Ethanol teratogenicity involving the developing brain is the leading preventable cause of mental deficiency in the Western world. Chronic prenatal ethanol exposure (CPEE) may be a risk factor for ethanol abuse and altered responsiveness to nicotine in postnatal life. Previous studies in our laboratory have utilized maternal oral administration of a high-dose (4 g ethanol/kg maternal body weight/day) ethanol regimen that induces structural and functional deficits in the fetus and postnatal offspring. The objective of this thesis was to test the hypotheses that moderate CPEE produces in postnatal offspring: (i) structural and functional teratogenic effects; (ii) increased ethanol preference; (iii) altered responsiveness to acute nicotine; and (iv) increased nicotinic acetylcholine receptors (nAChR) in forebrain structures, namely the hippocampus and frontal cortex. Pregnant Dunkin-Hartley-strain guinea pigs were given 24-h access to aqueous ethanol solution (5%, v/v) sweetened with sucralose (1g/L) or aqueous sucralose solution (1g/L) throughout gestation. Spontaneous locomotor activity in an open field was measured in offspring on postnatal day (PD) 10. Beginning around PD 40, ethanol preference in the offspring was determined using a two-bottle-choice paradigm. Each animal was given 2-h daily access to aqueous ethanol solution (0 - 3%, v/v) and water over 33 days of testing. Subsequently, hippocampal and frontal cortical tissues were obtained for the measurement of nAChR population by radioligand binding. Moderate maternal consumption of the aqueous ethanol produced growth restriction in postnatal offspring of both sexes, and increased spontaneous locomotor activity in male offspring only. These postnatal outcomes are similar to the teratogenic effects produced by a high-dose, binge-type ethanol regimen. Compared with control, offspring from mothers that consumed ethanol throughout gestation exhibited greater preference for aqueous ethanol, and a decrease in the concentration of nAChRs in the frontal cortex, but not the hippocampus. These data demonstrate that, in the guinea pig, moderate maternal consumption of ethanol is a useful model for studying ethanol neurobehavioural teratogenicity; and chronic prenatal exposure to ethanol enhances ethanol preference in young adult offspring and altered expression of nAChRs in the frontal cortex. / Thesis (Master, Pharmacology & Toxicology) -- Queen's University, 2009-06-19 10:26:40.229

Maternal ethanol consumption during pregnancy can produce teratogenic outcomes in offspring, which are collectively termed Fetal Alcohol Spectrum Disorder (FASD). Central nervous system (CNS) dysfunction is a debilitating and permanent manifestation of FASD. Recent studies indicate that chronic prenatal ethanol exposure (CPEE), via maternal ethanol administration, also impairs metabolic function in offspring. The mechanism of ethanol teratogenicity is multi-faceted and could involve alterations in insulin and insulin-like growth factor (IGF) signaling pathways. These pathways are not only important for metabolism, but are also involved in CNS neuronal survival and plasticity, which are impaired by CPEE. The overall goal of this thesis research was to study, in the guinea pig, neurobehavioural and metabolic effects of CPEE and to investigate whether these effects were associated with altered CNS and peripheral insulin/IGF signaling pathways. In postnatal offspring, CPEE decreased brain weight and altered performance of the modified Biel-maze task, which was a sensitive measure of apparent cognitive dysfunction and executive function deficits. Furthermore, CPEE produced various manifestations of metabolic teratogenicity in offspring, including decreased birth weight, postnatal catch-up body growth, increased whole-body adiposity, disrupted pancreatic morphology, dysregulation of blood glucose concentration and increased liver weight in adulthood. The CPEE-induced neurobehavioural and metabolic effects were associated with alterations of the insulin/IGF signaling pathways in the CNS and periphery. In the liver, CPEE decreased mRNA expression of IGF-1, IGF-1 receptor, and IGF-2 in male and female offspring, and increased mRNA expression of insulin receptor substrate (IRS)-2 in male offspring only compared with nutritional control. Female CPEE offspring had decreased hepatic mRNA expression of insulin receptor compared with male CPEE offspring. In the prefrontal cortex, IRS-2 mRNA expression was increased in male and female CPEE offspring compared with nutritional control. The studies of this thesis have contributed to the understanding of the neurobehavioural and metabolic consequences of CPEE in offspring, which are associated with impairment of the insulin/IGF signaling pathways. / Thesis (Ph.D, Pharmacology & Toxicology) -- Queen's University, 2014-04-25 10:52:50.048

No description available.

