproductive performance parameters. However, it changed embryofetal outcome through reduced placental weight (EESl 100 mg/kg), decreased fetal weight (EESl 100 and 1000 mg/kg), and increased frequency of small for gestational age fetuses (EESl 1000 mg/kg). In addition, EES1 increased the frequency of external, visceral, and skeletal malformations. Because of the above, it is considered that EESl is not maternotoxic, does not alter reproductive performance, but does alter embryofetal development. Its use in the gestational period is not indicated due to its teratogenic potential. [ABSTRACT FROM AUTHOR]

Purpose: To review the effects of ionizing radiation to the conceptus and the relationship to the timing of the exposure during pregnancy. To consider strategies that would mitigate potential harms associated with exposure to ionizing radiation during pregnancy. Methods: Data reported in the peer-reviewed literature on entrance KERMA received from specific radiological examinations were combined with published results from experiment or Monte Carlo modeling of tissue and organ doses per entrance KERMA to estimate total doses that could be received from specific procedures. Data reported in the peer-reviewed literature on dose mitigation strategies, best practices for shielding, consent, counseling and emerging technologies were reviewed. Results: For procedures utilizing ionizing radiation for which the conceptus is not included in the primary radiation beam, typical doses are well below the threshold for causing tissue reactions and the risk of induction of childhood cancer is low. For procedures that include the conceptus in the primary radiation field, longer fluoroscopic interventional procedures or multiphase/multiple exposures potentially could approach or exceed thresholds for tissue reactions and the risk of cancer induction must be weighed against the expected risk/benefit of performing (or not) the imaging examination. Gonadal shielding is no longer considered best practice. Emerging technologies such as whole-body DWI/MRI, dual-energy CT and ultralow dose studies are gaining importance for overall dose reduction strategies. Conclusion: The ALARA principle, considering potential benefits and risks should be followed with respect to the use of ionizing radiation. Nevertheless, as Wieseler et al. (2010) state, "no examination should be withheld when an important clinical diagnosis is under consideration." Best practices require updates on current available technologies and guidelines. [ABSTRACT FROM AUTHOR]

The management of pregnant patients with cancer is complex and requires a multidisciplinary team to effectively diagnose, stage, and manage the cancer while also being cognizant of the potential harm that diagnosis and treatment may have on the maternal and fetal well-being. Beyond the complex clinical management of these patients is additional medicolegal consideration. Radiologists play a crucial role in the management of these patients as their knowledge of diagnostic and interventional radiology techniques allows for appropriate and safe imaging for both the mother and fetus. In addition, radiologist are able to educate patient on the different imaging modalities and techniques, thus allowing patients to make informed decisions and maintain autonomy over there care. This article will review safety considerations associated with different imaging modalities, contrast agents, interventional radiology procedures and moderate sedation related to the imaging of pregnant patient with cancer with specific attention paid to the medicolegal aspects. [ABSTRACT FROM AUTHOR]

Since 2014, methods have been described to hatch chick embryos from shell‐less culture after egg contents are first incubated within shells for 55–70 h. The present report describes for the first time a shell‐less culture system for chick embryos from the blastoderm stage to hatching. For the first 69–70 h, egg contents suspended in polymethylpentene kitchen wrap (F.O.R. Wrap, Riken Fabro, Tokyo, Japan) supported in 6.35 or 6.67 cm inside diameter tripods and covered with a disc of immobilized Milli‐Wrap, were rotated back and forth through 90° at 16 or 22 cycles per minute (CPM). Subsequently, the Milli‐Wrap disc was removed and culture tripods were transferred to environmental chambers, which were rocked ±20° through incubation day 8.5 (E8.5). From E9, environmental chambers were maintained in the horizontal position through to hatching with controlled O2 and CO2. To provide supplemental calcium, an aqueous solution containing 100 mg/mL of calcium l‐lactate hydrate was injected through the plastic wrap into the albumen at E9 (2.5 mL) and at E13 (1.0 mL) or E15 (1.0 mL). After incubation for 69–70 h at 16 or 22 CPM, 80%–83% of previously unincubated egg contents yielded apparently normal embryos. Hatch rate of normal embryos resulting from turntable incubation at 16 or 22 CPM was approximately 43%. Of note, egg contents remained in the same culture tripod from blastoderm stage to hatching. This technique may find use as an educational tool and in basic investigations of early embryogenesis, teratogenesis, and gene transfer experiments. Research Highlights: •A novel technique is described for shell‐less culture of chick embryos from the blastoderm stage to hatching.•For the first 69–70 h, egg contents suspended in plastic wrap are covered with a disc of immobilized Milli‐Wrap, then rotated back and forth through 90° at 16 or 22 cycles per minute. [ABSTRACT FROM AUTHOR]

