ABSTRACT
Fetal development is essential to the human lifespan. As more and more multifetal gestations have been reported recently, clinical diagnosis using magnetic resonance imaging (MRI), which introduced radiofrequency (RF) exposure, raised public concerns. The present study developed two whole-body pregnant models of 31 and 32 gestational weeks (GWs) with twin fetuses and explored RF exposure by 1.5 and 3.0 T MRI. Differences in the relative position of the fetus and changes in fetal weight can cause differences in fetal peak local specific absorption rate averaged over 10 g tissue (pSAR10g). Variation of pSAR10g due to different fetal positions can be ~35%. Numerically, twin and singleton fetal pSAR10g results were not significantly different, however twin results exceeded the limit in some cases (e.g. fetuses of 31 GW at 1.5 T), which indicated the necessity for further research employing anatomically correct twin-fetal models coming from various GWs and particular sequence to be applied.
Subject(s)
Fetus , Magnetic Resonance Imaging , Radio Waves , Humans , Pregnancy , Female , Magnetic Resonance Imaging/methods , Fetus/radiation effects , Fetus/diagnostic imaging , Twins , Gestational Age , Fetal Development/radiation effectsABSTRACT
OBJECTIVE: To investigate the effects of excessive light exposure during gestation on intrauterine development and early growth of neonates in rats. METHODS: Pregnant rats were randomly allocated to three groups: the constant light exposure group, non-light exposure group and control group. Blood samples were collected from the tail vein to analyze melatonin and cortisol levels. Weight, daily food and water consumption were recorded. Uterine weight, placental weight and placental diameter were measured on gestational day 19. Natural birth and neonate growth were also monitored. The expression of NR1D1(nuclear receptor subfamily 1 group D member 1) in offspring's SCN (suprachiasmatic nuclei), liver and adipose tissue was measured. Expression of NR1D1, MT1(melatonin 1â¯A receptor) and 11ß-HSD2 (placental 11ß-hydroxysteroid dehydrogenase type 2) in placenta was also measured. Finally, the expression of MT1 and 11ß-HSD2 in NR1D1 siRNA transfected JEG-3 cells was evaluated. RESULTS: There were no significant differences in maternal weight gain, pregnancy duration, uterine weight, placental body weight, placental diameter, fetal number among three groups. There were no significant differences in weights or lengths of offspring at birth. Compared to other two groups, constant light exposure group showed significantly more rapid growth of offspring in 21st day post-birth. The expression of NR1D1 in SCN, liver and adipose tissues of offspring was not significantly different among three groups. The maternal serum melatonin and cortisol levels of the constant light exposure group were lower and higher than other two groups, respectively. The expressions of NR1D1, MT1 and 11ß-HSD2 were all decreased in placenta of the constant light exposure group. The expression of MT1 and 11ß-HSD2 in JEG-3 cells were decreased after NR1D1 siRNA transfection. CONCLUSION: Excessive light exposure during pregnancy results in elevated cortisol and reduced melatonin exposure to fetuses in uterus, potentially contributing to an accelerated early growth of offspring in rats.
Subject(s)
Light , Melatonin , Placenta , Animals , Female , Pregnancy , Rats , Placenta/radiation effects , 11-beta-Hydroxysteroid Dehydrogenase Type 2 , Fetal Development/radiation effects , Rats, Sprague-Dawley , Hydrocortisone/blood , Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism , Prenatal Exposure Delayed Effects , Receptor, Melatonin, MT1/metabolism , Animals, Newborn , Maternal Exposure , MaleABSTRACT
BACKGROUND: Advancements in medical technologies that utilize ionizing radiation have led to improved diagnosis and patient outcomes, however, the effect of ionizing radiation on the patient is still debated. In the case of pregnancy, the potential effects are not only to the mother but also to the fetus. The aim of this study was to determine if exposure from ionizing radiation during pregnancy alters the development of the cardiovascular and respiratory system of the offspring. MATERIALS AND METHODS: Pregnant C57Bl/6 mice were whole-body irradiated at gestational day 15 with a 137Cs gamma radiation emitting source at 0 mGy (sham), 50 mGy, 300 mGy, or 1000 mGy. Post weaning weight and blood pressure measurements were taken weekly for both male and female pups until euthanasia at 16-17 weeks postnatal age. Immediately following, the trachea was cannulated, and the lungs and heart excised. The lung was then examined to assess respiratory physiological outcomes. RESULTS AND CONCLUSIONS: In utero exposures to 1000 mGy caused significant growth reduction compared to sham irradiated, which remained persistent for both male and female pups. Growth restriction was not observed for lower exposures. There was no significant change in any cardiovascular or respiratory outcomes measured. Overall, intrauterine exposures to ionizing radiation does not appear to significantly alter the development of the cardiovascular and respiratory system in C57Bl/6 pups up to 17 weeks postnatal age.
