Investigation of teratogenic effects of letrozole on fetal bone development / Investigación de los efectos teratogénicos de letrozol en el desarrollo óseo fetal

SUMMARY: Letrozole is mainly used for the treatment of unexplained infertility, breast cancer and polycystic ovarian syndrome, with secondary use in ovarian stimulation. In cases of unexpected or unknown pregnancy during the use of letrozole, letrozole may cause a teratogenic effect on the fetus. In this reason, in this study, we aimed to determine the effect of letrozole on fetal bone development. In this study, 32 pregnant Wistar albino rats were used. The rats were divided into four groups: Control (saline) and high; 0.3 mg/kg, medium; 0.03 mg/kg, low; 0.003 mg/ kg letrozole. Saline and letrozole were administered in 100 mL solutions by intraperitonaly from day 11 to day 15 of pregnancy. The skeletal system development of fetuses was examined with double skeletal staining, immunohistochemical staining methods and mineral density scanning electron microscopy. A total of 100 fetuses from female rats, 25 in each group, were included in the study. As a result of that, ossification rates were observed to decrease depending on the dose of letrozole in the forelimb limb (scapula, humerus, radius, ulna) and hindlimb (femur, tibia, fibula) limb bones. As a result of the statistical analysis, a statistically significant decrease was found in the ossification rates of all bones between the control group and low, medium, high letrozole groups (p<0.001). Exposure to letrozole during pregnancy adversely affected ossification and bone growth. However, the teratogenic effects of letrozole are unclear. Therefore, it needs to be investigated more extensively.

RESUMEN: Letrozol se usa principalmente para el tratamiento de la infertilidad inexplicable, el cáncer de mama y el síndrome de ovario poliquístico, con estimulación ovárica de uso secundario. En casos de embarazo inesperado o desconocido durante el uso de letrozol, puede causar un efecto teratogénico en el feto. Por esta razón, en este estudio, nuestro objetivo fue determinar el efecto de letrozol en el desarrollo óseo fetal. Se utilizaron 32 ratas albinas Wistar preñadas las cuales se distribuyeron en cuatro grupos: Control (solución salina) y alta; 0,3 mg/kg, medio; 0,03 mg/kg, bajo; 0,003 mg/kg de letrozol. Se administró solución salina y letrozol en soluciones de 100 mL por vía intraperitoneal desde el día 11 hasta el día 15 de la preñez. El desarrollo del sistema esquelético de los fetos se examinó con tinción esquelética doble, métodos de tinción inmunohistoquímica y microscopía electrónica de barrido de densidad mineral. Se incluyeron en el estudio un total de 100 fetos de ratas hembra, 25 en cada grupo. Como resultado, se observó que las tasas de osificación disminuían dependiendo de la dosis de letrozol en los huesos de los miembros torácicos (escápula, húmero, radio, ulna) y de las miembros pélvicos (fémur, tibia, fíbula). Se encontró una disminución estadísticamente significativa en las tasas de osificación de todos los huesos entre el grupo control y los grupos de letrozol bajo, medio y alto (p<0,001). La exposición a letrozol durante la preñez afectó negativamente la osificación y el crecimiento óseo. Sin embargo, los efectos teratogénicos del letrozol no están claros por lo que debe ser investigado más extensamente.

Exposure to wood smoke pollution during pre-gestational period of rat has effects on placenta volume and fetus size / La exposición a la contaminación por humo de leña durante el período pregestacional de la rata tiene efectos sobre el volumen de la placenta y el tamaño del feto

SUMMARY: Studies in humans showed that prenatal exposure to urban air pollution (AP) influences fetal development, and increases the incidence of adverse pregnancy outcomes and some diseases in postnatal life. However, most of these were performed in environments where the main source of environmental particulate matters (PM) emission is diesel combustion by motor vehicles and industries, thereby ignoring the effects produced by wood smoke pollution. We hypothesized that morphological changes in the placenta could contribute to the reduction in fetal size associated with different periods of exposure to AP produced by wood smoke pollution prior to and during pregnancy. The objective of the study was to investigate the quantitative effects of long-term exposure to environmental levels of wood smoke pollution on the macroscopic and microscopic morphology of the placenta in rats. To test this, pregnant rats were exposed during pregestational and gestational periods to wood smoke pollution in indoor and outdoor environments. At 19 days of gestation, the placentas were obtained by caesarean and were prepared for histological, planimetric and stereological analysis. The volume and proportions of the placental compartments were estimated. In addition, stereological estimators in fetal capillaries were calculated in the labyrinth region. Crown rump length, fetus weight and litter weight were influenced by pregestational and gestational exposure periods. Exposure to wood smoke pollution during pregestational period has significant effect on the volume of the placenta, and consequently on fetal height. In conclusion, this study demonstrated that long-term outdoor exposure to wood smoke pollution from residential heating affects fetal health, decreasing the absolute volume of the entire placenta and the placental interface between the mother and fetus, decreasing the total volume of blood vessels present in the labyrinth region ofthe placenta and affecting the size of the fetus.