Physiological changes caused by pregnancy promote the formation of gallstones, increasing the risk of acute cholecystitis, cholangitis, and cholelithiasis that occur during pregnancy. Since these diseases can be fatal to both mother and fetus, active treatment is critical. Biliary gallstones are preferably treated using endoscopic retrograde cholangiopancreatography (ERCP), even during pregnancy. While there is no alternative, safer and easier treatment method, complications from ERCP are lethal; therefore, several risks and benefits must be considered. First, various tests should be conducted and considered to determine whether ERCP is necessary. The risk of congenital disabilities from radiation exposure to the fetus during ERCP should be considered and minimized. Furthermore, clinicians should be aware of and use safe anesthetic agents and antibiotics that are safe to use during pregnancy. Finally, ERCPists should be familiar with various technical methods, such as the recently introduced ERCP technique without radiation exposure, stent drainage without complete removal of gallstones in the case of large biliary stones, and removal of biliary stones after childbirth. Pregnancy is not a contraindication for ERCP; as a lifesaving procedure, it should be performed when necessary. Even though the safety of ERCP is considered an acceptable risk in pregnancy, clinicians should continue to try and find safer ways for pregnant women and fetuses being treated for cholelithiasis. [ABSTRACT FROM AUTHOR]

Antecedentes: La Isotretinoína es un análogo de vitamina A aprobado para el tratamiento de acné nodular severo y acné resistente a tratamientos de primera línea. Este tratamiento contrarresta los factores fisiopatológicos principales generadores de acné pero con el potencial riesgo de efectos teratogénicos durante el embarazo. Objetivo: Describir un caso clínico de un paciente con malformaciones múltiples y exposición in útero a Isotretinoína. Caso clínico: Lactante femenina de 1 mes y 9 días de vida, primer embarazo de madre con uso diario de Isotretinoína durante las primeras 6 semanas de gestación y suspendida una vez se conoce el estado de embarazo. Examen físico al nacimiento con dolicocefalia, hipertelorismo, orejas de baja implantación y microtia derecha, hoyuelos preariculares con apéndices rudimentarios en conducto auditivo, cantos pronunciados y micrognatia. En los estudios se detecta hipoplasia del vermix cerebeloso, ductus arterioso y foramen oval permeable. Conclusión: El uso de análogos de vitamina A es frecuente en la práctica clínica, se conocen sus beneficios en el control del acné nodular severo. Es esencial tener claro su alto riesgo de teratogenicidad. Ante la exposición in útero se requiere una búsqueda activa de posibles malformaciones y una consejería genética adecuada.

(1) Background: In the current healthcare environment, there is a large proportion of female staff of childbearing age, so, according to existing conflicting studies, the teratogenic effects that inhalational anesthetics may have on exposed pregnant workers should be assessed. This investigation aims to analyze the teratogenic effects of inhalational anesthetics in conditions of actual use, determining any association with spontaneous abortion or congenital malformations. (2) Methods: A systematic review was carried out according to the PRISMA statement based on PICO (problem of interest–intervention to be considered–intervention compared–outcome) (Do inhalational anesthetics have teratogenic effects in current clinical practice?). The level of evidence of the selected articles was evaluated using the SIGN scale. The databases used were PubMed, Embase, Scopus, Web of Science, Google academic and Opengrey. Primary studies conducted in professionals exposed to inhalational anesthetics that evaluate spontaneous abortions or congenital malformations, conducted in any country and language and published within the last ten years were selected. (3) Results: Of the 541 studies identified, 6 met all inclusion criteria in answering the research question. Since many methodological differences were found in estimating exposure to inhalational anesthetics, a qualitative systematic review was performed. The selected studies have a retrospective cohort design and mostly present a low level of evidence and a low grade of recommendation. Studies with the highest level of evidence do not find an association between the use of inhalational anesthetics and the occurrence of miscarriage or congenital malformations. (4) Conclusions: The administration of inhalational anesthetics, especially with gas extraction systems (scavenging systems) and the adequate ventilation of operating rooms, is not associated with the occurrence of spontaneous abortions or congenital malformations. [ABSTRACT FROM AUTHOR]