Thesis (M.S.)--University of Delaware, 2007. / Principal faculty advisor: William W. Saylor, Dept. of Animal and Food Sciences. Includes bibliographical references.

nÃo hà / Em decorrÃncia de novos conhecimentos sobre seu mecanismo de aÃÃo e propriedades farmacolÃgicas, a talidomida tem sido utilizada por um nÃmero cada vez maior de profissionais, para condiÃÃes clÃnicas as mais diversas. Devido ao alto potencial teratogÃnico, seu uso seguro e racional requer um acompanhamento por rigoroso programa de FarmacovigilÃncia. Este estudo teve como objetivo avaliar o percurso terapÃutico da prescriÃÃo à utilizaÃÃo da talidomida em Ãrea urbana no Nordeste do Brasil. Foram utilizados dados dos arquivos de receitas de um Centro de Referencia para HansenÃase do MinistÃrio da SaÃde e informaÃÃes obtidas atravÃs da aplicaÃÃo de questionÃrios semi-estruturados a 94 usuÃrios e 20 mÃdicos prescritores de talidomida, no perÃodo de 1 de janeiro de 2005 a 31 de julho de 2006. A maioria dos usuÃrios (70%) era do sexo masculino, com idade entre 41 e 65 anos (40,7%) e a principal indicaÃÃo foi o Eritema Nodoso HansÃnico (70%), sendo 29,4% das receitas prescritas por dermatologistas. Entre as mulheres entrevistadas, mais da metade estava em idade fÃrtil, 85% utilizam mÃtodo contraceptivo, sendo a laqueadura tubÃria em 47%. O risco de teratogenicidade à alertado ao paciente por 85% dos prescritores. O medicamento foi considerado eficaz para 70,9% dos usuÃrios entrevistados e a sonolÃncia foi referida como efeito adverso para 80% deles. Conclui-se que a talidomida à utilizada principalmente para as indicaÃÃes oficiais do MinistÃrio da SaÃde, entretanto à evidente a ampliaÃÃo do seu uso clÃnico para numerosas condiÃÃes off label, com eficÃcia considerÃvel e efeitos adversos leves a moderados. Apesar dos prescritores preocuparem-se com a anticoncepÃÃo durante e apÃs o tratamento, quando a talidomida à utilizada em mulheres com risco de gravidez; as determinaÃÃes da ANVISA quanto à prescriÃÃo e ao uso da talidomida nÃo vÃm sendo adequadamente seguidas, observando-se que os usuÃrios sÃo pouco informados quanto aos efeitos adversos do medicamento, tornando premente a necessidade da regulamentaÃÃo da Lei 10.651, dentro da nova realidade de utilizaÃÃo da talidomida, tornando seu uso clÃnico racional e controlado. / In result of new knowledge on its mechanism of action and pharmacological properties, thalidomide has been used for a number each bigger of professionals, for most diverse clinical conditions. Because of its high teratogenical potential, its safe and rational use requires an accompaniment for rigorous program of pharmacovigilance. The objective of this study was to evaluate the therapeutical prescription and the use of thalidomide in north-eastern urban area of Brazil. The data were gotten from the prescription archives of a Center of Reference for Leprosy of the Health Department and information gotten through the application of half-structuralized questionnaires the 94 users and 20 medical prescritores of thalidomide, during the period of January 2005 to July 2006. The majority of the users (70%) were men, with age between 41 and 65 years (40.7%), the main indication was the Erythema Nodosum Leprosum (70%), and 29.4% of prescriptions were prescribed for dermatologists. Between the interviewed women, more than the half were in fertile age, 85% use contraceptive method, it being the tubal ligation in 47%. Teratogenicity risk is alerted to the patient by 85% of the prescritores. The medicine was considered efficient for 70.9% of the interviewed users and the sleepiness was related as adverse effect for 80% of them. It is concluded that thalidomide is used mainly for the official indications of the Health Department, however is evident the magnifying of its clinical use for numerous conditions off label, with considerable effectiveness and light or moderate adverse effects. Although the prescritores were worried about the contraception during the treatment, when thalidomide is used in women with pregnancy risk; the determination of the ANVISA about prescription and use of thalidomide has not being adequately followed, observing that the users are inadequately informed about the adverse effect of the medicine. Itâs urgent the necessity of the regulation of Law 10,651, inside of the new reality of use of thalidomide, in order to its rational and controlled clinical use.