RESUMEN: Estudios en humanos demostraron que la exposición prenatal a la polución del aire urbano influye en el desarrollo fetal y aumenta la incidencia de resultados adversos de la gestación y algunas enfermedades postnatales. Sin embargo, la mayoría de ellos fueron realizados en entornos donde la principal fuente de emisión de material particulado, fue la combustión de petróleo por vehículos a motor e industrias, ignorando los efectos producidos por el humo de leña producido por la calefacción intradomiciliaria. Hipotetizamos respecto a que los cambios de la placenta contribuirían a la disminución del tamaño fetal relacionado a los períodos de exposición al humo de leña durante los periodos pregestacional y gestacional. El objetivo del estudio fue investigar los efectos cuantitativos de la exposición al humo de leña sobre la morfología macroscópica y microscópica en placenta de ratas. Para probar esto, ratas preñadas fueron expuestas durante los períodos pregestacional y gestacional a la contaminación por humo de leña en ambientes interiores y exteriores. A los 19 días de gestación, las placentas fueron obtenidas por cesárea y fueron preparadas para un análisis histológico, planimétrico y estereológico. Fue estimado el volumen absoluto y las proporciones de los compartimentos placentarios. Además, fueron calculados estimadores estereológicos en capilares fetales del laberinto y trofoblasto. La longitud, el peso del feto y el peso de la camada fueron influenciados por los períodos de exposición pregestacional y gestacional. La exposición a la contaminación por humo de leñá durante el período pregestacional tuvo un efecto significativo en el volumen de la placenta y, en consecuencia, en la altura del feto. En conclusión, este estudio demostró que la exposición a largo plazo al humo de leña afecta la salud del feto, disminuyendo el volumen absoluto de la placenta, además, afecta la interfaz placentaria entre la madre y feto, disminuyendo el volumen total de vasos sanguíneos presentes en la región del laberinto placentario y por consecuente afectando el tamaño del feto.

Avaliação da toxicidade pré-natal: estudo de teratogenicidade do inseticida piriproxifeno em ratos Wistar / Prenatal toxicity assessment: teratogenicity study of the insecticide pyriproxyfen in Wistar rats

Este estudo investigou a toxicidade pré-natal do inseticida piriproxifeno em ratos Wistar, de forma a detectar possíveis alterações no desenvolvimento fetal da progênie exposta durante o período organogênico. Três doses de piriproxifeno (100, 300 e 500mg.kg-1) foram administradas por via oral às progenitoras, do sexto ao 15º dia de gestação. Os fetos foram submetidos à técnica de diafanização modificada descrita por Taylor e Van Dyke, para avaliação de malformações e alterações esqueléticas. Os resultados não demonstraram a ocorrência de toxicidade materna sistêmica ou alterações nos índices reprodutivos avaliados. Malformações ou alterações teratogênicas não foram detectadas, no entanto alterações esqueléticas sugestivas de retardo no desenvolvimento foram observadas especialmente nas doses mais altas testadas (300mg.kg-1 e 500mg.kg-1). Considerando-se a situação complexa de risco para a saúde humana, mostra-se importante a execução de investigações adicionais, de modo a contribuir para a adequada avaliação de risco do piriproxifeno em água potável.(AU)

This study investigated the prenatal toxicity of the insecticide pyriproxyfen in Wistar rats to detect the possible changes in the fetal development of the progeny exposed during the organogenic period. Three doses of pyriproxyfen (100, 300, and 500mg.kg-1) were administered orally to the progenitors, from day 6 to 15 of gestation. The fetuses were processed using the Taylor and Van Dyke modified diaphanization technique to evaluate malformations and skeletal changes. The results did not demonstrate the occurrence of systemic maternal toxicity or changes in the reproductive indexes evaluated. Malformations or teratogenic changes were not detected, however, skeletal changes suggestive of developmental delay were observed, especially in the highest doses tested (300 mg.kg-1 and 500 mg.kg-1). Owing to the potentially complex situation regarding its risk to human health, it is important that further studies be performed to contribute to the risk assessment of the addition of pyriproxyfen in drinking water.(AU)

Drogas ilícitas e gravidez Influência na morfologia fetal / Illicit drugs and pregnancy: influence on fetal morphology

