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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]

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.

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]

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]

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.

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]

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]

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.

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]

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]

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]

El objetivo de la investigación fue determinar el efecto de la exposición prenatal al paraquat (PQ) sobre la formación craneofacial y corporal en ratas BIOU: Wistar. Metodología: estudio experimental, con cincuenta ratas gestantes, distribuidas en cinco grupos: PQ1 y PQ2, recibieron respectivamente 2 y 3 mg/kg de PQ vía subcutánea (SC); vitamina A (control positivo): tratado con 100.000 U.I. de vitamina A vía intragástrica (IG) y grupos controles (agua destilada, vía SC y vía IG). Los tratamientos fueron administrados desde el 6º al 15º día de gestación. Se comparó el peso materno los días 6, 14 y 21. Este último día se practicó laparotomía y determinó el número de implantaciones, reabsorciones, fetos vivos, muertos, peso y talla fetal, y la presencia de alteraciones craneofaciales y corporales. Resultados: no hubo diferencia significativa en la ganancia de peso materno entre los grupos. En los grupos PQ 2mg/Kg y vitamina A se registró, respectivamente, el mayor número de fetos muertos y reabsorciones. El peso y talla de los fetos del grupo vitamina A fue inferior (p

Objective: to study teratogenic effect – the long-term pregnant mother-taken antiepileptic drugs (AEDs) related consequences on paired child mental, social and intellectual development.Material and methods. There were enrolled 80 subjects: 40 children aged 3–9 years and paired mothers suffering from epilepsy for 3 to 35 years. Thirteen and 27 patients had generalized and focal epilepsy, respectively. Seven mothers were in prolonged remission without taking AEDs, 23 were on monotherapy and 10 were on polytherapy. Child research methods: T. Achenbach's clinical CBCL (The Child Behavior Checklist) scales (for children aged under 5 and 6–18 years), a questionnaire for detecting attention deficit hyperactivity disorder and other behavioral disorders modified by N.N. Zavadenko, Wechsler Intelligence Scale for Children (WISC), Luria batteries of neuropsychological tests adapted by J.M. Glozman (for children aged 3–6 and 7–12 years).Results. Neuropsychological study and assessment of intelligence revealed problems in the development of praxis, speech, gnostic functions and memory, as well as disproportion in the development of verbal and non-verbal structures of intelligence. The most common behavioral disorders in children were impulsivity, distraction, difficulties in controlling and organizing movements. The most affected spheres were praxis (motor awkwardness, fine motor disorders of the hands) and speech.Conclusion. The proposed hypothesis that the teratogenic effect of taking AEDs may result in unevenness or delay in developing mental functions in a child was confirmed.

This study was performed according to FDA protocol to evaluate the developmental effects of carvedilol (P-glycoprotein inhibitor), methotrexate (P-glycoprotein substrate) and their combination at therapeutic doses on pregnant rats. Sixty Albino Wistar rats (40 female rats and 20 males) were allocated randomly into four groups orally administered 0.72 mg/kg carvedilol (Cv-treated group [TG]), 0.36 mg/kg methotrexate (MTX-TG), combined doses carvedilol+methotrexate (Cv+MTX-TG), and distilled water (control group) for 2 months in male and 2 weeks in female rats before mating and after copulation, then approval of pregnancy; dosing continued in female groups during pregnancy and lactation periods. Half of the animal groups were euthanized one day before parturition to study prenatal effects, while the other half left for parturition and lactation to study postnatal effect. The results of fertility index recorded in Cv-TG (71.43%), MTX-TG (42.46%) and Cv+MTX-TG (38.47%) was markedly lower than that in control (83.33%) group with lower gestation index was recorded in MTX-TG (80%) and Cv+MTX-TG (60%) than that in Cv-TG (100%) and the control group (100%). The result of resorbed and fetal death recorded a higher percent in Cv-MTX-TG in comparison with MTX-TG and Cv-TG; Cv-MTX-TG fetuses also recorded more anomalies, including hemorrhagic placenta, curved legs, and microcephaly during prenatal period. The postnatal effects showed that the Cv+MTX-TG group recorded a higher decrease in number of pups born, their weight, and increase in number of stillbirths in comparison with methotrexate followed by carvedilol groups in comparison with control group, while the result of viability index recorded (Cv-TG=98.15%, MTX-TG=93.93% and Cv+MTX-TG=76.19%) and lactation index (Cv-TG=77.36%, 83.87% and Cv+MTX-TG=75%). The postnatal anomalies were only recorded in Cv+MTX-TG included skull defect and ulceration, blindness, skin lesion, and alopecia in lactating pups. It is concluded that inhibition of P-gp by carvedilol might increase the placental passage and increase methotrexate concentration in fetal and pups’ tissue with consequence of increase toxic effect of methotrexate both in fetus and pups of Cv+MTX-TG group which might explain the present results of teratogenic study.