Subject(s)
Cardiovascular System/radiation effects , Fetus/radiation effects , Maternal Exposure , Prenatal Exposure Delayed Effects , Respiratory System/radiation effects , Animals , Female , Fetal Development/radiation effects , Gamma Rays , Male , Mice , Mice, Inbred C57BL , PregnancyABSTRACT
Exposure to ionizing radiation contributing to negative health outcomes is a widespread concern. However, the impact of low dose and sub-lethal dose radiation (SLDR) exposures remain contentious, particularly in pregnant women who represent a vulnerable group. The fetal programming hypothesis states that an adverse in utero environment or stress during development of an embryo or fetus can result in permanent physiologic changes often resulting in progressive metabolic dysfunction with age. To assess changes in gene expression profiles of glucose/insulin signaling and lipid metabolism caused by radiation exposure in utero, pregnant C57Bl/6J mice were irradiated using a dose response ranging from low dose to SLDR and compared to a Sham-irradiated group. mRNA expression analysis in 16 week old offspring (n = 84) revealed that genes involved in metabolic function including glucose metabolism, insulin signaling and lipid metabolism were unaffected by prenatal radiation exposures up to 300 mGy. However, female offspring of dams exposed to 1000 mGy had upregulated expression of genes contributing to insulin resistance and gluconeogenesis. In a second cohort of mice, the effects of SLDR on fetal programming of hepatic SOCS3 and PEPCK protein expression were assessed. 4 month old female offspring of dams irradiated at 1000 mGy had: 1) increased liver weights, 2) increased hepatic expression of proteins involved in glucose metabolism and 3) increased 18F-fluorodeoxyglucose (FDG) uptake in interscapular brown adipose tissue (IBAT) measured by positron emission tomography (PET) (n = 25). The results of this study indicate that prenatal radiation exposure does not affect metabolic function up to 300 mGy and 1000 mGy may be a threshold dose for sex-specific alterations in glucose uptake and hepatic gene and protein expression of SOCS3, PEPCK, PPARGC1A and PPARGC1B. These findings suggest that SLDR doses alter glucose uptake in IBAT and hepatic gene and protein expression of offspring and these changes may progress with age.
Subject(s)
Adipose Tissue, Brown/growth & development , Fetal Development/genetics , Insulin Resistance/genetics , Liver/metabolism , Adipose Tissue, Brown/radiation effects , Animals , Blood Glucose/metabolism , Carbohydrate Metabolism/genetics , Disease Models, Animal , Fatty Liver/genetics , Fatty Liver/metabolism , Fatty Liver/physiopathology , Female , Fetal Development/radiation effects , Fetus , Glucose/metabolism , Humans , Insulin/metabolism , Lipid Metabolism/genetics , Lipid Metabolism/radiation effects , Liver/pathology , Male , Mice , Pregnancy , Prenatal Exposure Delayed Effects , RadiationABSTRACT
Abstract Objective The aim of this study is to evaluate whether exposure to different environmental lighting conditions affects the reproductive parameters of pregnant mice and the development of their offspring. Methods Fifteen pregnant albino mice were divided into three groups: light/dark, light, and dark. The animalswere euthanized on day 18 of pregnancy following the Brazilian Good Practice Guide for Euthanasia of Animals.Maternal and fetal specimens weremeasured and collected for histological evaluation. Analysis of variance (ANOVA) test was used for comparison of the groups considering p ≤ 0.05 to be statistically significant. Results There was no significant difference in the maternal variables between the three groups. Regarding fetal variables, significant differences were observed in the anthropometric measures between the groups exposed to different environmental lighting conditions, with the highest mean values in the light group. The histological evaluation showed the same structural pattern of the placenta in all groups, which was within the normal range. However, evaluation of the uterus revealed a discrete to moderate number of endometrial glands in the light/dark and light groups, which were poorly developed in most animals. In the fetuses, pulmonary analysis revealed morphological features consistent with the transition from the canalicular to the saccular phase in all groups. Conclusion Exposure to different environmental lighting conditions had no influence on the reproductive parameters of female mice, while the offspring of mothers exposed to light for 24 hours exhibited better morphometric features.
Resumo Objetivo Avaliar se a exposição a diferentes luminosidades no ambiente afeta parâmetros reprodutivos de camundongos fêmeas prenhas e o desenvolvimento de sua prole. Métodos Foram selecionados para o estudo 15 camundongos fêmeas albinas prenhas. Os camundongos foram separados em grupos: luz/escuro, luz e escuro. As fêmeas foram eutanasiadas no 18° dia de gestação, seguindo as recomendações do Guia Brasileiro de Boas Práticas para a Eutanásia de animais. Tanto peças maternas como fetais foram mensuradas e coletadas para avaliação histológica. Foi utilizado o teste de Análise de variantes (Anova) para comparação dos grupos, considerando estatisticamente significativo o valor de p ≤ 0,05. Resultados Ao comparar as variáveis maternas entre os três grupos, não foi encontrada diferença estatística significativa. Em relação às variáveis fetais, houve diferenças estatísticas entre as medidas de antropometria dos grupos submetidos a diferentes luminosidades do ambiente, com melhores valores médios no grupo luz. Histologicamente, a avaliação placentária evidenciou em todos os grupos o mesmo padrão estrutural, com todos dentro da normalidade. No entanto, a avaliação de úteros, tanto do grupo luz/escuro quanto do grupo luz,mostrou quantidade discreta amoderada de glândulas endometriais, com pouco desenvolvimento na maioria dos animais. Nos fetos, análise pulmonar evidenciou características morfológicas compatíveis com a transição da fase canalicular para sacular em todos os grupos. Conclusão As exposições a diferentes luminosidades no ambiente não influenciaram nos parâmetros reprodutivos das fêmeas, entretanto, a ninhada das mães que receberam luz em todo período apresentou melhores medidas morfométricas.