Uso de drogas ilícitas como maconha, cocaína e crack durante a gestação tornou-se problema de saúde pública. O uso de drogas durante a gestação pode provocar má-formação, prematuridade, baixo peso, diminuição do perímetro cefálico, morte súbita. Aumenta a incidência de complicações como deslocamento de placenta, isquemias, infarto e morte. Conhecer os fatores de risco poderá ajudar a elaboração de programas de orientação para as gestantes e melhor conduta para os profissionais da saúde. Este estudo de revisão sistemática pesquisou nas bases de dados Bireme, Scielo, PubMed, Lilacs e Site Up to Date. A seleção levou em conta seus títulos e resumos relacionados ao assunto, no período de 2010 a 2017, utilizando os descritores drogas ilícitas/illict drug, cocaína/cocaine, gravidez/pregnancy e desenvolvimento fetal/fetal morphology. Foram encontrados 64 artigos; desses, foram selecionados 36, os mais recentes, estudos randomizados, relatos de casos e estudos coortes, os quais foram necessários para a construção do texto. Através desta análise observou-se que não existem artigos que falem diretamente sobre os riscos expostos e por qual motivo algumas pessoas, mesmo expostas aos riscos, possuem fetos normais. Portanto, novas pesquisas na área se tornam necessárias para melhor compreensão de como as drogas ilícitas interferem na formação fetal e adotar medidas profiláticas com o intuito de proteger o feto e a gestante, contribuindo para a melhoria da saúde pública.(AU)

Use of illicit drugs such as marijuana, cocaine and crack during pregnancy has become a public health problem. The use of drugs during pregnancy can cause malformation, prematurity, low weight, decreased head circumference, sudden death. It increases the incidence of complications such as placental dislocation, ischaemia, infarction and death. Knowing the risk factors can help the development of programs for counseling pregnant women and better conduct for health professionals. This systematic review study searched the Bireme, Scielo, PubMed, Lilacs and Site Up to Date databases. The selection took into account the titles and summaries related to the subject, from 2010 to 2017, using the descriptors illicit drug / illict drug, cocaine / cocaine, pregnancy / pregnancy and fetal development / fetal morphology. We found 64 articles, of which 36 were selected, the most recent, randomized studies, case reports, cohort studies, which were necessary for the construction of the text. Through this analysis it was observed that there are no articles that speak directly about the risks exposed and for which reason some people even exposed to the risks have normal fetuses. Therefore, new research in the area is necessary to better understand how illicit drugs interfere in fetal formation and adopt prophylactic measures to protect the fetus and pregnant women, contributing to the improvement of public health.(AU)

Tabagismo e gravidez: influência na morfologia fetal / Smoking and pregnancy: influence on fetal morphology

O hábito de fumar durante a gravidez é uma das causas evitáveis de morbidade e mortalidade infantil e materna. A nicotina tem efeitos principalmente no desenvolvimento cerebral e pulmonar fetal. Considerando que apenas uma minoria das mulheres fumantes em idade fértil consegue parar de fumar ao engravidar, o tabagismo entre mulheres jovens é o principal determinante da prevalência do tabagismo durante a gravidez. Este estudo de revisão sistemática pesquisou nas bases de dados Bireme, Scielo, PubMed, Lilacs e Site Up to Date. A seleção levou em conta seus títulos e resumos relacionados ao assunto, no período entre 2010 e 2017, utilizando os descritores tabaco/tobacco, nicotina/nicotine, hábito de fumar/smoking, gravidez/pregnancy e desenvolvimento fetal/fetal morphology. Foram encontrados 75 artigos; destes, foram selecionados 25, os mais recentes estudos randomizados, relatos de casos, estudos coortes e de alto teor teórico, necessários para a construção do texto. Através desta análise, observou-se a necessidade de uma intervenção política mais intensa para desencorajar o hábito de fumar, ocasionar maior impacto das mídias e redes sociais sobre esse assunto e maior atuação dos profissionais da saúde. Portanto, identificar os fatores associados ao tabagismo no período gestacional pode facilitar a implementação de programas que ajudem a diminuir os malefícios sobre a saúde materno-fetal.(AU)

Smoking during pregnancy is one of the preventable causes of infant and maternal morbidity and mortality. Nicotine has effects primarily on fetal brain and lung development. Considering that only a minority of women of childbearing age can quit when they become pregnant, smoking among young women is the main determinant of the prevalence of smoking during pregnancy. This systematic review study searched the Bireme, Scielo, PubMed, Lilacs and Site Up to Date databases. The selection took into account the titles and summaries related to the subject, from 2010 to 2017, using the descriptors tabaco / tobacco, nicotine / nicotine, smoking tuxedo, pregnancy / fetal development and fetal morphology. We found 75 articles, of which 25 were selected, the most recent randomized studies, case reports, cohort studies, and high theoretical content required for the construction of the text. Through this analysis we observed the need for a more intense political intervention that discourages smoking, greater impact of the media and social networks on this subject and greater performance of health professionals. Therefore, identifying the factors associated with smoking in the gestational period may facilitate the implementation of programs that help reduce the harm to maternal-fetal health.(AU)