Aim: This systematic review aims to assess the safety profile of oxcarbazepine during pregnancy. Methods: Observational studies that included women who took oxcarbazepine anytime during pregnancy were included in our systematic review. The review did not include non‐English articles, reviews, meta‐analyses, case reports and animal studies. Different online sources such as MEDLINE, Cochrane library, Virtual Health Library, etc., were searched for published and unpublished literature. Assessment of the risk of bias in observational studies was carried out using the Newcastle‐Ottawa Scale. The meta‐analyses were performed using a random‐effect model. GRADE was used for the evaluation of the quality of evidence for the primary outcomes. Results: We included 19 cohort studies with a total of 5 071 137 patients, of which 2450 were exposed to oxcarbazepine either as monotherapy or polytherapy. The summary odds ratio (OR) was 1.69 (95% CI, 0.95–2.98) for congenital malformations following in‐utero exposure to oxcarbazepine as compared to the control group of unexposed patients (seven studies [n = 625]), and was 1.19 (95% CI, 0.67–2.12) when compared to those following lamotrigine (LTG) exposure during pregnancy (3 studies [n = 591]). In total, three studies (n = 770) reported the association between in‐utero oxcarbazepine exposure and fetal/perinatal deaths. The meta‐analysis yielded a summary OR of 3.33 (95% CI, 1.70–6.51). Conclusion: Our systematic review will help healthcare providers and guideline developers regarding the treatment of epilepsy and other neurological disorders during pregnancy. More cohort studies with a higher sample size concerning oxcarbazepine use in pregnant patients are required to truly assess the in‐utero safety profile of the drug. [ABSTRACT FROM AUTHOR]

This paper presents the various side effects of radiation including tumor cure probability (TCP) accompanied with frequently severe but transient acute side effects in the surrounding normal (mainly epithelial) tissues and also the risk of late side effects in normal organs, confined to their partial or whole volumes. Besides the local side effects, unexpected exposure to low radiation doses results in the stochastic risk of mutagenic, teratogenic or cancerogenic side effects. In order to minimize the risk of various radiation side effects, some obligatory radiation protection constraints should be restrictively fulfilled. [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 FROM AUTHOR]

Introducción. En la actualidad, la diabetes mellitus representa una de las condiciones médicas que complica el embarazo con mayor frecuencia, lo que afecta el crecimiento y el desarrollo fetal. Objetivo. Determinar las malformaciones esqueléticas y alteraciones en el crecimiento en fetos de ratas Wistar diabéticas. Materiales y métodos. Se utilizó un modelo de diabetes moderada inducida neonatalmente con estreptozotocina (STZ 100 mg/kg de peso corporal, por vía subcutánea) en ratas Wistar. En la adultez, las ratas sanas y diabéticas se aparearon con machos sanos de la misma edad y cepa. El día 20 de gestación se practicó la cesárea bajo anestesia. Se extrajeron los fetos, se pesaron y clasificaron como pequeños (PAG), adecuados (AEG) o grandes (GEG) para la edad gestacional. Los fetos seleccionados se procesaron para el análisis de anomalías esqueléticas y sitios de osificación. Resultados. En la descendencia de las ratas diabéticas, hubo un mayor porcentaje de fetos clasificados como pequeños o grandes y un menor porcentaje de fetos con peso adecuado; el promedio de peso fetal fue menor y había menos sitios de osificación. Se observaron alteraciones en la osificación de cráneo, esternón, columna vertebral, costillas y extremidades anteriores y posteriores; y también, hubo una correlación directa entre el peso y el grado de osificación fetal. Hubo malformaciones congénitas asociadas con la fusión y bifurcación de las costillas, así como cambios indicativos de hidrocefalia, como la forma de domo del cráneo, una amplia distancia entre los parietales y la anchura de las fontanelas anterior y posterior. Conclusión. La diabetes moderada durante la gestación altera el crecimiento y el desarrollo fetal, que se ve afectado tanto por macrosomía y la restricción del crecimiento intrauterino como por malformaciones esqueléticas.