First isolated in 1947, the Zika virus was initially connected only to limited or sporadic human infections. In late 2015, the temporal clustering of a Zika outbreak and microcephaly in newborn babies from northeastern Brazil, and the identification of a causal link between the two, led to the characterization of the congenital Zika syndrome. In the wake of the epidemic, several countries from Latin America advised women to postpone pregnancies for periods ranging from six months to two years. These recommendations initiated critical conversations about the challenges of implementing them in societies with limited access to contraception, widespread socioeconomic inequalities, and high rates of unplanned and adolescent pregnancies. The messaging targeted exclusively women, despite a high prevalence of imbalances in the relationship power, and addressed all women as a group, failing to recognize that the decision to postpone pregnancies will impact different women in different ways, depending on their age at the time. Finally, in several countries affected by the Zika epidemic, due to restrictive reproductive policies, legally terminating a pregnancy is no longer an option even at the earliest time when brain malformations as part of the congenital Zika syndrome can be detected by ultrasonography. The virus continued to circulate after 2016 in several countries. Climate change models predict an expansion of the geographical area where local Zika transmission may occur, indicating that the interface between the virus, teratogenesis, and reproductive rights is a topic of considerable interest for medicine, social sciences, and public health for years to come. [ABSTRACT FROM AUTHOR]

Despite the great potential of using positively charged gold nanoparticles (AuNPs) in nanomedicine, no systematic studies have been reported on their synthesis optimization or colloidal stability under physiological conditions until a group at the National Institute of Standards and Technology recently succeeded in producing remarkably stable polyethyleneimine (PEI)-coated AuNPs (Au-PEI). This improved version of Au-PEI (Au-PEI25kB) has increased the demand for toxicity and teratogenicity information for applications in nanomedicine and nanotoxicology. In vitro assays for Au-PEI25kB in various cell lines showed substantial active cytotoxicity. For advanced toxicity research, the frog embryo teratogenesis assay–Xenopus (FETAX) method was employed in this study. We observed that positively-charged Au-PEI25kB exhibited significant toxicity and teratogenicity, whereas polyethylene glycol conjugated AuNPs (Au-PEG) used as comparable negative controls did not. There is a characteristic avidity of Au-PEI25kB for the jelly coat, the chorionic envelope (also known as vitelline membrane) and the cytoplasmic membrane, as well as a barrier effect of the chorionic envelope observed with Au-PEG. To circumvent these characteristics, an injection-mediated FETAX approach was utilized. Like treatment with the FETAX method, the injection of Au-PEI25kB severely impaired embryo development. Notably, the survival/concentration curve that was steep when the standard FETAX approach was employed became gradual in the injection-mediated FETAX. These results suggest that Au-PEI25kB may be a good candidate as a nanoscale positive control material for nanoparticle analysis in toxicology and teratology. [ABSTRACT FROM AUTHOR]