Influência da deficiência ou suplementação com selênio durante o período gestacional de ratas na suscetibilidade da progênie feminina à carcinogênese mamária / Influence of selenium deficiency or supplementation during rat gestational period on the susceptibility of female offspring to mammary carcinogenesis

Fatores dietéticos como o selênio (Se) são apontados como importantes moduladores do risco de desenvolvimento do câncer de mama. Essa neoplasia pode apresentar sua origem no início do desenvolvimento e, assim, a alimentação materna poderia ter importantes repercussões na programação fetal da doença. A fim de verificar se diferentes concentração de selênio na dieta materna poderiam programar o risco da progênie feminina ao câncer de mama, ratas foram alimentadas com ração contendo 0,15 (CO), 1,0 (SUP) ou 0,05 (DEF) ppm de Se durante a gestação e sua progênie feminina iniciada com DMBA. A progênie do grupo SUP apresentou menor suscetibilidade à carcinogênese, indicado pelo menor número médio e multiplicidade de adenocarcinomas mamários (p< 0,05), enquanto a do grupo DEF apresentou maior suscetibilidade à carcinogênese, indicado pela maior incidência dos mesmos (p< 0,05). Mães do grupo DEF apresentaram menor concentração de Se no sangue (p< 0,05) e sua prole apresentou menor atividade da enzima GPx1 (p< 0,05). Além disso, observou-se na glândula mamária da progênie de 50 dias menor expressão (western blot e qPCR) de ERα, Her-2, EGFR e Ras no grupo SUP em comparação aos grupos CO e DEF (p< 0,05). Analisou-se, ainda, o padrão de metilação global do DNA (HPLC-DAD), expressão das enzimas DNMT1, 3a e 3b (qPCR), o padrão global de modificações pós traducionais em histonas (western blot) e o padrão de metilação da região promotora do gene Erα (modificação com bissulfito e pirossequenciamento) na glândula mamária da progênie de 50 dias. Não houve diferença no padrão de metilação global do DNA e expressão das enzimas DNMTs (p>0,05). Houve aumento na expressão de H4K16 acetilada nos grupos SUP e DEF (p< 0,05). Finalmente, em comparação a progênie do grupo DEF, a do grupo SUP apresentou região promotora de Erα com aumento marginal (p=0,07) na metilação de dois dinucleotídeos CpG. Conclui-se que o consumo de diferentes concentrações de Se na dieta materna tem impacto sobre a suscetibilidade da progênie ao câncer de mama na vida adulta através da modulação da expressão de receptores e oncogenes relacionados ao desenvolvimeto dessa neoplasia, além da influência em processos epigenéticos. Tais resultados apontam para a existência de uma "janela de programação" no início do desenvolvimento sensível a ação do Se, resultando em diminuição do risco de câncer de mama quando suplementado na dieta materna e o inverso quando de sua deficiencia

Based on epidemiological studies and animal models, the essential micronutrient selenium has been highlighted as a promising dietary factor associated to breast cancer risk reduction. Breast cancer may have its origin in early development and thus the maternal diet could have important implications in the fetal programming of the disease. In order to ascertain whether differences in selenium concentration in maternal diet could modulate the susceptibility of female offspring to breast cancer, a biological assay was conducted in which female rats were fed a diet with 0.15 (CO), 1.0 (SUP) or 0.05 (DEF) ppm of selenium during gestational period and the female offspring subjected to a mammary carcinogenesis model induced by DMBA. SUP group offspring presented decreased susceptibility to mammary carcinogenesis, as indicated by lower (p< 0,05) average number and multiplicity od adenocarcinomas, while the DEF group offspring had a greater susceptibility, as indicated by the increase (p< 0,05) in adenocarcinomas incidency. Mothers of the DEF group pesented lower (p< 0,05) Se blood concetrations and their offspring presented lower (p<0,05).GPx1 activity. In addition, there was a decrease (p< 0,05) in ERα, Her-2, EGFR and Ras expression (western blot and qPCR) in the mammary gland of 7 weeks old female SUP group offspring when compared to CO and DEF groups offspring. DNA global methylation pattern (HPLC-DAD), DNMT1, 3a e 3b expression (qPCR), global pattern of post-translational modification in histones (western blot) and methylation status of Erα promoter region (bisulfite modification and pyrosequencing) were also evaluated in the mammary gland of 7 weeks old offspring. There was no diffrence (p>0,05) in DNA global methylation pattern and DNMTs expression. There was an increase in acetilated H4K16 expression in groups SUP and DEF (p< 0,05). Lastly, when compared to DEF offspring, the SUP offspring presented a marginal increase in the methylation of two CpG dinucleotides in the Erα promoter region. In conclusion, the consumption of different selenium concentration in maternal diet plays a role in the progeny's breast cancer susceptibility through the modulation of receptors and oncogenes expression, in addition to modifications in epigenetic patterns. These results indicate the presence of a "programming window" in the beggining of development susceptible to selenium effects, resulting in decreased breast cancer risk when supplemented and the opposite when deficient