La règlementation européenne requiert l’évaluation de la reprotoxicité des ingrédients cosmétiques sans avoir recours aux tests sur les organismes définis par la directive européenne sur les animaux utilisés à des fins scientifiques. Pour cribler par exclusion des substances chimiques, l’industrie cosmétique a besoin de développer une méthode alternative à l’expérimentation animale prédictive et spécifique à l’identification d’agents tératogènes (substances entraînant au cours du développement embryonnaire et de manière définitive des malformations physiques et/ou fonctionnelles). Pour cela, le poisson zèbre, le poisson médaka et l’amphibien xénope aux stades embryonnaires ont été évalués sur une liste de 43 substances de référence. Le médaka a été sélectionné pour la fiabilité de son approvisionnement, la robustesse de ses stades embryonnaires lors des manipulations, ainsi que pour les performances du test l’utilisant. De plus, ce test permet de détecter les agents tératogènes les plus puissants, près de la moitié des 26 substances tératogènes de notre liste. Son taux de spécificité est fixé à 100% pour identifier correctement les 17 substances négatives dont l’absence d’effets tératogènes chez l’homme ou un organisme modèle mammifère, est avérée. Néanmoins, les performances de ce test pourraient être améliorées par son automatisation et par l’intégration de la quantification de nouveaux paramètres pour l’identification de malformations fonctionnelles. Enfin, pour prédire l’innocuité d’une substance chimique chez l’Homme, le test prédictif de tératogénicité utilisant les embryons de médaka doit être intégré dans une stratégie globale d’évaluation de la tératogénicité. / European legislation requires the assessment of reproductive toxicity of cosmetic ingredients without using tests on the organisms defined by the European directive on animals used for scientific purposes. To screen by excluding chemicals, cosmetics industry needs to develop an alternative method to animal testing, which needs to be predictive and specific in identifying teratogen agents (during embryonic development substances causing definitive physical and / or functional defects). For this, zebrafish, medaka fish and Xenopus amphibian at embryonic stages were assessed on a list of 43 reference substances. Medaka has been selected to the reliability of its supply, the robustness of its embryonic stages during handling, as well as for performance of its test. In addition, this test can detect the most potent teratogen agents, nearly half of the 26 teratogens of our list. Its specificity rate is set at 100% for correctly identifying 17 negative substances for which the absence of teratogenic effects is proved in humans or mammalian model organism. However, the performance of this test may be improved by its automation and integration of new quantification parameters for the identification of functional defects. Finally, to predict the safety of a chemical in humans, the predictive teratogenicity test using medaka embryos must be integrated into a comprehensive strategy for assessing the teratogenicity.

FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / INTRODUÃÃO: O misoprostol (CytotecÂ) à um anÃlogo de prostaglandina E1, inicialmente comercializado com finalidades terapÃuticas do trato gastrintestinal, de uso proscrito em gestantes pelo risco de abortamento. A realidade do aborto e o ineficiente controle de medicamentos em nosso paÃs tornaram generalizado seu uso como mÃtodo abortivo. Estudos demonstram que o potencial abortivo do misoprostol à variÃvel e seu uso sem acompanhamento mÃdico pode levar a uma gestaÃÃo que nÃo se perde, gerando risco para o embriÃo/feto. VÃrios relatos de casos e estudos epidemiolÃgicos associam o uso de misoprostol durante a gestaÃÃo com crianÃas malformadas, especialmente seqÃÃncia de MÃebius, defeitos de reduÃÃo de membros e diversas anomalias do sistema nervoso central. O risco do surgimento destes defeitos nÃo pÃde ainda ser determinado com os dados atualmente disponÃveis, fazendo-se necessÃrio a continuidade de pesquisas. OBJETIVOS: Identificar em recÃm nascidos (RNs) malformados nas principais maternidades de Fortaleza e em controles normais a freqÃÃncia de exposiÃÃo ao misoprostol e apresentar o espectro de MFs dos neonatos expostos. MÃTODOS: Estudo de caso controle, com busca ativa diÃria de RNs malformados e controles pareados em quatro maternidades pÃblicas de Fortaleza â CE, no perÃodo de julho a novembro de 2005, para entrevista com a parturiente utilizando questionÃrio estruturado, na busca por exposiÃÃes diversas durante a gestaÃÃo, inclusive ao misoprostol. RESULTADOS: Os grupos eram homogÃneos quanto ao perfil sÃcio-demogrÃfico e principais caracterÃsticas, apresentando diferenÃas somente em desfechos desfavorÃveis mais esperados em RNs MFs, como menor peso (p=0,0001), menor adequaÃÃo peso x idade gestacional (p=0,006), maior natimortalidade (p=0,024) e maior mortalidade perinatal (p=0,0001). Ambos os grupos tiveram Ãndice de assistÃncia prÃ-natal no mÃnimo adequada (69%), diferindo somente na quantidade de ultra-sonografias (US) realizadas a mais pelos casos (p=0,003). Quanto aos fatores de risco, a Ãnica diferenÃa consistiu no grupo caso ter apresentado maior freqÃÃncia em apresentaÃÃo pÃlvica (19,8%, p=0,037). Aproximadamente 84% das mÃes relataram exposiÃÃo a pelo menos um medicamento durante a gestaÃÃo, e a mÃdia de medicamentos consumidos por gestante foi de 3,72. O uso de fumo, Ãlcool e drogas ilÃcitas foi pouco reportado, e somente o fumo apresentou-se mais freqÃente no grupo controle (p=0,0171). A maior parte das gestaÃÃes foi declarada como planejada ou desejada (70% do total). O relato de tentativa de aborto foi de 6,8% do total da amostra, havendo maior citaÃÃo de uso de misoprostol no grupo caso, embora nÃo tenha sido estatisticamente significativo. CONCLUSÃO: Os achados deste estudo sugerem que ocorre uma maior exposiÃÃo de misoprostol durante a gestaÃÃo em RNs malformados comparados a RNs saudÃveis, Odds Ratio (OR) = 3,65 [IC95%: 0,74;17,91]. O espectro de MFs encontradas, associadas ao misoprostol foi: hidrocefalia, mielomeningocele, agenesia de quadril, pà equinovaro, luxaÃÃo de joelho, luxaÃÃo de quadril, agenesia de falanges distais, sindactilia, polidactilia, imperfuraÃÃo anal, ausÃncia de testÃculos no bolso escrotal e higroma cÃstico. / INTRODUCTION: Misoprostol (CytotecÂ) is a prostaglandin E1 analog, previously commercialized with therapeutic purposes, with proscribed use in the gravid due to the risk of miscarriage. The common practice of abortion and the inefficient control on access to drugs in our country has lead to the generalized use of this drug as an abortive method. Studies have shown that the abortive potency of misoprostol is variable and its use without medical assistance may lead to thriving gestation, and a consequent risk of malformation to the fetus. Various case reports and epidemiological studies associate the use of misoprostol during gestation with offspring bearing malformations, especially with the MÃebius sequence, terminal transverse-limb defects and diverse other anomalies of the central nervous system. The risk of acquiring these malformations cannot however be determined with available data, thus, there is a need for continuous research. OBJECTIVE: Identifying newborns bearing malformations in the leading maternities in Fortaleza and selecting their respective study controls, determining the frequency of exposition to misoprostol and identifying the spectrum of anomalies in the exposed group. METHODS: A case control-study, with a daily active search within the four largest maternities in Fortaleza, Ceara for newborn with congenital defects and a paired control, from July to November 2005. Every mother was interviewed with a questionnaire in the search for diverse expositions during pregnancy, including misoprostol. RESULTS: The groups were homogenous in respect to their socioeconomic profile and other main characteristics. Differences were found in respect to unfavorable outcomes among newborn with congenital defects like