Subject(s)
Animals , Female , Pregnancy , Mice , Lighting/methods , Pregnancy Outcome , Time Factors , Fetal Development/radiation effects , Light , Animals, Newborn/growth & developmentABSTRACT
OBJECTIVE: The aim of this study is to evaluate whether exposure to different environmental lighting conditions affects the reproductive parameters of pregnant mice and the development of their offspring. METHODS: Fifteen pregnant albino mice were divided into three groups: light/dark, light, and dark. The animals were euthanized on day 18 of pregnancy following the Brazilian Good Practice Guide for Euthanasia of Animals. Maternal and fetal specimens were measured and collected for histological evaluation. Analysis of variance (ANOVA) test was used for comparison of the groups considering p ≤ 0.05 to be statistically significant. RESULTS: There was no significant difference in the maternal variables between the three groups. Regarding fetal variables, significant differences were observed in the anthropometric measures between the groups exposed to different environmental lighting conditions, with the highest mean values in the light group. The histological evaluation showed the same structural pattern of the placenta in all groups, which was within the normal range. However, evaluation of the uterus revealed a discrete to moderate number of endometrial glands in the light/dark and light groups, which were poorly developed in most animals. In the fetuses, pulmonary analysis revealed morphological features consistent with the transition from the canalicular to the saccular phase in all groups. CONCLUSION: Exposure to different environmental lighting conditions had no influence on the reproductive parameters of female mice, while the offspring of mothers exposed to light for 24 hours exhibited better morphometric features.
OBJETIVO: Avaliar se a exposição a diferentes luminosidades no ambiente afeta parâmetros reprodutivos de camundongos fêmeas prenhas e o desenvolvimento de sua prole. MéTODOS: Foram selecionados para o estudo 15 camundongos fêmeas albinas prenhas. Os camundongos foram separados em grupos: luz/escuro, luz e escuro. As fêmeas foram eutanasiadas no 18° dia de gestação, seguindo as recomendações do Guia Brasileiro de Boas Práticas para a Eutanásia de animais. Tanto peças maternas como fetais foram mensuradas e coletadas para avaliação histológica. Foi utilizado o teste de Análise de variantes (Anova) para comparação dos grupos, considerando estatisticamente significativo o valor de p ≤ 0,05. RESULTADOS: Ao comparar as variáveis maternas entre os três grupos, não foi encontrada diferença estatística significativa. Em relação às variáveis fetais, houve diferenças estatísticas entre as medidas de antropometria dos grupos submetidos a diferentes luminosidades do ambiente, com melhores valores médios no grupo luz. Histologicamente, a avaliação placentária evidenciou em todos os grupos o mesmo padrão estrutural, com todos dentro da normalidade. No entanto, a avaliação de úteros, tanto do grupo luz/escuro quanto do grupo luz, mostrou quantidade discreta a moderada de glândulas endometriais, com pouco desenvolvimento na maioria dos animais. Nos fetos, análise pulmonar evidenciou características morfológicas compatíveis com a transição da fase canalicular para sacular em todos os grupos. CONCLUSãO: As exposições a diferentes luminosidades no ambiente não influenciaram nos parâmetros reprodutivos das fêmeas, entretanto, a ninhada das mães que receberam luz em todo período apresentou melhores medidas morfométricas.
Subject(s)
Lighting , Pregnancy Outcome , Animals , Animals, Newborn/growth & development , Female , Fetal Development/radiation effects , Light , Lighting/methods , Mice , Pregnancy , Time FactorsABSTRACT
Exposure to environmental toxicants may affect reproduction and development of subsequent generations. This study was aimed at determining the male-mediated F1 effects induced following 8-weeks of subchronic exposure of F0 male mice to bisphenol A (BPA) alone and in a combination with X-rays irradiation (IR) started during their puberty. 4.5 weeks old F0 male mice were exposed to BPA dissolved in ethyl alcohol and diluted in drinking water at the following doses: 5 mg/kg bw, 10 mg/kg bw, 20 mg/kg bw or irradiated with X-rays (0.05 Gy) or exposed to a combination of low doses of both agents (0.05 Gy + 5 mg/kg bw BPA). Immediately after the end of the 8 weeks exposure F0 males were caged with two unexposed females each. Three quarters of the mated females from each group were sacrificed 1 day before expected parturition for examination of prenatal development of the offspring. The remainder of the females from each group were allowed to deliver and rear litters. Pups of exposed males were monitored for postnatal development for 8 weeks. At 8-9 weeks of age 6-8 males from each group of F1 generation were sacrificed to determine sperm count and quality. The current results, compared to the earlier results, showed that exposure of pubescent males to BPA alone or in combination with irradiation may be more damaging to their offspring than the exposure of adult males. The exposure of pubescent males to BPA alone and in combination with irradiation significantly increased the frequency of abnormal skeletons of surviving fetuses, increased the percent of mortality of pups in the F1 generation, reduced the sperm motility of F1 males and may induce obesity. Additionally, the combined BPA and irradiation exposure reduced the number of total and live implantations, whereas the exposure to BPA alone disturbed the male:female sex ratio. The above results may be caused by genetic or by epigenetic mechanisms. Limitation of use of products including BPA, especially by children and teenagers, is strongly recommended.
