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.

Does Enoxaparin treatment have any effects on the placenta in women with unexplained histories of habitual abortion? A case control study

ABSTRACT BACKGROUND: It is very common to offer low molecular weight heparin (LMWH) medications to women with unexplained habitual abortion, to increase the livebirth rate. Although no benefit from LMWH has been clearly demonstrated, examination of the effects of enoxaparin on placental structure is lacking. OBJECTIVE: To assess placental structural changes in pregnancies treated with enoxaparin, compared with controls. DESIGN AND SETTING: Case-control study in an obstetrics and gynecology unit of a tertiary-level university hospital in Turkey. METHODS: Forty patients who had had term pregnancies and live births but also histories of habitual abortion were recruited for this study. Placentas were sampled using a systematic random sampling method. Tissue samples were obtained, embedded and sectioned for routine histological analyses. Hematoxylin and eosin staining was used. Surface area and length estimates from placental components were evaluated by using Image J. Cell proliferation and apoptosis were also assessed via immunohistochemistry. RESULTS: There were no significant differences between the groups regarding maternal age, abortion rate, birth weight or gestational age. Comparison of the enoxaparin and control groups showed that there were no significant differences in terms of surface area and ratios of placental components. We found that Bcl-2 was generally expressed at high levels in the enoxaparin group, while there was no difference in terms of Ki-67 between the groups. CONCLUSIONS: This study demonstrates that enoxaparin did not show any significant effect on the placental structure of cases that had histories of habitual abortion.

Evaluation of placental epigenetic changes due to morphine consumption / Evaluación de cambios epigenéticos de la placenta por consumo de morfina

Based on previous studies, a variety of bioenvironmental elements including inappropriate nutrition, diseases, infections, stressors, and medications are involved in epigenetic changes. Drug abuse is one of the most important causes of epigenetic changes and a concern in today's world. Studies have shown that morphine use by pregnant mothers causes several disorders in mothers in addition to transferring abnormalities to the next generation (placenta and embryo). Epigenetic factors such as morphine cause changes in gene expression in placenta as the first embryonic defense barrier. Because placenta does all the nutritional exchanges between mother's and embryo's blood, placental health guarantees normal embryonic development. Many studies have been conducted on defects caused by epigenetic factors including medication use. Opioid abuse including morphine abuse has endangered health of many people. Morphine changes gene expression by binding to opioid receptors on placental villi. Based on the studies, major epigenetic changes due to drug use are mediated by DNA methylation and histone changes. Recognizing different epigenetic factors and their effect on placental and embryonic development is among modern studies. The importance of recognizing epigenetic changes caused by drug abuse by pregnant mothers can be the most important way to prevent adulthood diseases in the embryo and in some cases miscarriage. Changes induced by epigenetic factors can be moderated or reversed by controlling the epigenetic factors. This study is a review of changes caused by morphine use by pregnant rats on development of placenta.

Basado en estudios anteriores, una variedad de elementos bioambientales incluyendo la nutrición inadecuada, enfermedades, infecciones, factores de estrés, y los medicamentos están involucrados en los cambios epigenéticos. El abuso de drogas es una de las causas más importantes de los cambios epigenéticos y una preocupación en el mundo actual. Los estudios han demostrado que el uso de la morfina por parte de las madres embarazadas es la causa de varios trastornos en las madres, además de la transferencia de anormalidades a la siguiente generación (la placenta y el embrión). Factores epigenéticos como la morfina causan cambios en la expresión génica en la placenta como la primera barrera de defensa embrionaria. Debido a que la placenta es el medio de todos los intercambios nutricionales entre la madre y la sangre del embrión, la salud de la placenta garantiza el desarrollo embrionario normal. Muchos estudios se han realizado sobre los defectos causados por factores epigenéticos que incluyen el uso de medicamentos. El abuso de opioides, incluyendo la morfina ha puesto en peligro la salud de muchas personas. La morfina produce cambios de expresión génica mediante la unión a los receptores opioides en vellosidades placentarias. Basado en los estudios, los principales cambios epigenéticos debido al consumo de drogas están mediadas por metilación del ADN y los cambios en las histonas. En la actualidad se han publicado estudios referente al conocimiento de diferentes factores epigenéticos y su efecto sobre la placenta y el desarrollo embrionario. La importancia de reconocer los cambios epigenéticos causados por el abuso de drogas por mujeres embarazadas puede ser la forma más importante para prevenir las enfermedades de la edad adulta en el embrión y en algunos casos del aborto espontáneo. Los cambios inducidos por factores epigenéticos pueden ser moderados o revertidos mediante el control de los factores epigenéticos. Este estudio es una revisión de los cambios en el desarrollo de la placenta causados por el uso de morfina en ratas preñadas.

Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats

PURPOSE: To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. METHODS: Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A p<0.05 was considered statistically significant. RESULTS: We did not observe statistically significant differences between groups when comparing the average weight of the foetuses and placentas, rate of female VS males, rates of pre-implantation loss (RPL), rates of efficiency implantation (REI), rates of post-implantation loss (RPIL) and rates of foetal viability (RFV). CONCLUSIONS: There was no significant effect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats. .

Morphological alterations in mouse placenta induced by diazepam / Alteraciones morfológicas inducidas en la placenta de ratón por diazepam

Diazepam (DZ) is a benzodiazepine that belongs to the group of minor tranquilizers with myo-relaxing and anticonvulsant properties. DZ and its metabolites cross the placental barrier in human, monkey, hamster, and mouse, and accumulate in the placenta. Our aim was to investigate, through histological techniques, and semifine sections if DZ induces morphological changes in the placenta. Twenty female mice of the ICR strain were distributed randomly in two groups. One group (DZ) was treated from days 6 to 17 of gestation with a single daily subcutaneous (sc) dose of DZ of 2.7 mg/kg/ (bw); the second, control group (C) was treated with saline solution. All females (10 DZ and 10 C) were killed by decapitation. Placentas were extracted and fixed in phosphates-buffered 10% formaldehyde, pH 7.3, dehydrated, and embedded in paraffin to obtain 3 µm thick sections or fixed in 2.5% glutaraldehyde, post-fixed in 1% OsO4, embedded in epoxy resin. Histological sections were stained with hematoxylin-eosin or Weigert´s iron hematoxylin. Semifine sections were stained with toluidine blue. All sections were observed under comparative light microscopy. The DZ-group showed thinned placental barrier with multiple vacuoles. Nuclei of trophoblast cells (TCs) and trophoblast giant cells (TGCs) presented heterochromatin in coarse granules, atypically distributed in the karyolymph and conspicuous nucleoli. The cytoplasm of the TGCs was vacuolated and chromatin had a similar appearance to that observed in TCs. The total area of the placental barrier was measured in µm2/µm2; the area in the DZ group was reduced as compared with the C group (P<0.001). Alterations of TGCs could be due to an interaction of DZ with peripheral type benzodiazepine receptors involved in progesterone biosynthesis. Administration of DZ in mice alters the placental barrier and TGCs which could affect their physiology and causes teratogenic effects on the ovary and testis involved in steroid hormones biosynthesis.

El diazepam (DZ) es una benzodiazepina que forma parte de los tranquilizantes menores con propiedades miorrelajantes y anticonvulsivantes. El DZ y sus metabolitos atraviesan la barrera placentaria en el humano, mono, hámster y ratón, y se acumula en ésta. Nuestro propósito fue investigar a través de técnicas histológicas y en cortes semifinos si el DZ induce cambios morfológicos en la placenta de ratón. Hembras de ratón de la cepa ICR se distribuyeron al azar en dos grupos. Un grupo (DZ) fue tratado del día 6 al 17 de la gestación con dosis únicas diarias subcutáneas (sc) de DZ de 2.7 mg/kg (pc); el segundo grupo control (C) se trató con solución salina. Todas las hembras (10 DZ y 10 C), se sacrificaron por decapitación. Se extrajeron las placentas y se fijaron en formaldehido al 10% amortiguado con fosfatos pH 7.3, se deshidrataron y se incluyeron en parafina para obtener cortes de 3 µm, o se fijaron en glutaraldehido al 2.5%, se posfijaron en OsO4 al 1% y se embebieron en resina epóxica. Los cortes histológicos se tiñeron con hematoxilina-eosina o con hematoxilina férrica de Weigert. Los cortes semifinos se tiñeron con azul de toluidina. Todos los cortes se observaron en un microscopio óptico de comparación. El grupo DZ presentó en la barrera placentaria múltiples vacuolas. Los núcleos de las células del trofoblasto y las células trofoblásticas gigantes (TGCs) presentaron heterocromatina en grumos gruesos, distribuidos atípicamente en la cariolinfa y nucléolos conspicuos. El citoplasma de las TGCs estaba vacuolizado y la cromatina tenía una apariencia similar a la observada en las células trofoblásticas. El área total de la barrera placentaria se midió en µm2/mm2; el área en el grupo DZ era reducida en comparación del grupo C (P<0.001). Las alteraciones de las células trofoblásticas y de las TGCs podrían deberse a la interacción del DZ con los receptores benzodiazepínicos de tipo periférico involucrados en la biosíntesis de progesterona. La administración de DZ en el ratón altera la barrera placentaria y las TGCs que podrían afectar su fisiología y causar efectos teratogénicos en el ovario y el testículo involucrados en la biosíntesis de las hormonas esteroides.