Effect of feeding graded doses of Citrinin on clinical and teratology in female Wistar rats.

Citrinin is the one of the well-known mycotoxins, which is possibly spread all over the world. The graded doses of citrinin (1, 3 and 5 ppm CIT in feed) in female Wistar rats 10 weeks prior to mating, during mating and during organogenesis resulted in resorptions and post implantation losses, decreased fetal body weights and crown-rump lengths in fetuses of all groups. Various developmental anomalies recorded in fetuses of treated rats included gross (wrist drop, curled tail, stretched forelimb, subcutaneous haematoma), skeletal (incomplete ossification of skull bones, incomplete fusion of vertebral bodies, complete and partial agenesis of sternaebrae, metacarpals, metatarsals and phalanges, fused ribs and swing out ribs) and visceral (internal and external hydrocephalus, cerebellar hypoplasia, microphthalmia, roundening of heart, contracted kidneys, dilated renal pelvis and cryptorchid testes). The results suggest that CIT has adverse effects on fetal development which may be due to the longer bioavailability of citrinin in the animals.

Importance of iodine in pregnancy

Iodine is an essential constituent of thyroid hormones (TH). TH actively take part in critical periods of brain development during embryonic, fetal and postnatal stages. Therefore the absence of TH or iodine in these critical periods produces an irreversible brain damage. In fact, it is known that iodine deficiency is the leading cause of preventable brain damage worldwide. Because of the physiological adjustments during pregnancy iodine requirements increase significantly from 150 μg per day in non-pregnant adult women to 250 μg per day. Moreover, recent epidemiological studies around the world show that iodine intake during pregnancy is insufficient in many countries, even in developed countries like Australia, Spain and Italy. In the present work an overview of the importance of iodine nutrition during pregnancy is given.

Importancia del yodo en la gestación. El yodo es un nutrimento constituyente indispensable de las hormonas tiroideas (HT). Las HT participan activamente en periodos críticos del desarrollo cerebral durante las etapas embrionaria, fetal y posnatal. Por lo tanto la ausencia o deficiencia de las HT o de yodo en estas etapas del desarrollo produce un daño cerebral irreversible. De hecho, se sabe que la deficiencia de yodo es la principal causa de daño cerebral prevenible en el mundo. Debido a los ajustes fisiológicos propios de la gestación los requerimientos de yodo se incrementan notablemente, pasando de 150 μg al día en la mujer adulta no gestante a 250 μg al día durante el embarazo. Por otra parte, estudios epidemiológicos recientes hechos en todo el mundo muestran que el consumo de yodo durante la gestación es insuficiente en varios países; incluso en países desarrollados como Australia y España e Italia. En la presente revisión se da un panorama general de la importancia del consumo adecuado de yodo durante la gestación.

[ effects of chronic use of imatinib on wistar rat fetuses]

Imatinib mesylate selectively inhibits bcr/abl and other non-specific tyrosine kinases and represents a model of targeted therapy for chronic myeloid leukaemia [CML] as well as gastrointestinal stromal tumors [GIST]. This study was designed to evaluate effects of imatinib on pregnancy and development of fetus. In this experimental study, imatinib was administrated orally at doses of 7, 12, 22, 50 and 100 mg/kg/day and control groups received sterile water. The pregnant rats were subdivided into 2 groups. In group one, the pregnant rats were sacrificed on day 18 of gestation and the number alive and dead of foetuses were checked. The brain of fetuses were fixed in formalin and embedded in paraffin for histological studies. Selected slides were stained with hematoxylin and eosin [H and E]. In group two, the fetuses were allowed to become mature. The effect of drug on learning and memory were assessed by a passive avoidance method using shuttle box apparatus. Histological studies revealed no evidence of teratogenic effects of imatinib on development of frontal and parietal bones. Imatinib given in 100 mg/kg dose caused weight decrease [p<0.001] and increase mortality in fetuses [p<0.01]. Administration of imatinib in 7, 12, 22 and 50 mg/kg doses showed statistically significant reduction in learning and memory of fetuses [p<0.05]. Imatinib can decrease development, learning and memory of fetuses. So, it is recommended that women treated with imatinib avoid becoming pregnant