• PVC microplastics affected the arm regeneration efficiency of Ophiactis virens. • PVC microplastics damaged Xenopus laevis intestines and its swimming behaviour. • In consideration of both models, adverse effects were recorded starting from 1 μg mL−1. • The results suggest the combined use of classic and unconventional toxicity models. • Classic toxicity protocols should incorporate histological and behavioral analyses. In this study, we investigated the effects of PVC microplastics (PVC-MPs) using two different animal models: the brittle star Ophiactis virens, and the African clawed frog Xenopus laevis. This is the first study using an environmental relevant sample of PVC-MPs obtained through mechanical fragmentation of a common PVC plumbing pipe. Exposure experiments on brittle star were performed on the adult stage for a duration of 14 days, while those on African clawed frog were performed on the embryogenic developmental stage according to the standardized FETAX protocol (Frog Embryo Teratogenesis Assay-Xenopus). For both models, different endpoints were analysed: mortality, developmental parameters, behavioural assays and histological analyses on target organs by optical and electronic microscopy. Results showed that the concentration of 0.1 μg mL−1 PVC do not cause any adverse effects in both models (common NOEC concentration), while exposure to 1 μg mL−1 PVC adversely affected at least one species (common LOEC concentration). In particular arm regeneration efficiency was the most affected parameters in O. virens leading to a significantly lower differentiation pattern at 1 μg mL−1 PVC. On the contrary, in X. laevis larvae histopathological analyses and behavioural tests were the most susceptible endpoints, exhibiting several abnormal figures and different swimming speed at 10 μg mL−1 PVC. Histopathological analyses revealed a higher abundance of degenerating cells, pyknotic nuclei and cellular debris in the gut of exposed larvae in respect to control. The comparative analyses performed in this work allowed to characterize the specificity of action of the PVC-MPs on the two species, underlining the importance of exploring a large spectrum of endpoints to offer adequate protection in the emerging fields of microplastic research. [ABSTRACT FROM AUTHOR]

Atrazine and Diuron are widely used herbicides. The use of pesticides contaminates the aquatic environment, threatening biodiversity and non-target organisms such as fish. In this study, we investigated the effects of acute exposure for 96 h hours to atrazine and diuron commercial formulations in zebrafish (Danio rerio , wild-type AB) embryos and larvae and adult stages. We observed a significant concentration-dependent survival decrease and hatching delays in animals exposed to both herbicides and in the frequency of malformations compared to the control groups. Morphological defects included cardiac edema, tail reduction, and head malformation. At 7 days post-fertilization (dpf), atrazine exposure resulted in a reduction in the head length at 2, 2.5, and 5 mg/L and increased the ocular distance at 1, 2, 2.5, and 5 mg/L atrazine when compared to controls. At the same age, diuron increased the ocular distance in animals exposed to diuron (1.0 and 1.5 mg/L) and no effects were observed on the head length. We also evaluated a behavioral repertoire in larvae at 7 dpf, and there were no significant differences in distance traveled, mean speed, time in movement, and thigmotaxis for atrazine and diuron when animals were individually placed in a new environment. The cognitive ability of the larvae was tested at 7 dpf for avoidance and optomotor responses, and neither atrazine nor diuron had significant impacts when treated groups were compared to their corresponding controls. Adults' behavior was evaluated 7 and 8 days after the end of the acute herbicide exposure. Exploration of a new environment and associated anxiety-like parameters, social interaction, and aggressiveness were not altered. Our results highlight the need for further studies on the sublethal effects of both herbicides and the consideration of the effects of commercial formulas vs. isolated active ingredients. It also emphasizes the need to take sublethal effects into consideration when establishing the environmental limits of residues. [ABSTRACT FROM AUTHOR]