Insulin stimulation of Akt/PKB phosphorylation in the placenta of preeclampsia patients / Estimulação com insulina da fosforilação da Akt/PKB em placenta de pacientes com pré-eclâmpsia

CONTEXT AND OBJECTIVE: Preeclampsia is a multi-systemic disease and one of the most frequent severe health problems during pregnancy. Binding of insulin triggers phosphorylation and activates cytoplasmic substrates such as phosphatidylinositol 3 kinase (PI3K). Phosphorylation of membrane phosphoinositide 2 (PIP2) to phosphoinositide 3 (PIP3) by PI3K starts Akt/PKB activation. Defects in phosphorylation of the insulin receptor and its substrates have an important role in insulin resistance. Studies have shown that insulin resistance is associated with preeclampsia and its pathophysiology. The aim here was to investigate insulin stimulation of the Akt/PKB pathway in the placenta, in normal and preeclampsia parturients. DESIGN AND SETTING: Cross-sectional study in a tertiary public university hospital. METHODS: Placentas were collected from 12 normal and 12 preeclampsia patients. These were stimulated and analyzed using Western blot to quantify the Akt/PKB phosphorylation. RESULTS: The insulin stimulation was confirmed through comparing the stimulated group (1.14 ± 0.10) with the non-stimulated group (0.91 ± 0.08; P < 0.001). The phosphorylation of Akt/PKB did not differ between the placenta of the normal patients (1.26 ± 0.16) and those of the preeclampsia patients (1.01 ± 0.11; P = 0.237). CONCLUSIONS: In vitro insulin stimulation of the human placenta has been well established. There was no difference in Akt/PKB phosphorylation, after stimulation with insulin, between placentas of normal and preeclampsia patients. Nevertheless, it cannot be ruled out that the Akt/PKB signaling pathway may have a role in the pathophysiology of preeclampsia, since the substrates of Akt/PKB still need to be investigated.

CONTEXTO E OBJETIVO: Pré-eclâmpsia (PE) é uma doença multissistêmica das mais frequentes e graves durante a gestação. A ligação da insulina inicia a fosforilação e ativação de substratos citoplasmáticos, tais como fosfatidil-inositol 3 quinase (PI3K). A fosforilação do fosfoinositol 2 (PIP2) da membrana em fosfoinosiltol 3 (PIP3) pela PI3K inicia a ativação da Akt/PKB. Defeitos na fosforilação do receptor de insulina e seus substratos têm papel importante na resistência à insulina. Estudos demonstraram que resistência à insulina está associada com pré-eclâmpsia e sua patofisiologia. O objetivo foi investigar a via de estimulação com insulina da Akt/PKB em placenta de parturientes normais e com pré-eclampsia. TIPO DE ESTUDO E LOCAL: Estudo do tipo transversal em um hospital universitário público de nível terciário. MÉTODOS: Vinte e quatro placentas (12 normais, 12 com PE) foram coletadas, estimuladas e analisadas por Western blot para quantificar a fosforilação da Akt/PKB. RESULTADOS: A estimulação com insulina foi confirmada comparando os grupos estimulados (1,14 ± 0,10) e não estimulados (0.91 ± 0.08; P < 0.001). A fosforilação de Akt/PKB não foi diferente na placenta de pacientes normais (1,26 ± 0,16) e com PE (1,01 ± 0,11; P = 0,237). CONCLUSÕES: A estimulação in vitro da placenta humana com insulina foi bem estabelecida. Não houve diferença na fosforilação da Akt/PKB após estimulação em placentas de pacientes normais e PE. Contudo, não é possível descartar a participação desta via de sinalização na patofisiologia da PE, uma vez que os substratos da Akt/PKB ainda precisam ser investigados.