Oculo-auriculo-vertebral spectrum (OAVS) is aetiologically/pathogenetically a heterogeneous disorder. This study focuses on investigating of maternal drug intake during pregnancy in OAVS cases. Our sample was composed of 114 paediatric cases of OAVS. For each patient, an evaluation form seeking identity, medical history, pregnancy and family data, physical/dysmorphological findings and results from complementary tests was applied. Through the analysis of all the forms applied, the history of drug exposure/maternal diseases were retrospectively studied. The age of the population studied ranged between 1 month and 18 years, the majority being male. Regarding otological features, most had pinna involvement: microtia (86.6%); preauricular appendices (41.6%) and preauricular sinus (15.7%). External auditory canal atresia/stenosis was observed in 61.0% of the cases. Most had conductive hearing loss (75.5%) and imaging study revealed middle/inner ear malformations in 21.1% of the cases. Regarding nonotological characteristics, ophthalmological, osteoarticular and cardiac involvement were the 3 most frequently observed. Most cases had no evident cause for the development of anomalies (68.4%). However, in 16.7% a positive family history was identified. A history of drug intake has been elicited in 14.9% of the participants. The drugs intake during pregnancy found in our study were: isotretinoin, fluoxetine, oral contraceptives, levothyroxine, domperidone, enalapril, acyclovir and pseudoephedrine/triprolidine and gestational diabetes in need of treatment. Some drugs are unquestionably associated with the development of malformation, such as isotretinoin, however, the other drugs cannot be underestimated, since their synergistic effect with other environmental agents and genetic background may be in the origin of OAVS. [ABSTRACT FROM AUTHOR]

Pentachloronitrobenzene (PCNB) is an organochlorine fungicide commonly used to treat seeds against seedling infections and controlling snow mold on golf courses. PCNB has been demonstrated to be toxic to living organisms, including fish and several terrestrial organisms. However, only phenotypical deformities have been studied, and the effects of PCNB on early embryogenesis, where primary organogenesis occurs, have not been completely studied. In the current study, the developmental toxicity and teratogenicity of PCNB is evaluated by using frog embryo teratogenesis assay Xenopus (FETAX). Our results confirmed the teratogenic potential of PCNB revealing the teratogenic index of 1.29 during early embryogenesis. Morphological studies revealed tiny head, bent axis, reduced inter ocular distance, hyperpigmentation, and reduced total body lengths. Whole mount in situ hybridization and reverse transcriptase polymerase chain reaction were used to identify PCNB teratogenic effects at the gene level. The gene expression analyses revealed that PCNB was embryotoxic to the liver and heart of developing embryos. Additionally, to determine the most sensitive developmental stages to PCNB, embryos were exposed to the compound at various developmental stages, demonstrating that the most sensitive developmental stage to PCNB is primary organogenesis. Taken together, we infer that PCNB's teratogenic potential affects not just the phenotype of developing embryos but also the associated genes and involving the oxidative stress as a possible mechanism of toxicity, posing a hazard to normal embryonic growth. However, the mechanisms of teratogenesis require additional extensive investigation to be defined completely. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) cause Congenital Zika Syndrome (CZS) in individuals exposed during pregnancy. Studies have shown that ZIKV infection positively regulates the miR-124 expression in neural cells, which leads to a decrease of TFRC, a gene targeted of this miRNA. Both miR-124 and TFRC exhibit a pivotal role in nervous system development. Therefore, in this study we aimed to investigate whether genetic variants that affect the expression of these genes could act together with ZIKV to increase the risk of individuals developing CZS. TFRC rs406271 and MIR-124-1 rs531564 polymorphisms were genotyped, using TaqMan® Genotyping Assays, in a sample of children who were exposed to ZIKV during pregnancy, of whom 40 were born with CZS and 48 without congenital anomalies. We identified that individuals with CZS presented a higher frequency of CG genotype of rs531564 polymorphism in MIR-124-1 (p=0.048), which is associated with increased expression of miR-124. Since ZIKV also upregulates the expression of this miRNA, the presence of CG genotype in individuals exposed to the virus could lead to a scenario of overexpression of miR-124 in the brain. Since teratogenesis is a multifactorial event, this genetic finding could partly explain why such individuals are more susceptible to CZS, considering both the downregulation of important neurodevelopment genes, as well as deregulation of the neurogenesis process. Thus, we provide preliminary evidence about a possible genetic risk factor to CZS and highlight the importance of analyzing functional polymorphisms related to epigenetic modulators of neurodevelopment genes in the context of ZIKV teratogenesis. [ABSTRACT FROM AUTHOR]