Toxicity of trigonella foenum graecum [fenugreek] in bone marrow cell proliferation in rat

Fenugreek has a wide range of medical applications and its medicinal use has been clear in several studies, however, few studies are available on effects on haematopoietic stem cell of bone marrow. The goal of the present study was to investigate the effect of Fenugreek on fetal macroscopic diameters and microscopic bone marrow cell histological changes in its teratogenic dosages. Fenugreek decoction was dissolved in 1.5 milliliter distilled water and injected intraperitoneumly in three dosages of 0.8 g/kg, 1.6 g/kg, and 3.2 g/kg for three groups of Wistar female rats mated by Wistar male. For another group [as control group] only 1.5 milliliter distilled water was injected. Bone marrow tissue was prepared from rat fetus and was cut using a microtome and stained with hematoxylin and eosin. Sections were evaluated for changes using light microscope. LD50 for the measurement of teratogenic dosage of fenugreek was 4.1 and 3.5 g/kg in female and male rat, respectively. There was a positive relation between the injected drug dosage and fetal mortality rate. Among all fetal diameters, ear to ear diameter was decreased in groups received Fenugreek decoction. The severity of stem cell histological changes caused by 3.2 g/kg drug injection was lower than distilled water injection and in evaluation of other cells, differences in the severity of histological changes across three groups with different drug dosages and control group was detected. Fenugreek in teratogenic dosages can decrease the severity of bone marrow cell proliferation and increase fetal mortality rate

Effect of prenatal exposure of alcohol in the morphology of developing rat embryo.

The objective this study was to observe the morphological changes in developing rat embryo exposed to alcohol in utero. Virgin female Wistar rats in experimental group (n=15) were given 20% (v/v) alcohol two weeks before mating and throughout the gestational period through oral route. The controls (n=15) were also maintained and were given the tap water. On gestational day 15 (GD15) and 19 (GD19), five rats from each group were sacrificed by cervical dislocation and the abdomen was incised to expose the uterine horn. The number of implantation sites and resorptions were counted and recorded. The body weight and length of the fetuses were also recorded. The litter size and body weight of the newborn were also recorded at the time of birth from the remaining dam. The incidence of resorption was higher in alcohol treated group than in control which was found to be 25% and 8.7% at days 15 and 19 respectively. The body weight and length of fetuses were found to be decreased and was significant at GD15 (p<0.001 for weight and p<0.05 for length). Similarly, the litter size and body weight of newborn were also found to be decreased significantly (p<0.05 for litter size and p<0.01 for body weight). The present study shows that the maternal consumption of alcohol during pregnancy has adverse effect on fetal viability and development of growing embryo.

Avaliação do efeito cumulativo do antimoniato de meglumina sobre a prole de camundongos swiss: ensaio biológico / Evaluate the cumulative effect of meglumine antimoniate on the progeny of swiss mice: biologic assay

OBJETIVOS: Avaliar o efeito do antimoniato de meglumina na transferência materno-fetal na geração F1 (prole de matrizes expostas ao composto), e conseqüências em progênies F2. MÉTODOS: Camundongos fêmeas Swiss foram tratados com antimoniato de meglumina, via subcutânea, com administração diária, do sétimo ao 12º dia de gestação (ddg), na dose equivalente a 100mgSb v/kg peso/dia. O grupo controle recebeu apenas o veículo (água destilada). Após o nascimento da prole (geração F1), 59 fêmeas foram examinadas diariamente para determinação do ciclo estral. Quando determinado o ciclo estro, acasalou-se 18 fêmeas com machos da mesma linhagem. No 18º ddg, as fêmeas foram eutanasiadas por câmara de CO2, o abdômen incisado e o útero exposto, quando avaliou-se os sítios de desenvolvimento embrionário e fetal quanto ao número de reabsorções, fetos vivos e mortos. Todos os fetos e placentas foram pesados para calcular o índice placentário. Três placentas de cada ninhada foram separadas para análise microscópica. RESULTADOS: A exposição ao antimoniato de meglumina não interferiu no ciclo estral dos animais tratados, pelo fato de não alterar o intervalo precoital e o índice de fertilidade. Não foram observadas alterações placentárias em progênies F2. CONCLUSÃO: O antimoniato de meglumina não altera a performance reprodutiva das mães expostas cronicamente. Estes dados sugerem que ocorre uma gradual eliminação do antimoniato de meglumina no organismo materno, sem acarretar danos a proles futuras.