low weight (p=0,0001), low weight in relation to gestational age (p=0,006), increased natimortality (p=0,024) and increased perinatal mortality (p=0,0001). Both groups had adequate pre-natal assistance (69%), deferring only in the amount of ultrasonographic exams carried out in the case group (p=0,003). In regards to risk factors, the only deference encountered was the case group having more breech presentation (19,8%, p=0,037). Approximately 84% of mothers had been exposed to at least one medication during gestation, and the average number of drugs consumed was 3, 72. The use of tobacco, alcohol and illicit drugs was rarely informed, and only tobacco smoking was more frequent in the control group (p=0,0171). Most gestation were reported as planed or desired (70% of the total). Attempted abortion was reported in 6,8% of whole sample, with the use of misoprostol in the case group, although without statistic significance. CONCLUSION: The findings of these study suggest that exposition to misoprostol during gestation occurs more frequently in newborn with congenital defects compared with healthy ones, Odds Ratio (OR) = 3,65 [IC95%: 0,74;17,91]. The spectrum of malformations found and associated with misoprostol was hydrocephalus, meningomyelocele, agenesis of hip, equinovarus, luxation of the knee, hip congenital dislocation, absence of distal phalanges, syndactyly, polidactyly, anal imperforation, criptorchidism and cystic higroma.

The anticonvulsant drug, Dilantin, in many cases must be taken by epileptic mothers to control seizures during pregnancy, but unfortunately, it has been characterized as a human teratogen. It has also been demonstrated that many of the teratogenic effects of Dilantin occur during postimplantation, but some studies implicate a detrimental role for Dilantin during the preimplantation stages of development. Some of the postimplantation effects include congenital malformations and the potential'loss of the fetus. Our lab has proposed that in preimplantation mouse embryos the drug may be altering the timing of expression of cell cycle regulatory proteins and therefore, we have begun to examine the expression of these proteins. Thus, it was the goal of this study to characterize and localize various cell cycle proteins at specific time points in normal in vivo preimplantation mouse embryos, as this will provide important baseline information for studies on how anticonvulsant drugs may alter cell cycle regulation in embryos.Western blotting has confirmed the presence of cyclin BI in G1 of the first cell cycle. Both cyclin E and CDK2 were not detected in GI or G2/M of the first cell cycle or GI of the second cell cycle.From the immunogold TEM experiments, the density of cyclin B1 staining was observed to be the highest at G1 of the first cell cycle and declined at S and G2/M. Cyclin B 1 was detected in all regions of the embryo including the microvilli, cortical cytoplasm, interior cytoplasm, and was observed to be associated with vesicles and some filaments. The gold particles at GI, S, and G2/N4 of the first cell cycle and G1 of the second cell cycle appear to be associated with filamentous and membraneous structures and not free in the cytoplasmic spaces. Cyclin B 1 expression was more concentrated around vesicles at G1 of the first cell cycle and in general, was more concentrated around vesicles than in microvilli and cortical cytoplasm, interior cytoplasm, or around filaments at each cell cycle stage tested. / Department of Biology

A Organização Mundial da Saúde revela que mais de 20 milhões de crianças nascem com baixo peso ao nascimento em todo o mundo, sendo a má nutrição o principal fator desencadeante. Estudos realizados nas duas últimas décadas mostram que o status nutricional materno pode ser crítico no desenvolvimento de teratogenicidade; porém não há trabalhos que comprovem a associação entre restrição alimentar materna e a ocorrência de malformações. No entanto, o conceito de teratogênese não se restringe apenas às malformações estruturais logo após o nascimento, também são consideradas alterações funcionais, como aquelas comportamentais ou no sistema imune, entre outras, que podem se manifestar somente na maturação pós-natal. Assim, o presente trabalho visou verificar os efeitos da restrição alimentar materna durante a gestação, avaliando-a por meio tanto do protocolo clássico de teratogenicidade, como através de protocolos de imunoteratologia, analisando-se neste caso, as possíveis alterações no sistema imune da prole após o desmame e também na idade adulta. Foram empregadas ratas Wistar prenhes, divididas em cinco grupos iguais, um controle (CO) no qual os animais receberam ração ad libitum, e nos demais grupos, as fêmeas foram submetidas à restrição alimentar, do 6º ao 17º dia de gestação, diminuindo-se em 15 (E15), 40 (E40), 55 (E55) e 70% (E70) da quantidade de ração consumida pelos animais do grupo CO. Por meio do protocolo clássico de teratogenicidade, verificaram-se as possíveis alterações