Background: Cassia fistula was used traditionally as laxative in pregnant women. Nevertheless, its fetal and maternal effects in pregnancy have not been studied yet. Methods: Oral (Lethal Dose, 50%) LD50 was determined in mice. In addition, a control group, pregnant rats in other 5 experimental groups (n=12) received orally C. fistula aqueous extract (500, 1000 and 2000 mg/kg), tween80 (10%) and distilled water during pregnancy up to the delivery (21-23 days). Some serum indices were evaluated in maternal blood samples after delivery. Histopathologic and histomorphometric evaluations were performed on the selected slices of newborn rats. Results: Anthraquinone‎ content of the aqueous extract was 0.34% w/w. Oral LD50 was obtained more than 5000mg/kg. No abortions and newborn anomalies were observed in groups. The height and weight of the offspring were significantly reduced by the administration of 500, and 2000 mg/kg of extract compared to control. There was no significant change in maternal blood urea and creatinine. Higher concentration (2000mg/kg) led to ALT elevation. ALS levels decreased dose-dependency in treatment groups comparing to control. Histopathological findings showed significant lung vascular congestion, and hypertrophy of heart in group tween80, and significant hepatic parenchymal inflammation in tween80 and 2000mg/kg and 1000mg/kg groups. In all tissues of all groups, malpighian body area and bowman’s capsule space significantly increased compared to the control group. Conclusion: It seems C. fistula extract is safe in pregnancy. Because of confounding role of tween80 in histopathological finding, more research is necessary.

Abstract It has been 40 years since the Chinese Environmental Mutagen Society (CEMS) was established in 1981. Now, it has grown a first-level national society in China, which has 15 professional committees and more than 5000 members. Over the past 40 years, the CEMS has been making many contributions to advance the research of environmental mutagens in China and cultivate professional talents in this field. In the twenty-first century, looking back on what the CEMS has gone through and accomplished, and in light of the major changes in our tasks and mission in the new era, we must plan well for the future, to overcome our shortcomings, to embrace greater development of the CEMS.

ObjectiveAnti-tumor necrosis factor (anti-TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti-TNF agents are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF agent approved for the treatment of rheumatic diseases and/or Crohn's disease, has minimal to no active placental transfer. This analysis was undertaken to evaluate pregnancy outcomes in women receiving CZP, especially those exposed during early pregnancy.MethodsProspective and retrospective data on maternal CZP exposure were extracted from the UCB Pharma safety database through March 6, 2017. Analysis was limited to prospective reports to avoid potential bias associated with retrospective submissions. The numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained.ResultsOf 1,137 prospectively reported pregnancies with maternal exposure to CZP, 528 (including 10 twin pregnancies) had 538 known outcomes: 459 live births (85.3%), 47 miscarriages (8.7%), 27 elective abortions (5.0%), and 5 stillbirths (0.9%). There were 8 major congenital malformations (1.7%) among the 459 infants. First trimester exposure occurred in 367 (81.2%) of 452 pregnancies resulting in 459 live births. Exposure during all 3 trimesters occurred in 201 (44.5%) of 452 pregnancies.ConclusionThis analysis represents the largest cohort of pregnant women exposed to an anti-TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of CZP, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with CZP.

Infections are frequent during pregnancy and their teratogenic role is well documented in Toxoplasmosis, other infections, Rubella, Cytomegalovirus, and Herpes simplex (TORCH). However, the in-utero development effects of the rest of the infections that affect pregnant women are unknown. We described a cohort of patients with major Birth Defects (BD) and the exposure to infections during pregnancy from the information of Congenital Defects Surveillance Programs of two Colombian cities (Bogota and Cali) between 2001 and 2018. We evaluated associations between groups of maternal infections and BD among 3096 cases and 7446 controls that were registered. BD presentation was more frequent as isolated (64.3%), polymalformed (23.2%), and syndromic (12.4%). Infections during pregnancy were present in 52.5% of cases and 44.6% of controls. The most common single infection between cases and controls was vaginal infection. The most common polyinfection was vaginal and urinary tract infection. We found an association between BD and vaginal infections with an odds ratio (OR) 1.18 (CI 1.08–1.30), urinary tract infections OR 1.16 (CI 1.05–1.28), gastrointestinal infections OR 2.06 (IC 1.18–3.59), respiratory infections OR 1.56 (IC 1.28–1.9) and viral infections OR 1.88 (IC 1.18–3.0). Knowing the teratogenic effect of infections is important to extend prevention, screening, timely diagnosis, and appropriate treatment to pregnant women. [ABSTRACT FROM AUTHOR]