OBJECTIVES: Evaluate the effect of Meglumine Antimoniate on maternal-fetal transference in F1 generations (offspring of dams exposed to the drug), and embryotoxicity in F2 generations. METHODS: Female Swiss mice were treated with daily s.c. injection of Meglumine Antimoniate (100mgSb v/kg bw/day) from day 7 until day 12 of pregnancy. The control group received only the vehicle (distilled water). After birth of offspring (F1 generation), 59 females were examined daily for determination of the estral cycle. When the cycle estrus was determined, males were mated with 18 females of the same lineage. On day 18 of pregnancy, females were euthanasied in a chamber of CO2 and after incision of the abdomen, the uterus was exposed. Then, resorptions as well as living and dead fetuses were evaluated, also the number of embryo/fetal implantation sites. Fetuses and their placenta were weighted to calculate the placental index. Three placentas of each litter were separated for microscopic analysis. RESULTS: Administration of the Meglumine Antimoniate did not interfere in the estral cycle of the treated group, since it did not alter the precoital interval and fertility index. Placenta alterations were not observed in the F2 generations. CONCLUSION: Meglumine Antimoniate did not interfere in the reproductive performance, after chronic exposition of dams. Data suggest that there is a gradual elimination of Meglumine Antimoniate by the maternal organism without damaging the future offspring.

Petroleum ether extract of Cissus quadrangularis (LINN) stimulates the growth of fetal bone during intra uterine developmental period: a morphometric analysis

OBJECTIVE: The aim of the present study was to analyze the effect Cissus quadrangularis plant petroleum ether extract on the development of long bones during the intra-uterine developmental stage in rats. METHODS: Pregnant rats (n=12) were randomly assigned into either a control group (n=6) or a Cissus quadrangularis treatment (n=6) group. Pregnant rats in the Cissus quadrangularis group were treated with Cissus quadrangularis petroleum ether extract at a dose of 500 mg/kg body weight from gestation day 9 until delivery. The animals in the control group received an equal volume of saline. Newborn pups were collected from both groups for alizarin red S - alcian blue staining to differentiate ossified and unossified cartilage. The ossified cartilage (bone) was morphometrically analyzed using Scion image software. RESULTS: Morphometric analysis revealed that the percentage of the total length of ossified cartilage (bone) in pups born to treated dams was significantly higher (P<0.001- -0.0001) than that of the control group. CONCLUSION: The results of the present study suggest that maternal administration of Cissus quadrangularis petroleum ether extract during pregnancy can stimulate the development of fetal bone growth during the intra-uterine developmental period.

Teratogenicity of Asparagus racemosus Willd. root, a herbal medicine.

Asparagus racemosus (AR) is a herb used as a rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.

Penicillin - streptomycin in the culture medium during in vitro maturation [IVM] of bovine oocytes affects nuclear maturation and subsequent embryo development

Standard concentrations of antibiotics in culture media are thought to have no detectable toxic effects on the cultured cells. However, since antibiotics are biologically active substances, the possibility that they interfere to some extent with cellular processes occurring in the cultured cells can not always be totally excluded. This study, therefore, was conducted to assess whether the presence of penicillin-streptomycin [pen-strep] during in vitro maturation [IVM] of bovine cumulus oocytes complexes [COCs] affect nuclear and cytoplasmic maturation and subsequent embryo development. Bovine COCs were matured at 39oC in a humidified atmosphere with 5 percent CO[2] in air for 24 h in: 1- culture medium M199 supplemented with 10 percent FCS [Fetal calf serum], 0.05 lU/ml rhFSH [recombinant human FSH] and 100 units penicillin and 100 fig streptomycin/ ml. 2- culture medium Ml99 without FCS and rhFSH in the presence of pen-strep. Cultures without antibiotics served as control. Six series of experiments, each consisted of at least 3 replicates, were performed. In vitro maturation in the presence of pen-strep in culture medium supplemented with FCS and rhFSH significantly [P<0.05] increased the percentage of Mil oocytes, however, when the COCs were divided, on the basis of appearance of the cumulus investment, into bright and dark groups, this effect was less obvious in both types of COCs, 76 percent vs. 72 percent in bright COCs [P =0.149] or 83 percent vs. 80 percent in dark COCs [P=0.296] in treated and control groups respectively. The percentage of oocytes with type III of cortical granules [CGs] distribution was not affected in the presence of pen-strep. The COCs expansion after IVM was not affected by the presence of antibiotics in culture medium. The subsequent embryo development of IVM/IVF produced ova, which were exposed to pen-strep during IVM, was significantly [P<0.05] decreased with respect to blastocyst formation by day 9. In vitro maturation in the presence of pen-strep in culture medium without FCS and rhFSH had no significant [P=0.402] effect on nuclear maturation. The results indicate that the nuclear maturation of bovine oocytes was .positively influenced by the presence of pen-strep during IVM when the culture media was supplemented with FCS and rhFSH. Moreover, despite of no notable effect of pen-strep on CGs distribution the subsequent embryo development was negatively influenced by the presence of pen-strep