Subject(s)
Benzhydryl Compounds/toxicity , Endocrine Disruptors/toxicity , Phenols/toxicity , Reproduction/drug effects , Reproduction/radiation effects , X-Rays , Abnormalities, Drug-Induced/pathology , Abnormalities, Radiation-Induced/pathology , Animals , Female , Fetal Development/drug effects , Fetal Development/radiation effects , Growth/drug effects , Growth/radiation effects , Male , Mice , Pregnancy , Semen Analysis , Sexual Maturation , Sperm Count , Sperm Motility/drug effects , Sperm Motility/radiation effects , Testis/drug effects , Testis/pathology , Testis/radiation effectsABSTRACT
El arco aórtico derecho es una entidad rara (prevalencia del 0,1%) que se adscribe a un grupo de malformaciones poco frecuentes y escasamente descritas en la bibliografía en su forma prenatal; sin embargo, no es infrecuente hallarlas como causa de enfermedad respiratoria o digestiva (refractarias a tratamiento) en pacientes adultos, e incluso como procesos vasculares severos con morbimortalidad elevada. Sus variantes pueden condicionar sintomatología compresiva y estar relacionadas con anomalías cardíacas (hasta 90%) y/o con la microdeleción 22q11 (hasta un 46%). El corte ecográfico de 3 vasos-tráquea es fundamental para su diagnóstico prenatal, y tras su detección está indicada una evaluación exhaustiva del corazón fetal, distinguir sus variantes y/o un estudio cromosómico-genético específico. En presencia de otras anomalías el pronóstico es pobre; los casos aislados suelen tener una evolución posnatal oligo o asintomática
Right aortic arch, which belongs to a group of rare malformations, is an uncommon finding (incidence of 0.1%) and few cases of prenatal forms have been described in the literature. Nevertheless, it is not unusual to find these anomalies as the cause of respiratory or digestive disease (refractory to treatment) in adult patients and even as severe vascular processes with high morbidity and mortality. Its variants may cause compressive symptoms and be associated with heart defects (up to 90%) and/or 22q11 microdeletion (up to 46%). The 3 vessels and trachea view is essential for the prenatal diagnosis of right aortic arch. Detection of this condition must be considered an indication for foetal echocardiography, to distinguish its variants, and/or specific chromosome/genetic testing. Isolated right aortic arch is usually asymptomatic, although the outcome of right aortic arch associated with other abnormalities is poor
Subject(s)
Humans , Female , Pregnancy , Adult , Prenatal Diagnosis/methods , Aorta, Thoracic/diagnostic imaging , Prognosis , Pregnancy Complications/diagnostic imaging , Chromosome Disorders/diagnostic imaging , Heart Defects, Congenital/diagnostic imaging , Fetal Development/radiation effects , Echocardiography/methodsABSTRACT
To evaluate the biological effect of the Fukushima Daiichi nuclear disaster, relative differences in the growth of wild Japanese monkeys (Macaca fuscata) were measured before and after the disaster of 2011 in Fukushima City, which is approximately 70 km from the nuclear power plant, by performing external measurements on fetuses collected from 2008 to 2016. Comparing the relative growth of 31 fetuses conceived prior to the disaster and 31 fetuses conceived after the disaster in terms of body weight and head size (product of the occipital frontal diameter and biparietal diameter) to crown-rump length ratio revealed that body weight growth rate and proportional head size were significantly lower in fetuses conceived after the disaster. No significant difference was observed in nutritional indicators for the fetuses' mothers. Accordingly, radiation exposure could be one factor contributed to the observed growth delay in this study.
Subject(s)
Body Weight/radiation effects , Disasters , Fetal Development/radiation effects , Fukushima Nuclear Accident , Head/anatomy & histology , Head/radiation effects , Animals , Biometry , MacacaABSTRACT
El objetivo es analizar los resultados perinatales y obstétricos de las gestaciones en cuya ecografía del primer trimestre se objetivó translucencia nucal incrementada. Obtuvimos 170 translucencias nucales aumentadas (mayor o igual a 3,5 mm), en 62 casos (36,47%) el cariotipo fue normal, en 84 casos (49,41%) fue patológico y en 24 casos (14,11%) no se realizó técnica invasiva. Del total de cariotipos normales (62 casos), 47 gestaciones llegaron a término con parto en nuestro centro y recién nacido normal, dos abortos tras realización de técnica invasiva y hubo diez interrupciones legales del embarazo. Los hallazgos ecográficos encontrados son los siguientes: un caso con megavejiga (2,12%), un caso con onfalocele (2,12%), dos casos de higroma quístico (4,3%), dos hidrops fetales severos, ambos con canal aurícoventricular completo, dos ausencias del hueso nasal (4,3%) y cuatro comunicaciones interventriculares (8,5%). En cuanto al total de translucencia nucal incrementada, 39 casos se correspondieron con trisomía del par 21 (23%), 18 con de trisomía 18 (10,6%), 10 con trisomía 13 (5,9%), 14 con 45XO (8,2%), 1 con 47XXX, (0,7% ), 1 con trisomía 10 (0,7%) y 1 con translocación balanceada 45 XX (t 8;21) (p11;q11)(0,7%). El incremento del grosor de la translucencia nucal entre las 11 y 13 semanas y seis días constituye una expresión fenotípica común de las aneuploidías y una gama de malformaciones fetales y síndromes genéticos. En los fetoseuploides, la prevalencia de las anormalidades fetales y los resultados perinatales adversos aumenta con el incremento de la translucencia nucal (AU)