Investigation on possible induction of adaptive response (AR) by high-liner energy transfer (LET) particle radiation for protection against low-LET photon radiation-induced detrimental effects has not yet been performed in utero. This study verified if an AR could be induced by high-LET particle radiation from accelerated heavy ions against low-LET X-ray radiation-induced detrimental effects on fetal mice. Total body irradiation of pregnant C57BL/6J mice were performed by delivering a priming dose ranging from 10 mGy to 320 mGy of particle radiation on gestation day 11 followed one day later by a challenge dose at 3500 mGy from X-ray radiation. The monoenergetic beams of carbon, silicon and iron with the LET values of about 15, 55, and 200 KeV/µm, respectively, were examined. Significant suppression by the priming radiation of the detrimental effects (fetal death, malformation, or low body weight) was used as the endpoints for judgment of a successful AR induction on gestation day 18. Existence of AR was not observed. On the other hand, the priming dose of high-LET particle radiation, in some cases, even increased the detrimental effects induced by the challenge dose from low-LET X-ray radiation. Although existence of AR induced by high-LET radiation in cultured mammalian cells in vitro and in certain tissues of laboratory mice in vivo was demonstrated, the present study did not suggest that low dose of high-LET particle radiation could induce an AR in fetal mice in utero under the setup of our experimental system. [ABSTRACT FROM AUTHOR]

First isolated in 1947, the Zika virus was initially connected only to limited or sporadic human infections. In late 2015, the temporal clustering of a Zika outbreak and microcephaly in newborn babies from northeastern Brazil, and the identification of a causal link between the two, led to the characterization of the congenital Zika syndrome. In the wake of the epidemic, several countries from Latin America advised women to postpone pregnancies for periods ranging from six months to two years. These recommendations initiated critical conversations about the challenges of implementing them in societies with limited access to contraception, widespread socioeconomic inequalities, and high rates of unplanned and adolescent pregnancies. The messaging targeted exclusively women, despite a high prevalence of imbalances in the relationship power, and addressed all women as a group, failing to recognize that the decision to postpone pregnancies will impact different women in different ways, depending on their age at the time. Finally, in several countries affected by the Zika epidemic, due to restrictive reproductive policies, legally terminating a pregnancy is no longer an option even at the earliest time when brain malformations as part of the congenital Zika syndrome can be detected by ultrasonography. The virus continued to circulate after 2016 in several countries. Climate change models predict an expansion of the geographical area where local Zika transmission may occur, indicating that the interface between the virus, teratogenesis, and reproductive rights is a topic of considerable interest for medicine, social sciences, and public health for years to come. [ABSTRACT FROM AUTHOR]

Background: HAND2 is a transcription factor important for embryonic development, required for limbs and cardiovascular development. Thalidomide is a drug responsible to a spectrum of congenital anomalies known as Thalidomide Embryopathy (TE), which includes mainly limb and heart defects. It is known that HAND2 interaction with TBX5, an important protein for limbs and heart development, is inhibited by Thalidomide. The aim of this study was to evaluate and characterize HAND2 in the context of TE, and to evaluate its variability in TE individuals. Methods: DNA from 35 TE subjects was extracted from saliva samples and PCR was performed for amplification and Sanger sequencing of HAND2 coding sequence. Results: The analysis showed only one variant; a synonymous variant p.P51 (rs59621536) in exon 1 found in three individuals. Further in silico evaluation confirmed highly HAND2 conservation, being the 3′UTR the most polymorphic region of the gene. Additional computational analyses classified the variant as neutral, without alteration in splicing and miRNA sites. In silico predictions pointed to alteration of two CpG islands adjacent to the variant; however, we did not observe any alterations on the methylation pattern of HAND2 gene in our sample. Moreover, alteration of the binding site of MeCP2, a nuclear protein involved in DNA methylation, was predicted along with alteration in HAND2 mRNA structure. Conclusions: Considering HAND2 being a well conserved gene, further studies with a larger sample should be performed to evaluate the role this gene on genetic susceptibility to TE. [ABSTRACT FROM AUTHOR]