Atrazine and Diuron are widely used herbicides. The use of pesticides contaminates the aquatic environment, threatening biodiversity and non-target organisms such as fish. In this study, we investigated the effects of acute exposure for 96 h hours to atrazine and diuron commercial formulations in zebrafish (Danio rerio, wild-type AB) embryos and larvae and adult stages. We observed a significant concentration-dependent survival decrease and hatching delays in animals exposed to both herbicides and in the frequency of malformations compared to the control groups. Morphological defects included cardiac edema, tail reduction, and head malformation. At 7 days post-fertilization (dpf), atrazine exposure resulted in a reduction in the head length at 2, 2.5, and 5 mg/L and increased the ocular distance at 1, 2, 2.5, and 5 mg/L atrazine when compared to controls. At the same age, diuron increased the ocular distance in animals exposed to diuron (1.0 and 1.5 mg/L) and no effects were observed on the head length. We also evaluated a behavioral repertoire in larvae at 7 dpf, and there were no significant differences in distance traveled, mean speed, time in movement, and thigmotaxis for atrazine and diuron when animals were individually placed in a new environment. The cognitive ability of the larvae was tested at 7 dpf for avoidance and optomotor responses, and neither atrazine nor diuron had significant impacts when treated groups were compared to their corresponding controls. Adults’ behavior was evaluated 7 and 8 days after the end of the acute herbicide exposure. Exploration of a new environment and associated anxiety-like parameters, social interaction, and aggressiveness were not altered. Our results highlight the need for further studies on the sublethal effects of both herbicides and the consideration of the effects of commercial formulas vs. isolated active ingredients. It also emphasizes the need to take sublethal effects into consideration when establishing the environmental limits of residues.

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. [ABSTRACT FROM AUTHOR]

Background: Cannabinoids including cannabidiol have recognized genotoxic activities but their significance has not been studied broadly epidemiologically across the teratological spectrum. We examined these issues including contextual space-time relationships and formal causal inferential analysis in USA.Methods: State congenital anomaly (CA) rate (CAR) data was taken from the annual reports of the National Birth Defects Prevention Network 2001-2005 to 2011-2015. Substance abuse rates were from the National Survey of Drug Use and Health a nationally representative longitudinal survey of the non-institutionalized US population with 74.1% response rate. Drugs examined were cigarettes, monthly and binge alcohol, monthly cannabis and analgesic and cocaine abuse. Early termination of pregnancy for abortion (ETOPFA) rates were taken from the published literature. Cannabinoid concentrations were from Drug Enforcement Agency. Ethnicity and income data were from the US Census Bureau. Inverse probability weighted (IPW) regressions and geotemporospatial regressions conducted for selected CAs.Results: Data on 18,328,529 births from an aggregated population of 2,377,483,589 for mid-year analyses 2005-2013 comprehending 12,611 CARs for 62 CAs was assembled and ETOPFA-corrected (ETOPFACAR) where appropriate. E-Values for ETOPFACARs by substance trends were elevated for THC (40 CAs), cannabis (35 CAs), tobacco (11 CAs), cannabidiol (8 CAs), monthly alcohol (5 CAs) and binge alcohol (2 CAs) with minimum E-Values descending from 16.55, 1.55x107, 555.10, 7.53x1019, 9.30 and 32.98. Cardiovascular, gastrointestinal, chromosomal, limb reductions, urinary, face and body wall CAs particularly affected. Highest v. lowest substance use quintile CAR prevalence ratios 2.84 (95%C.I. 2.44, 3.31), 4.85 (4.08, 5.77) and 1.92 (1.63, 2.27) and attributable fraction in exposed 0.28 (0.27, 0.28), 0.57 (0.51, 0.62) and 0.47 (0.38, 0.55) for tobacco, cannabis and cannabidiol. Small intestinal stenosis or atresia and obstructive genitourinary defect were studied in detail in lagged IPW pseudo-randomized causal regressions and spatiotemporal models confirmed the causal role of cannabinoids. Spatiotemporal predictive modelling demonstrated strongly sigmoidal non-linear cannabidiol dose-response power-function relationships (P = 2.83x10-60 and 1.61x10-71 respectively).Conclusions: Data implicate cannabinoids including cannabidiol in a diverse spectrum of heritable CAs. Sigmoidal non-linear dose-response relationships are of grave concern. These transgenerational genotoxic, epigenotoxic, chromosomal-toxic putatively causal teratogenic effects strongly indicate tight restrictions on community cannabinoid penetration. [ABSTRACT FROM AUTHOR]