The objective was to analyze the perinatal and obstetric outcomes of pregnancies, in which increased NT was detected onfirst-trimesterroutine ultrasoundstudy. A total of 170 cases of increased nuchal translucency (equal to or higher than 3.5mm)were detected. Within these cases, 62 (36,47%) had normal karyotype, 84 (49,41%) had aneuplody and 24 (14,11%) were not subjected to invasive techniques. From the group of patients with augmented nuchal translucency and normal karyotype (62), 47 reached full-term delivery at our hospital and the newborns were normal; 2 ended in miscarriage after undergoing an invasive technique, 10 ended in legal termination of pregnancy and 3 did not give birth at our hospital and their data were not available. Ultrasound findings in these patients included: one case of megacystis (2,12%), one case of omphalocele (2,12%), two cases of cystic hygroma (4,3%), two cases of severe hydrops fetalis both with complete AV canal (4,3%), two cases of absent nasal bone (4,3%) and four cases of interventricular communication (IVC) (8,5%). From the total of cases of increased nuchal translucency, 39 corresponded to trisomy-21 (23%); 18 (10,6%) to trisomy-18; 10 to trisomy-13 (5,9%); 14 to Turners syndrome (8,2%), 1 to karyotype 47XXX (0,7%); 1 to trisomy-10 (0,7%) and 1 to balanced translocation 45 XX (t 8;21) (p11;q11) (0,7%). Nuchal translucency thickening between weeks 11 and 13+6 days is a common phenotypical manifestation of a neuploidy and a wide range of fetal malformations and genetic syndromes. In euploid fetuses, the prevalence of fetal abnormal findings and adverse perinatal outcome increases with the nuchal translucency value (AU)
Subject(s)
Humans , Nuchal Translucency Measurement/instrumentation , Nuchal Translucency Measurement/methods , Nuchal Translucency Measurement/radiation effects , Ultrasonography, Prenatal/methods , Prenatal Diagnosis , Nuchal Translucency Measurement/trends , Pregnancy Trimester, First/radiation effects , Retrospective Studies , Fetal Development/radiation effects , Surveys and QuestionnairesABSTRACT
Reliable human data on the effects of prenatal exposure to ionizing radiation are largely based on high-dose exposures. Exposure to low doses may produce effects that are not easily observable at birth, and may persist over the course of the offspring's postnatal life. This is important when considering fetal programing, a phenomenon characterized by changes in offspring phenotype due to a stress experienced in utero. In this review, we briefly summarize the known effects of both high- and low-dose exposure to ionizing radiation during pregnancy in humans. There is a major consensus that the atomic bomb survivors' data shows increased incidence of microcephaly and reductions in IQ of A-bomb survivors, whereas, with diagnostic radiography in utero there is no conclusive evidence of increased cancer risk. Due to the relatively limited data (particularly for low-dose exposures) in humans, animal models have emerged as an important tool to study prenatal effects of radiation. These animal models enable researchers to manipulate various experimental parameters and make it possible to analyze a wider variety of end points. In this review, we discuss the major findings from studies using mouse and rat models to examine prenatal ionizing radiation effects in postnatal development of the offspring. In addition, we broadly categorize trends across studies within three major stages of development: pre-implantation, organogenesis and fetal development. Overall, long-term effects of prenatal radiation exposure (including the possible role on the developmental programing of disease) are important factors to consider when assessing radiation risk, since these effects are of relevance even in the low-dose range.
Subject(s)
Developmental Disabilities/epidemiology , Developmental Disabilities/physiopathology , Prenatal Exposure Delayed Effects/epidemiology , Prenatal Exposure Delayed Effects/physiopathology , Radiation Injuries/epidemiology , Radiation Injuries/physiopathology , Animals , Dose-Response Relationship, Radiation , Embryonic Development/radiation effects , Evidence-Based Medicine , Female , Fetal Development/radiation effects , Humans , Male , Mice , Organogenesis/radiation effects , Pregnancy , Radiation Dosage , Radiation Exposure/statistics & numerical data , RatsABSTRACT
While it is generally believed that fetuses are at high risk of developing cancers, including leukemia, after low doses of radiation, it has been reported that atomic bomb survivors exposed in utero did not show a dose response for translocations in blood T lymphocytes when they were examined at approximately 40 years of age. Subsequent mouse studies confirmed that animals irradiated during the fetal stage did not show evidence of radiation effects in lymphocytes and bone marrow cells when they were examined after reaching adulthood. However, in a study of rat mammary epithelial cells, radiation effects were clearly observed after fetal irradiation. These results indicate that the fate of chromosome aberrations induced in a fetus could vary among different tissues. Here we report on translocation frequencies in mouse thyroid cells, which were irradiated at different stages of fetal development. Cytogenetic examination was conducted using fluorescence n situ hybridization (FISH) painting of chromosomes 1 and 3. Adult mice, 2 Gy X-ray irradiated at 15.5-day-old fetuses (E15.5), showed a higher translocation frequency (30/1,155 or 25.3 × 10-3) than nonirradiated adult controls (0/1,007 or 0.1 × 10-3), and was near that experienced by irradiated mothers and non-pregnant adult females (43/1,244 or 33.7 × 10-3). These results are consistent with those seen in rat mammary cells. However, when fetuses were irradiated at an earlier stage of development (E6.5) before thyroid organogenesis, the resulting observed translocation frequency was much lower (3/502 or 5.8 × 10-3) than that in E15.5 mice. These results suggest that after fetal irradiation, tissue stem cells record radiation effects primarily when the exposure occurs in cells that have been integrated into tissue. Embryonic stem cells that have been damaged prior to integration into the niche may undergo negative selection due to apoptosis, mitotic death or stem cell-niche cell interactions. The implications of these results in interpreting cancer risks after fetal irradiation are also discussed.