Isotretinoin (ISO), one of vitamin A-derived retinoids, is comparatively the most widely prescribed drug in acne vulgaris pathogenesis. Despite its excellent therapeutic success, the systemic use of this drug showed undesirable serious side effects such as teratogenesis, oxidative stress, and genotoxicity. The uses of retinoids in cancer therapy are limited due to severe adverse reactions. This has led the scientific community to ask for further studies qualifying ISO features and comparing their efficacy and safety. The purpose of this study was to evaluate the cytogenotoxicity of multiple oral doses (5, 10, 15, and 20 mg/kg, daily for seven consecutive days) of ISO in male Sprague-Dawley rats. The micronucleus assay was used to investigate genotoxicity biomarkers such as the percentage of micronucleated polychromatic erythrocytes (%MNPCEs) and the percentage of aberrant cells (%Abc). Another goal was to test the cytotoxicity of the drug by measuring the ratio between PCEs and normochromatic erythrocytes (NCEs) (PCEs/NCEs). In comparison with the control, the three cytogenetic endpoints: %MNPCEs, P/N, and %Abc significantly (P ≤ 0.0017) dose-dependent increase. This suggested genotoxicity and cytotoxicity of the tested ISO doses. Therefore, the therapeutic uses of ISO should be restricted to a very narrow range border. Further studies are needed to shed more light on the safety profile of ISO therapy. [ABSTRACT FROM AUTHOR]

Context: Escitalopram (ESC) use during pregnancy has not been associated with teratogenic effects in fetuses. Aims: To investigate whether ESC administered during pregnancy in mice induces maternal toxicity and teratogenicity in offspring. Methods: Treated mice groups G1 and control G0 (n = 15 per group). Administration of ESC (G1) and saline solution (G0) during pregnancy and euthanasia on the 18th day. Pregnant female mice were treated with ESC (20 mg/kg, via gavage) or saline solution (control group) from the 5th to the 17th day of gestation, when implantation was consolidated. During intraembryonic development until the day before delivery, the drug had an influence on the development of alterations from its maintenance in the uterine environment and its development to the disturbance causing skeletal or visceral malformations. Key results: The intrauterine development parameters that were altered by ESC treatment were: number of resorptions (G0: [0.93 ± 0.24]); G1: [3.33 ± 0.51]), post-implantation loss (G0: [3.95 ± 1.34], G1: [13.75 ± 3.62]) and reduced fetal viability: [97.30 ± 1.00]; G1: [81.09 ± 6.22]). Regarding fetal formation, the treated group had visceral malformations with a significant frequency: cleft palate (G0: [1.0%], G1: [11.86%]) and reduced kidneys (G0: [0%]; G1: [10.17%]). Regarding skeletal malformations, a higher frequency was observed in the following parameters: incomplete supraoccipital ossification (G0: [0%], G1: [15.25]), absence of ribs (G0: [0%], G1 (G0: [0%], G1 [15.25%]) and absence of one or more of the foot phalanges (G0: [1.0%]; 64%]). Conclusion: Results indicate that ESC is an embryotoxic and teratogenic drug. Implications: Until further studies are performed, greater caution is necessary in prescribing the drug to pregnant women. The use of drugs at fertile and gestational ages has an impact on health and embryofetal development. Clear safe usage limits are required when there is a need for continued drug use as in the case of antidepressants, like escitalopram. Escitalopram is described as safe in relation to fetal development. However in animal models of escitalopram use, high rates of abortion and fetal malformations were observed. [ABSTRACT FROM AUTHOR]

The sewage contains toxic chemical compounds that secondary treatment plants do not eliminate, and chlorine is usually added for disinfection before discharge. Chlorine reacts with sewage compounds forming other toxic compounds. The objective of this study was to evaluate the toxicity of treated sewage from a secondary treatment plant using Danio rerio embryos. Three types of treated sewage were tested, one disinfected with chlorine gas (dCl2), another with sodium hypochlorite (dClO), and the plant discharge, which is a mixture of the two sewage disinfection methods (mCl) with a proportion of 70% of dCl2 and 30% of dClO. To estimate the median lethal dilution treated sewage was diluted with dechlorinated tap water at 20, 40, 60, and 80%. Two additional points were made with pure treated sewage and pure dechlorinated tap water. Embryos were exposed 1 h after fertilization (hpf) to 144 hpf. The dCl2 and the mCl were lethal at 60 and 72 hpf, respectively, while the dClO did not show lethality. The embryos exposed to the mCl showed heart failure and slower blood circulation. Those exposed to dCl2 showed teratogenic effects such as pericardial edema and spinal curvature, while those exposed to dClO presented malformations such as incomplete eye development and otolith formation absence. [ABSTRACT FROM AUTHOR]