The diagnosis of malignancy, particularly brain tumors, in pregnancy is uncommon but poses a complex dilemma for the management of both the patient and her fetus, as the interplay of disease with the physiological state of pregnancy affects both outcomes. The routine evaluations (symptomatology, imaging, and hormonal assessments) and treatments (surgery, radiation therapy, and chemotherapy) that are commonplace in brain tumor management may need to be omitted or modified keeping in mind the risk to offspring. Multidisciplinary care and extensive prenatal and perinatal counseling and monitoring are essential. In this review, we discuss the available data addressing these issues and factors which may affect considerations of therapeutic abortions, changes in surgical or medical practices, and outcomes thereof. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the effects of the hydroalcoholic extract of flax seed on the teratogenic activity of lamotrigine in the brain of fetuses of rats who had received the drug. In this experimental study, 40 female rats were assigned randomly into four groups and after mating and confirming the vaginal plug, the control animals (group 1) were kept with no intervention, and the other three experimental groups were intraperitoneally injected with respective lamotrigine (75 mg/kg), and 100 and 200 mg/kg of flax seed hydroalcoholic extract. The drug was administered during the organogenesis period. Rats were sacrificed at the 20th day of gestation (one day before term) and fetuses were macroscopically examined, weighed and crown-rump length measured. Fetal brain specimens were processed for H&E and for histological study, using the ImageJ software. Results showed that fetuses of the experimental groups that received lamotrigine had reduced body weight, prefrontal cortical and hippocampal thickness, and pyramidal neurons in the hip­pocampus; Nevertheless, these factors were improved by high-dose administration of flax seed in the experimental group 3 and 4. Our research concludes that lamotrigine negatively influences the development of brain in rats and flax seed has a protective impact on these complications.

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) from the Flaviviridae family, first isolated from the Rhesus monkey in 1947 in Uganda. ZIKV is transmitted by mosquito bites, but vertical and sexual transmissions have also been reported. ZIKV infection during pregnancy causes malformation in the developing fetus, especially central nervous system (CNS) damages, with a noticed microcephaly, making ZIKV be recognized as a teratogenic agent and the responsible for congenital Zika syndrome (CZS). However, it is still a short time since CZS was first reported. Consequently, ZIKV pathogenesis is not entirely elucidated, especially considering that affected children are still under neurodevelopment. Here, we will explore the current knowledge about ZIKV teratogenesis focusing on neurological clinical findings in humans, mechanisms, and experimental models used to understand ZIKV pathophysiology.

This manuscript provides a review focused on embryonic stem cell-based models and their place within the landscape of alternative developmental toxicity assays. Against the background of the principles of developmental toxicology, the wide diversity of alternative methods using pluripotent stem cells developed in this area over the past half century is reviewed. In order to provide an overview of available models, a systematic scoping review was conducted following a published protocol with inclusion criteria, which were applied to select the assays. Critical aspects including biological domain, readout endpoint, availability of standardized protocols, chemical domain, reproducibility and predictive power of each assay are described in detail, in order to review the applicability and limitations of the platform in general and progress moving forward to implementation. The horizon of innovative routes of promoting regulatory implementation of alternative methods is scanned, and recommendations for further work are given.