Subject(s)
Fetal Development/genetics , Fetal Development/radiation effects , Thyroid Gland/cytology , Thyroid Gland/embryology , Translocation, Genetic/radiation effects , Animals , Dose-Response Relationship, Radiation , Epithelial Cells/metabolism , Epithelial Cells/radiation effects , Female , Lymphocytes/metabolism , Lymphocytes/radiation effects , Male , Mice , Pregnancy , Rats , Spleen/immunology , Thyroid Gland/metabolism , Thyroid Gland/radiation effects , X-Rays/adverse effectsABSTRACT
BACKGROUND: Data on reproductive and developmental effects of extremely low frequency magnetic fields (ELF MFs) are inconclusive. This study tested the hypothesis that maternal exposure to ELF MFs is associated with increased time to pregnancy (TTP), reduced birthweight or small for gestational age (SGA). METHODS: The study cohort consisted of 373 mothers who gave birth between 1990 and 1994 in Kuopio University Hospital, Finland. To increase prevalence of high ELF MF exposure, women living in buildings near known ELF MF sources were included. Maternal exposure to ELF MF before and during pregnancy was assessed with short term measurements in residences and questionnaires. Associations between ELF MF exposure and TTP, low birth weight and SGA were analysed by logistic regression (or linear regression for continuous variables), adjusting for factors known to be associated with the selected pregnancy outcomes, such as maternal smoking, alcohol consumption and socioeconomic status. RESULTS: The MF exposure of the mothers was slightly higher than in Finnish residences in general, but very high exposures (>0.4µT) were rare. No consistent association of ELF MF with TTP, birth weight or SGA was found. CONCLUSIONS: ELF MF exposure is not likely to be associated with TTP or prenatal growth at residential exposure levels that were observable in this study.
Subject(s)
Fetal Development/radiation effects , Magnetic Fields , Maternal Exposure/statistics & numerical data , Time-to-Pregnancy/radiation effects , Cohort Studies , Female , Finland/epidemiology , Humans , PregnancyABSTRACT
Whether radioactive iodine treatment of Graves' disease (GD) during pregnancy will increase pregnancy loss and affect fetal development is still a matter of concern. From May 2005 to December 2015, 2,276 childbearing-age women with GD received iodine-131 treatment in our departments and were retrospectively enrolled in our study. When some of them were found to have been pregnant, their thyroid functions were measured every 4 weeks, in addition, thyroid-stimulating hormone (TSH) was measured 6 weeks after delivery. When necessary, levothyroxine or propylthiouracil (PTU) was given in order to control their TSH levels during pregnancy. Finally, 69 pregnant women (29 ± 3.5 years old) and 1346 women who were not pregnant during the follow-up period were enrolled into this study. They were all hyperthyroid before or during pregnancy. Among 69 pregnant women, the administrated amount of iodine-131 was 254.9 ± 99.9 MBq. Fifty patients became subclinically hypothyroid after treatment and were administrated levothyroxine (55 ± 25 µg/d). Seven patients were diagnosed with subclinical hyperthyroidism during pregnancy and they received PTU (25 ± 12.5 mg/d). Twelve patients with normal thyroid function were also clinically followed. Among 69 women, 63 had a single birth, 3 had dizygotic twins, 2 had two pregnancies and 1 had a single twin birth. Sixty five babies were born full-term, while 9 were premature (4 ± 1 weeks early) with birth weight 3.2 ± 0.5 kg. Six new born babies were considered to be low birth weight infants (< 2.5 kg) while 5 were high birth weight (> 4 kg), but the weights of all the infants were within the normal range. During the period of observation to December 2015, all the infants were found to grow and develop normally. Among 1346 women who were not pregnant were in the further follow-up. Our study found no detrimental effects of the iodine-131 treatment in the pregnant women or their offspring so far.
Subject(s)
Graves Disease/radiotherapy , Iodine Radioisotopes/adverse effects , Maternal Exposure/adverse effects , Abortion, Spontaneous/epidemiology , Adult , Female , Fetal Development/radiation effects , Humans , Iodine Radioisotopes/therapeutic use , Pregnancy , Prenatal Exposure Delayed Effects/epidemiology , Propylthiouracil/therapeutic use , Retrospective Studies , Sex Ratio , Thyrotropin/blood , Thyroxine/therapeutic useABSTRACT
Infertility and adverse pregnancy outcomes are significant public health concerns with global prevalence. Over the past 35 years, research has addressed whether exposure to power-frequency magnetic fields is one of the etiologic factors attributed to these conditions. However, no apparent authoritative reviews on this topic have been published in the peer-reviewed literature for nearly 15 years. This review provides an overview and critical analysis of human studies that were published in the peer-reviewed literature between 2002 and July 2015. Using PubMed, 13 epidemiology studies published during this time frame that concern exposure to magnetic fields and adverse prenatal (e.g., miscarriage), neonatal (e.g., preterm birth or birth defects), and male fertility (e.g., poor semen quality) outcomes were identified. Some of these studies reported associations whereas others did not, and study design limitations may explain these inconsistencies. Future investigations need to be designed with these limitations in mind to address existing research gaps. In particular, the following issues are discussed: (1) importance of selecting the appropriate study population, (2) need for addressing confounding due to unmeasured physical activity, (3) importance of minimizing information bias from exposure measurement error, (4) consideration of alternative magnetic field exposure metrics, and (5) implications and applications of personal exposure data that are correlated within female-male couples. Further epidemiologic research is needed, given the near ubiquitous exposures to power-frequency magnetic fields in the general population.