Desenvolvimento pré-embrionário em ratas tratadas com oxcarbazepina nos quatro primeiros dias após a inseminaçäo / Pre-embryo development in rats treated with oxcarbazepine in the first four days after insemination

A oxcarbazepina é uma droga antiepiléptica de alta eficácia e poucos efeitos colaterais, mas pouco estudada quanto a seus efeitos durante a gestaçäo humana e animal. OBJETIVO: Verificar se a administraçäo de oxcarbazepine em ratas, nos quatro primeiros dias após a inseminaçäo, altera a viabilidade ou o desenvolvimento do pré-embriäo. MÉTODOS: Ratas Wistar foram tratadas com 20 ou 200 mg de oxcarbazepina/ Kg de peso corporal, via gástrica, nos dias 1, 2, 3, ou 4 a partir da inseminaçäo ou, consecutivamente, do 1º ao 4º. Os pré-embriões foram coletados no quinto dia, visando verificar a quantidade e o desenvolvimento até a fase de blastocisto expandido. O peso corporal materno e sinais como pelos eriçados e alteraçäo de atividade locomotora foram anotados para verificar indícios de toxicidade materna. Número de corpos lúteos e peso de ovários foram anotados com vistas à capacidade reprodutiva do animal. RESULTADOS: Näo ocorreram perdas de pesos corporais maternos e nenhuma alteraçäo física indicativa de desconforto para as ratas. Peso de ovários e número de corpos lúteos näo diferiram entre tratados e controles. O número médio de pré-embrioes por mäes, o índice de perdas embrionárias, a proporçäo de blastocistos expandidos com relaçäo ao total de pré-embriões e a média de blastocistos expandidos/mäe, näo diferiram entre tratados e controles. CONCLUSÇO: A oxcarbazepina administrada em ratas, seguindo o esquema terapêutico mencionado, näo apresentou efeito tóxico sobre a mäe e näo alterou o desenvolvimento do pré-embriäo

Drogadicción embriofetal por abuso de pasta base de cocaína durante el embarazo / Fetal drug addiction as a consequence of maternal cocaine base paste abuse during pregnancy

Background: Fetal drug addiction is a serious public health problem. In the United States 10 to 15 percent of children have been exposed "in utero" to cocaine. In a Chilean public health service, more than 200 offspring of cocaine free base abuser have been detected. Aim: To analyze the clinical and social features of 100 children exposed to cocaine free base during fetal development. Patients and methods: Clinical features of children born from cocaine free base consume mothers were described at birth. During subsequent follow up, growth and development, disease episodes, developmental alterations and social situation were recorded. Data was compared with other newborns from the same health service. Results: Compared to their normal counterparts, exposed children has a lower birth weight, the frequency of premature babies was thrice higher, and small-for-gestational age children were four times more common. There was also a higher prevalence of cardiac malformations, seizures and apnea. Hospital admissions were more frequent, prolonged and required more complex facilities. During follow up, undernutrition and stunting were more prevalent. Psychomotor retardation was present in 67 percent of children and behavioral disturbances in 93 percent. Most of these children are governmental protection. Conclusions: Strategies to prevent drug abuse during pregnancy and its devastating medical and social consequences should be urgently developed

effect of gibberellic acid on fresh, processed pear and consuming impact hazards

Gibberellic acid [GA3] is the most widely used growth regulator for increasing the yield of Le-Conte pears. Twenty ppm of GA3 were sprayed three times on pear trees during the growing period. The effects of GA3 on the physical and chemical properties of fresh Le-Conte pears were studied. Also, its effects on some chemical characteristics of syrup and quarters of canned pears were determined. The residuals of GA3 in treated fresh and processed Le-Conte pears were 18.41 and 8.75 ppm, respectively, by using gas liquid chromatography. However, no residuals were detected in control fresh and canned pears. The effects of gibberellic acid embryotoxicity and morphological malformation were determined by using fertile eggs which were injected with 0, 5, 20, 60 and 200 ppm concentration of GA3. During the incubation period, the lowest concentration of GA3 [5 ppm] caused relatively the highest reduction in egg weight and vice versa. At the end of incubation period, the numbers of hatching eggs of total ten for each concentration were 10, 7, 5, 3, 2 for the treatments 0, 5, 20, 60 and 200 ppm of GA3, respectively. These results revealed that the high concentrations of GA3 were more toxic on embryos compared with control