ósseas e viscerais sobre a prole. Empregou-se ainda o protocolo de imunoteratologia, no qual foram realizados testes nas proles tanto ao desmame como na idade adulta, e aferiu-se os seguintes parâmetros: hemograma, peso relativo do timo e do baço, celularidade do baço e da medula óssea; a imunidade inata: atividade de macrófagos peritoneais por meio da fagocitose, produção de peróxido de hidrogênio e óxido nítrico; a imunidade humoral: produção de anticorpos pelo ensaio do plaque forming cell e a titulação de anticorpos anti-eritrócitos de carneiro; e a imunidade celular: avaliação da hipersensibilidade tardia. Em relação às avaliações teratogênicas clássicas, estas mostraram haver, naqueles filhotes provenientes das ratas submetidas às restrições alimentares (E40, E55 e E70), diminuição no peso ao nascimento, aumento da proporção de fetos mortos até uma hora após o nascimento e aumento do número de fetos com ureter sinuoso; no entanto, não foi constatada a ocorrência de malformações graves, que pudessem colocar em risco a vida do concepto. Já as avaliações pós-natais revelaram diminuição no ganho de peso, do nascimento até a idade adulta, das proles provenientes das ratas do grupo E70. Em relação às alterações imunoteratogênicas, houve aumento no peso relativo do timo e da resposta imune celular nas proles destas mães submetidas à maior restrição alimentar, quando estes animais foram avaliados aos 21 dias de idade. Quando realizou-se este estudo nas proles com 70 dias (idade adulta), os filhotes provenientes de mães das diferentes restrições alimentares apresentaram aumento da resposta imune humoral; além disto aqueles filhotes de mães E70, mostraram aumento da resposta imune celular. Os dados apresentados na presente pesquisa permitem sugerir que a restrição alimentar em ratas Wistar durante a organogênese fetal, embora não promova malformações estruturais, produz prole de menor peso ao nascimento e é capaz de gerar alterações significantes no sistema imune dos filhotes. / The World Health Organization has reported that more than 20 million children worldwide are born with low birth weight, with malnutrition the main triggering factor. Studies in the past two decades have shown that maternal nutritional status may be critical in the development of teratogenicity, but there are no studies that directly relate maternal feed restriction and malformation. However, teratogenecity is not restricted only to structural abnormalities at birth, but may also include functional changes, such as behavioral or immune system alterations, among others, which may manifest themselves only in the postnatal period of maturation. Thus, this work aimed to assess the effects of maternal food restriction in pregnant rats using classical and immunoteratogenic protocols to evaluate the offspring. Thus, possible immune system changes were evaluated in the offspring after weaning and after maturation. Pregnant females were divided into five groups, a control group (CO) in which the animals received feed ad libitum, and four other groups, in which females were fed a restricted amount based on the total ingested by controls: 15% (E15), 40% (E40), 55% (E55) and 70% (E70) during days 6 to 17 of gestation. Rats were humanely euthanized and teratogenicity was evaluated using skeletal and visceral measurements. Immunoteratogenic effects were determined in weaned and mature offspring (10 weeks) using blood, thymus and spleen relative weights and spleen and bone marrow cellularity. In addition, innate immunity was determined using activity of peritoneal macrophages through phagocytosis, and production of hydrogen peroxide and nitric oxide. Humoral immunity was determined using production of antibodies by the plaque-forming cell assay and titers of anti-sheep red blood cells. Cellular immunity was determined by evaluating delayed type hypersensitivity. Traditional teratogenic indices showed that pups from females subjected to feed restriction (E40, E55 and E70) had a decrease in birth weight, an increased proportion of dead fetuses up to one hour after birth, and an increase in the number of fetuses with kinked ureter. No major malformations serious enough to threaten the life of the conceptus were observed. There was a postnatal decrease in weight gain in offspring from mothers of group E70 from birth to adulthood. There was also immune system changes, with an increase in the thymus relative weight (E40, E55, E70) and cellular immune response in offspring (21 days of age). When offspring were evaluated after maturation, those pups from mothers with feed restriction had increased humoral immune responses; in addition offspring from the E70 group showed an increase in cellular immune response. The data presented in this study suggest that feed restriction in Wistar rats during organogenesis does not promote structural malformations, but instead results in offspring with lower birth weights, and also promoted significant changes in the immune system of rat pups.