Physiological development requires precise spatiotemporal regulation of cellular and molecular processes. Disruption of these key events can generate developmental toxicity in the form of teratogenesis or mortality. The mechanism behind many developmental toxicants remains unknown. While recent work has focused on the unfolded protein response (UPR), oxidative stress, and apoptosis in the pathogenesis of disease, few studies have addressed their relationship in developmental toxicity. Redox regulation, UPR, and apoptosis are essential for physiological development and can be disturbed by a variety of endogenous and exogenous toxicants to generate lethality and diverse malformations. This review examines the current knowledge of the role of oxidative stress, UPR, and apoptosis in physiological development as well as in developmental toxicity, focusing on studies and advances in vertebrates model systems.

El inicio del Trastorno Bipolar (TB) típicamente ocurre durante la edad reproductiva, por lo que las mujeres se encuentran especialmente expuestas a padecer episodios durante su edad fértil. El embarazo representa un estado fisiológico que complejiza el abordaje del TB desde el punto de vista clínico, pronóstico y terapéutico. La continuidad del tratamiento farmacológico en este contexto debe considerar el riesgo de la exposición fetal a los psicofármacos así como el riesgo de una reagudización de la enfermedad materna. El litio es considerado como una opción terapéutica de primera línea durante el embarazo. La evidencia acumulada en las últimas décadas sugiere que el riesgo teratogénico del litio es más modesto que el originalmente atribuido. El objetivo de este trabajo es revisar la evidencia disponible respecto de dos determinantes fundamentales de la valoración riesgo-beneficio de las pacientes bipolares embarazadas tratadas con litio: el impacto en el curso clínico recurrente del TB y el riesgo reproductivo asociado a su uso en esta población. Asimismo se discute la evidencia disponible sobre posible teratogénesis neuroconductual asociada al litio.

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.

A wide array of pathogens has the potential to injure the fetus and induce teratogenesis, the process by which mutations in fetal somatic cells lead to congenital malformations. Rubella virus was the first infectious disease to be linked to congenital malformations due to an infection in pregnancy, which can include congenital cataracts, microcephaly, hearing impairment and congenital heart disease. Currently, human cytomegalovirus (HCMV) is the leading infectious cause of congenital malformations globally, affecting 1 in every 200 infants. However, our knowledge of teratogenic viruses and pathogens is far from complete. New emerging infectious diseases may induce teratogenesis, similar to Zika virus (ZIKV) that caused a global pandemic in 2016–2017; thousands of neonates were born with congenital microcephaly due to ZIKV exposure in utero, which also included a spectrum of injuries to the brain, eyes and spinal cord. In addition to congenital anomalies, permanent injury to fetal and neonatal organs, preterm birth, stillbirth and spontaneous abortion are known consequences of a broader group of infectious diseases including group B streptococcus (GBS), Listeria monocytogenes, Influenza A virus (IAV), and Human Immunodeficiency Virus (HIV). Animal models are crucial for determining the mechanism of how these various infectious diseases induce teratogenesis or organ injury, as well as testing novel therapeutics for fetal or neonatal protection. Other mammalian models differ in many respects from human pregnancy including placentation, labor physiology, reproductive tract anatomy, timeline of fetal development and reproductive toxicology. In contrast, non-human primates (NHP) most closely resemble human pregnancy and exhibit key similarities that make them ideal for research to discover the mechanisms of injury and for testing vaccines and therapeutics to prevent teratogenesis, fetal and neonatal injury and adverse pregnancy outcomes (e.g., stillbirth or spontaneous abortion). In this review, we emphasize key contributions of the NHP model pre-clinical research for ZIKV, HCMV, HIV, IAV, L. monocytogenes, Ureaplasma species, and GBS. This work represents the foundation for development and testing of preventative and therapeutic strategies to inhibit infectious injury of human fetuses and neonates.