Subject(s)
Environmental Exposure/adverse effects , Fetal Development/radiation effects , Infertility/etiology , Magnetic Fields/adverse effects , Pregnancy Outcome , Female , Humans , Infant, Newborn , Male , Pregnancy , Prenatal Exposure Delayed Effects , Research Design , RiskABSTRACT
The goal of managing classical Hodgkin lymphoma (cHL) in pregnancy is to obtain good long-term outcomes for both the mother and fetus. Given the excellent outcomes outside of pregnancy, the goal of treatment should remain curative. There remains a tension and debate regarding the timing of chemotherapy, the curative nature of such treatment and the timing of delivery. Moreover, the aim during pregnancy should be to minimize fetal toxicity and optimize perinatal outcomes. The management of cHL within pregnancy was covered within the excellent recent British Committee for Standards in Haematology guidelines, but with necessary brevity. By reviewing the literature over the last 30 years, herein we discuss the options for management during each trimester. Critical organogenesis occurs between 2 and 8 weeks post-conception; during which time the immature fetus is vulnerable to cytotoxic exposure. We discuss the evidence for using ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) and single agent vinblastine in the first trimester. cHL presenting in pregnancy raises complex and difficult ethical dilemmas that can cause anxiety for patients, families and physicians. Decision-making must be multi-disciplinary and holistic, taking into account the patient's wishes, psycho-social and religious beliefs and personal circumstances. Clear communication between the haemato-oncologist, medical obstetrician, nurse specialists, midwives and neonatologists is paramount to a successful outcome.
Subject(s)
Hodgkin Disease/diagnosis , Hodgkin Disease/therapy , Pregnancy Complications, Neoplastic , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Diagnostic Imaging , Disease Management , Female , Fetal Development/drug effects , Fetal Development/radiation effects , Humans , Neoplasm Recurrence, Local , Neoplasm Staging , Pregnancy , Pregnancy Outcome , Pregnancy Trimesters , Time Factors , Treatment OutcomeABSTRACT
A 43-year-old woman (gravida 0, para 0) was diagnosed with thyroid carcinoma and had been receiving radioactive iodine for remnant ablation. Eventually, her pregnant status became apparent; during radiation, she was at 5 gestational weeks. She decided to continue the pregnancy and delivered a boy of 2362 g at 37 gestational weeks. The infant did not present thyroid dysfunction or developmental abnormalities at 2 months of age. The patient was in the early pregnancy stage during radiation, so the fetus did not develop radiation-related damage of the thyroid gland because at this stage, the fetal thyroid does not concentrate iodine. Although the mother had received radioactive iodine during the critical organogenesis period, the fetus did not develop teratogenicity because the radiation was administered at the borderline threshold for teratogenicity. This case suggests the importance of iodine thyroid absorption when considering radiation-related damage to the fetal thyroid gland during early pregnancy.
Subject(s)
Fetal Development/radiation effects , Iodine/adverse effects , Prenatal Exposure Delayed Effects , Radiopharmaceuticals/adverse effects , Adult , Female , Humans , Infant, Newborn , Iodine Radioisotopes/adverse effects , Male , Pregnancy , Pregnancy Trimester, First , Term BirthABSTRACT
OBJECTIVES: The present study determined the effects of mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) exposure on oxidative stress in the brain and liver as well as the element levels in growing rats from pregnancy to 6 weeks of age. METHODS: Thirty-two rats and their offspring were equally divided into three different groups: the control, 900 MHz, and 1800 MHz groups. The 900 MHz and 1800 MHz groups were exposed to EMR for 60 min/d during pregnancy and neonatal development. At the 4th, 5th, and 6th weeks of the experiment, brain samples were obtained. RESULTS: Brain and liver glutathione peroxidase activities, as well as liver vitamin A and ß-carotene concentrations decreased in the EMR groups, although brain iron, vitamin A, and ß-carotene concentrations increased in the EMR groups. In the 6th week, selenium concentrations in the brain decreased in the EMR groups. There were no statistically significant differences in glutathione, vitamin E, chromium, copper, magnesium, manganese, and zinc concentrations between the three groups. CONCLUSION: EMR-induced oxidative stress in the brain and liver was reduced during the development of offspring. Mobile phone-induced EMR could be considered as a cause of oxidative brain and liver injury in growing rats.