Gomphrena celosioides is a native Brazilian plant found in the State of Mato Grosso do Sul. It is used in folk medicine to treat kidney diseases, skin diseases, infections, rheumatism, gastrointestinal diseases, and respiratory diseases. It is also used as an abortifacient. To evaluate the effects of the ethanolic extract of Gomphrena celosioides (EEGc) on reproductive performance, embryo development, and chromosome stability, Swiss mice were randomly divided into experimental groups (n = 10). The animals in the control group received the vehicle Tween 80–1% in the proportion of 0.1 mL/10 g of body weight orally, from the first to the 18th gestational day. The animals in the treatment groups received the EEGc (100, 1000, and 2000 mg/kg) from the first to the 18th gestational day. The animals underwent evaluations of their reproductive performance and embryofetal development. The results showed that the EEGc did not change the animals' final weight, weight gain, uterine weight, or net weight gain. The evaluation showed that the absolute and relative organs' weights did not vary between the different experimental groups. In addition, the EEGc did not change the numbers of implants, live fetuses, dead fetuses, or fetal resorptions. There were no differences in post-operative loss rates, implantations, or resorptions, nor were there differences in fetal viability or sex ratio. The use of the EEGc did not result in different frequencies of malformations. In addition, the EEGc did not alter the frequency of chromosomal damage or frequency of micronuclei. Based on our findings, we considered the extract of Gomphrena celosioides to be safe for use during pregnancy, although some parameters indicated caution in its use. [ABSTRACT FROM AUTHOR]

Penicillin, metformin, and aluminum are commonly used substances and their presence in the environment has increased due to their widespread use. In water bodies, the combined presence of xenobiotics leads to additive, synergistic, or antagonistic interactions that significantly modify the toxic response, being more evident in the early stages of development of individuals. These interactions can be evaluated through biomarkers such as the activity and expression of antioxidant enzymes and the production of congenital malformations in exposed organisms. However, little is known about the effects that mixtures of drugs such as penicillin, metformin, and metals such as aluminum can produce on aquatic species that are constantly exposed to these xenobiotics such as common carp. The objective of this study was to determine the toxicity and type of interaction produced on Cyprinus carpio embryos exposed to these pollutants isolated and in mixtures. Here we show that the mixture of these pollutants produces antagonism and synergism at high and low concentrations respectively. In addition, toxicity results show that in embryos subacutely exposed (NOAEL) to the mixture of contaminants, the activity of antioxidant enzymes and their gene expression (PCR-RT) is increased, embryonic development is modified, and teratogenesis occurs. As can be observed, the mixture of the contaminants influenced the toxic response, evidencing the importance of continuing to study interactions; since this is the way, they are usually found in contaminated bodies of water. Highlights: 1. Exposure of Cyprinus carpio embryos to the mixture of metformin, penicillin and aluminum at high concentrations (LC50) produces an antagonistic type of interaction. 2. Exposure of Cyprinus carpio embryos to the mixture of metformin, penicillin and aluminum at sublethal concentrations (NOAEL) produces a synergistic type interaction. 3. Antioxidant enzyme activity of Cyprinus carpio embryos exposed to NOAEL-equivalent concentrations of metformin, penicillin and aluminum is modified by simultaneous exposure to the toxicants. 4. Gene expression of antioxidant enzymes in Cyprinus carpio embryos exposed to NOAEL-equivalent concentrations of metformin, penicillin and aluminum is increased by simultaneous exposure to the toxicants during the first hours of development. 5. The embryonic developmental score of Cyprinus carpio is decreased by simultaneous exposure to metformin, penicillin and aluminum. [ABSTRACT FROM AUTHOR]