Introduction: Currently, diabetes mellitus represents one of the medical conditions that more frequently complicates pregnancy affecting the fetus's growth and development. Objective: To determine the skeletal malformations and growth alterations in fetuses of diabetic Wistar rats. Materials and methods: We used a neonatally streptozotocin-induced mild diabetes model (STZ 100 mg/kg body weight - subcutaneously) in Wistar rats. In adulthood, healthy and diabetic rats were mated with healthy males of the same age and strain. On day 20 of gestation, a cesarean was performed under anesthesia. Fetuses were removed, weighed, and classified as small (SPA), adequate (APA), and large (LPA) for the gestational age. Selected fetuses were processed for skeletal anomaly and ossification sites analysis. Results: In the offspring of diabetic rats, there was a higher percentage of fetuses classified as small or large and a lower percentage of fetuses with adequate weight; the fetal weight mean was lower and there were fewer sites of ossification. Alterations were observed in the ossification of the skull, sternum, spine, ribs and fore and hind limbs; and also, there was a direct correlation between fetal weight and ossification degree There were congenital malformations associated with fusion and bifurcation of the ribs, as well as changes indicative of hydrocephaly, such as the dome shape of the skull, a wide distance between parietals, and the width of the anterior and posterior fontanels. Conclusion: Moderate diabetes during pregnancy alters fetal growth and development with macrosomia and intrauterine growth restriction, as well as skeletal malformations. [ABSTRACT FROM AUTHOR]

Keywords: Congenital Zika Syndrome; epidemic; teratogenesis; animal models; viral emergence; birth defects EN Congenital Zika Syndrome epidemic teratogenesis animal models viral emergence birth defects 1 5 5 07/27/21 20210723 NES 210723 Introduction In 2015, an outbreak of Zika virus (ZIKV) infection caused a disproportionate increase in the number of cases of microcephaly in Brazil ([9]). Although two major ZIKV lineages referred to as African lineage (ZIKV SP AF sp ) and Asian lineage (ZIKV SP AS sp ) have been identified, phylogenetic and genomic analyses pointed to those cases as caused by a ZIKV SP AS sp ([11]). In 2016, the Northeast, Southeast, and Central-West regions were severely hit by the ZIKV epidemic accounting for 93.5% of the nationwide reported cases (16.11, 42.98 and 15.8%, respectively), whereas in Southern Brazil, only few cases of ZIKV infection (< 0.5%) had been reported ([30]; [5]; [24]) (Figure 1). In Brazil, ZIKV disease displayed uneven epidemiological outcomes across the regions B ( b [30]; [5]) (Figure 1), thus the epidemic potential of ZIKV to cause disease in humans and new outbreaks cannot be discarded. [Extracted from the article]

Congenital Zika Syndrome (CZS) occurs in up to 42% of individuals exposed to ZIKV prenatally. Deregulation in gene expression and protein levels of components of the p53 signaling pathway, such as p53 and MDM2, due to ZIKV infection has been reported. Here, we evaluate functional polymorphisms in genes of the p53 signaling pathway as risk factors to CZS. Forty children born with CZS and forty-eight children exposed to ZIKV, but born without congenital anomalies were included in this study. Gestational and sociodemographic information as well as the genotypic and allelic frequencies of functional polymorphisms in TP53, MDM2, MIR605 and LIF genes were compared between the two groups. We found children with CZS exposed predominantly in the first trimester and controls in the third trimester (p<0.001). Moreover, children with CZS were predominantly from families with a lower socioeconomic level (p=0.008). We did not find a statistically significant association between the investigated polymorphisms and development of CZS; however, by comparing individuals with CZS and lissencephaly or without lissencephaly, we found a significative difference in the allelic frequencies of the TP53 rs1042522, which is associated with a more potent p53-induced apoptosis (p=0.007). Our findings suggest that the TP53 rs1042522 polymorphism should be better investigate as a genetic risk factor for the development of lissencephaly in children with CZS. [ABSTRACT FROM AUTHOR]