Nos dias atuais, a utilização de fitoterápicos tem crescido acentuadamente. No Brasil, um país cuja flora nativa é riquíssima, tem-se investido substancialmente em pesquisas nesta área. Isto se deve, em parte, à necessidade de novos medicamentos, ao interesse na comercialização destes produtos, ao interesse na preservação da cultura popular e da reserva da flora nacional. Paralelamente a este cenário, está a crença de que medicamentos fitoterápicos são inofensivos em circunstâncias especiais tais como: gravidez, hipertensão, diabetes, etc. É como se os fitoterápicos atuassem especificamente sobre uma determinada patologia não sobre o metabolismo como um todo. A Mikania glomerata Sprengel, conhecida popularmente como guaco e originária da América do Sul, é uma planta subarbustiva, que nasce nas matas e cerrados e, que se adapta muito bem ao cultivo doméstico. Ela é vastamente utilizada pela população no tratamento de doenças como a asma, bronquite, e reumatismo, além de possuir efeito antifúngico, antimicrobiano, antialérgico, antiinflamatório e antiofídico, na grande maioria das vezes administrada sem supervisão de profissionais da área da saúde. Neste estudo, nosso objetivo é estudar a possível ação do extrato vegetal de Mikania glomerata Sprengel (guaco) no perfil reprodutivo e gestacional de camundongos (Mus musculus domesticus) e determinar se a administração desta droga pode comprometer o embrião/feto e placenta durante a prenhez. Este estudo mostrou que a utilização do extrato de Mikania glomerata em doses supra-terapêuticas pode atuar sobre processos morfofuncionais orgânicos, interferindo no crescimento placentário e fetal e podendo levar ao insucesso gestacional e ao aparecimento de defeitos congênitos. Além disto, a diminuição do crescimento fetal observado nas doses consideradas terapêuticas também é um alerta para o uso inadvertido do extrato de guaco sem acompanhamento médico devido, em qualquer período gestacional. / Nowadays, the use of medicinal plants has grown dramatically. In Brazil, a country whose native flora is rich, has invested substantially in research in this area. This is due in part to the need for new drugs, the interest in marketing these products, the interest in the preservation of popular culture and the reserve of national flora. In parallel with this scenario is the belief that phitotherapeutics are harmless in special circumstances such as pregnancy, hypertension, diabetes, etc. It is as if the herbal acted specifically in a determinate disease not on the metabolism as a whole. The Mikania glomerata Sprengel, popularly known as guaco and originating from South America, is a plant undergrowth, which rises in the forests and savannahs, and that lends itself very well to domestic cultivation. It is widely used by local people in the treatment of diseases such as asthma, bronchitis, and rheumatism, as well as having antifungal effect, antimicrobial, antiallergic, anti-inflammatory and anti-snakebite, in most cases administered without the supervision of health professionals. In this study, our goal is to study the possible action of plant extract of Mikania glomerata Sprengel (guaco) in pregnancy and reproductive profile of mice (Mus musculus domesticus) and determine whether the administration of this drug may affect the embryo / fetus and placenta during pregnancy . This study showed that the use of extract of Mikania glomerata at supratherapeutic doses can act on morphofunctional organic processes, interfering with fetal and placental growth and could lead to pregnancy failure as well as contribute to the appearance of birth defects. Furthermore, the decrease in fetal growth observed in therapeutic doses is also considered a warning to the inadvertent use of the extract guaco without medical supervision because, at any gestational period.