Subject(s)
Antioxidants/metabolism , Brain/radiation effects , Electromagnetic Radiation , Growth and Development , Liver/metabolism , Neuroprotective Agents/metabolism , Oxidative Stress/radiation effects , Animals , Brain/metabolism , Female , Fetal Development/radiation effects , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Growth and Development/radiation effects , Malondialdehyde/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/etiology , Prenatal Exposure Delayed Effects/metabolism , Rats , Rats, Wistar , Vitamin E/metabolismABSTRACT
INTRODUCTION: Exposure to low-dose radiation is widespread and attributable to natural sources. However, occupational, medical, accidental, and terrorist-related exposures remain a significant threat. Information on radiation injury to the feto-placental unit is scant and largely observational. We hypothesized that radiation causes trophoblast injury, and alters the expression of injury-related transcripts in vitro or in vivo, thus affecting fetal growth. METHODS: Primary human trophoblasts (PHTs), BeWo or NCCIT cells were irradiated in vitro, and cell number and viability were determined. Pregnant C57Bl/6HNsd mice were externally irradiated on E13.5, and placentas examined on E17.5. RNA expression was analyzed using microarrays and RT-qPCR. The experiments were repeated in the presence of the gramicidin S (GS)-derived nitroxide JP4-039, used to mitigate radiation-induced cell injury. RESULTS: We found that survival of in vitro-irradiated PHT cell was better than that of irradiated BeWo trophoblast cell line or the radiosensitive NCCIT mixed germ cell tumor line. Radiation altered the expression of several trophoblast genes, with a most dramatic effect on CDKN1A (p21, CIP1). Mice exposed to radiation at E13.5 exhibited a 25% reduction in mean weight by E17.5, and a 9% reduction in placental weight, which was associated with relatively small changes in placental gene expression. JP4-039 had a minimal effect on feto-placental growth or on gene expression in irradiated PHT cells or mouse placenta. DISCUSSION AND CONCLUSION: While radiation affects placental trophoblasts, the established placenta is fairly resistant to radiation, and changes in this tissue may not fully account for fetal growth restriction induced by ionizing radiation.
Subject(s)
Fetal Development/radiation effects , Gene Expression Regulation, Developmental/radiation effects , Radiation, Ionizing , Trophoblasts/radiation effects , Animals , Cell Line , Female , Fetal Growth Retardation/etiology , Humans , Mice , Nitrogen Oxides/therapeutic use , Placenta/radiation effects , Pregnancy , Radiation Injuries/drug therapy , Whole-Body Irradiation/adverse effectsABSTRACT
FUNDAMENTO: A Comissão Internacional de Radiologia indica rastreamento com teste de gravidez a todas pacientes do gênero feminino em período fértil que serão submetidas a exame radiológico. Sabe-se que a radiação é teratogênica e que seu efeito é cumulativo. O potencial teratogênico inicia-se com doses próximas às das utilizadas durante esses procedimentos. Não se sabe a prevalência de teste de gravidez positivo em pacientes submetidos a estudo eletrofisiológico e/ou à ablação por cateter em nosso meio. OBJETIVO: Avaliar a prevalência de teste de gravidez positivo em pacientes do gênero feminino encaminhadas para estudo eletrofisiológico e/ou ablação por radiofrequência. MÉTODOS: Estudo transversal com análise de 2.966 pacientes submetidos a estudo eletrofisiológico e/ou ablação por cateter, de junho 1997 a fevereiro 2013, no Instituto de Cardiologia do Rio Grande do Sul. Foram realizados 1.490 exames em mulheres sendo que, destas, 769 encontravam-se em idade fértil. Todas as pacientes foram rastreadas com teste de gravidez no dia anterior ao procedimento. RESULTADOS: Detectou-se positividade do teste em três pacientes, impossibilitando a realização do exame. Observou-se prevalência de 3,9 casos por 1.000 mulheres em idade fértil. CONCLUSÃO: Devido ao baixo custo e à segurança, indica-se a realização de teste de rastreamento para gravidez a todas pacientes em idade fértil, uma vez que o grau de radiação ionizante necessária nesse procedimento é muito próximo ao limiar de teratogenicidade, principalmente no primeiro trimestre, quando os sinais de gestação não são exuberantes.
BACKGROUND: The International Commission of Radiology recommends a pregnancy screening test to all female patients of childbearing age who will undergo a radiological study. Radiation is known to be teratogenic and its effect is cumulative. The teratogenic potential starts at doses close to those used during these procedures. The prevalence of positive pregnancy tests in patients undergoing electrophysiological studies and/or catheter ablation in our midst is unknown. OBJECTIVE: To evaluate the prevalence of positive pregnancy tests in female patients referred for electrophysiological study and/or radiofrequency ablation. METHODS: Cross-sectional study analyzing 2966 patients undergoing electrophysiological study and/or catheter ablation, from June 1997 to February 2013, in the Institute of Cardiology of Rio Grande do Sul. A total of 1490 procedures were performed in women, of whom 769 were of childbearing age. All patients were screened with a pregnancy test on the day before the procedure. RESULTS: Three patients tested positive, and were therefore unable to undergo the procedure. The prevalence observed was 3.9 cases per 1000 women of childbearing age. CONCLUSION: Because of their safety and low cost, pregnancy screening tests are indicated for all women of childbearing age undergoing radiological studies, since the degree of ionizing radiation needed for these procedures is very close to the threshold for teratogenicity, especially in the first trimester, when the signs of pregnancy are not evident.