A wide array of pathogens has the potential to injure the fetus and induce teratogenesis, the process by which mutations in fetal somatic cells lead to congenital malformations. Rubella virus was the first infectious disease to be linked to congenital malformations due to an infection in pregnancy, which can include congenital cataracts, microcephaly, hearing impairment and congenital heart disease. Currently, human cytomegalovirus (HCMV) is the leading infectious cause of congenital malformations globally, affecting 1 in every 200 infants. However, our knowledge of teratogenic viruses and pathogens is far from complete. New emerging infectious diseases may induce teratogenesis, similar to Zika virus (ZIKV) that caused a global pandemic in 2016–2017; thousands of neonates were born with congenital microcephaly due to ZIKV exposure in utero , which also included a spectrum of injuries to the brain, eyes and spinal cord. In addition to congenital anomalies, permanent injury to fetal and neonatal organs, preterm birth, stillbirth and spontaneous abortion are known consequences of a broader group of infectious diseases including group B streptococcus (GBS), Listeria monocytogenes , Influenza A virus (IAV), and Human Immunodeficiency Virus (HIV). Animal models are crucial for determining the mechanism of how these various infectious diseases induce teratogenesis or organ injury, as well as testing novel therapeutics for fetal or neonatal protection. Other mammalian models differ in many respects from human pregnancy including placentation, labor physiology, reproductive tract anatomy, timeline of fetal development and reproductive toxicology. In contrast, non-human primates (NHP) most closely resemble human pregnancy and exhibit key similarities that make them ideal for research to discover the mechanisms of injury and for testing vaccines and therapeutics to prevent teratogenesis, fetal and neonatal injury and adverse pregnancy outcomes (e.g., stillbirth or spontaneous abortion). In this review, we emphasize key contributions of the NHP model pre-clinical research for ZIKV, HCMV, HIV, IAV, L. monocytogenes , Ureaplasma species, and GBS. This work represents the foundation for development and testing of preventative and therapeutic strategies to inhibit infectious injury of human fetuses and neonates. [ABSTRACT FROM AUTHOR]

Background: The function of the gestational sac (GS) and the placenta in the closely related processes of embryogenesis and teratogenicity in the first trimester has been minimally described. The prevailing assumption is that direct teratogenic effects are mediated by the critical extraembryonic organ, the placenta, which either blocks or transfers exposures to the foetus. Placental transfer is a dominant mechanism, but there are other paradigms by which the placenta can mediate teratogenic effects. Knowledge of these paradigms and first trimester human developmental biology can be useful to the epidemiologist in the conduct of biomarker-based studies of both maternal and child health.Objective and Rationale: Our aim is to provide a causal framework for modelling the teratogenic effects of first trimester exposures on child health outcomes mediated by the GS and placenta using biomarker data collected in the first trimester. We initially present first trimester human developmental biology for the sake of informing and strengthening epidemiologic approaches. We then propose analytic approaches of modelling placental mechanisms by way of causal diagrams using classical non-embryolethal teratogens (diethylstilboestrol [DES], folic acid deficiency and cytomegalovirus [CMV]) as illustrative examples. We extend this framework to two chronic exposures of particular current interest, phthalates and maternal adiposity.Search Methods: Information on teratogens was identified by a non-systematic, narrative review. For each teratogen, we included papers that answered the five following questions: (i) why were these exposures declared teratogens? (ii) is there a consensus on biologic mechanism? (iii) is there reported evidence of a placental mechanism? (iv) can we construct a theoretical model of a placental mechanism? and (v) can this knowledge inform future work on measurement and modelling of placental-foetal teratogenesis? We prioritized literature specific to human development, the organogenesis window in the first trimester and non-embryolethal mechanisms.Outcomes: As a result of our review of the literature on five exposures considered harmful in the first trimester, we developed four analytic strategies to address first trimester placental mechanisms in birth cohort studies: placental transfer and direct effects on the foetus (DES and maternal adiposity), indirect effects through targeted placental molecular pathways (DES and phthalates), pre-placental effects through disruptions in embryonic and extraembryonic tissue layer differentiation (folic acid deficiency), and multi-step mechanisms that involve maternal, placental and foetal immune function and inflammation (DES and CMV).Wider Implications: The significance of this review is to offer a causal approach to classify the large number of potentially harmful exposures in pregnancy when the exposure occurs in the first trimester. Our review will facilitate future research by advancing knowledge of the first trimester mechanisms necessary for researchers to effectively associate environmental exposures with child health outcomes. [ABSTRACT FROM AUTHOR]