[Effect of oral morphine consumption on lacunas development in ten day placenta pregnant wistar rats]

Previous studies indicated that morphine consumption during pregnancy could inhibit embryos development. Present study further evaluated the effects of oral morphine consumption on the placenta lacunas development in ten day pregnant Wistar rats. Female Wistar rats [W: 170-200 gr] were used in the present study. Experimental group were received morphine [0.05 mg/ml of tap water] after one night coupling with male rats for mating. On the day 10th of pregnancy, the pregnant animals were killed with chloroform and the placentas and uterus were removed surgically and fixed in 10% formalin for twenty days. The fixed placentas were processed and stained by H and E method and evaluated for their development. Thickness of layers, surface area of lacuna, as well as the number of cells in both maternal and fetal parts of the placentas was assessed by light microscopy. Our results indicated that the layer thickness of fetal portion and surface area of lacuna of the fetal and maternal portion of placenta reduced in experimental group. In addition, maternal portion layer thickness and cell number of the fetal and maternal portion of placenta increased in the experimental group. Our results showed that oral morphine consumption could inhibit natural function of placenta lacuna and fetal cell development

Effects of fluoxetine and imipramine in rat fetuses treated during a critical gestational period: a macro and microscopic study / Efeitos da fluoxetina e imipramina em fetos de ratas tratadas durante o período crítico da gestação: estudo macro e microscópico

OBJECTIVE: To evaluate morphological alterations in rat fetuses treated with fluoxetine and imipramine during the "critical" period of gestation. METHOD: Fifteen female rats were separated into three groups (n = 5) and treated with 10 mg/kg/day of test substances on the ninth, tenth and eleventh day of pregnancy: G1, fluoxetine; G2, imipramine hydrochloride; G3 (control), saline. On day 21, cesarean sections were performed to release the fetuses, whose bodies were weighed and macroscopically analyzed. The placenta was also weighed. The fetuses were then fixed and their encephala removed and weighed. Sections of the frontal lobe were taken for histological neuron counting. RESULTS: G1 and G2 showed the highest fetal body weight. Placental weight showed statistical differences (p < 0.01): G1 weighed more than G2 and G3. Otherwise, G2 exhibited the highest encephalon weight, statistically differing from G3 (control) and fluoxetine-treated G1 (p < 0.01). However, G1 did not statistically (p > 0.01) differ from the control group. G3 showed the highest number of neurons per area when compared to G1 and G2 (p < 0.01). CONCLUSION: The use of antidepressants in rats caused an increase in fetal weight and a decrease in the number of fetal frontal lobe neurons, thus suggesting that the use of antidepressants by pregnant women can induce depression in fetuses due to alterations in their neural development.

OBJETIVO: Avaliar as possíveis alterações ocorridas em nível macroscópico e microscópico de fetos de ratas submetidas ao tratamento com fluoxetina e imipramina durante o período "crítico" da gestação. MÉTODO: Quinze ratas, posteriormente ao acasalamento, foram divididas em três grupos experimentais (n = 5): G1, tratadas com 10mg/kg/dia de fluoxetina; G2, tratadas com 10mg/kg/dia de cloridrato de imipramina, e G3 (controle), tratadas com 10mg/kg/dia de solução fisiológica a 0,9 por cento, no 9º, 10º e 11º dias de prenhez das ratas. Posteriormente à cesária, no 21º dia de prenhez, analisou-se macroscopicamente o peso fetal e placentário. Os fetos foram fixados e houve a remoção do encéfalo para pesagem e preparação das lâminas do tecido neuronal para contagem de neurônios do lobo frontal. RESULTADOS: O G1 e G2 apresentaram maior peso fetal. O G1 apresentou maior peso placentário, diferindo do G2 e G3 (p < 0,01). De forma diferente, o G2 possuiu maior peso encefálico, diferindo do G3 e G1 (p < 0,01). G1 não diferiu estatisticamente do grupo controle (p > 0,01). O G3 exibiu maior número de neurônios, por área, do lobo frontal em relação a G1 e G2 (p < 0,01). CONCLUSÃO: A adoção dos antidepressivos causou, nos fetos, aumento de peso e redução da contagem de neurônios do lobo frontal, sugerindo que a indicação de antidepressivos às gestantes pode induzir a depressão nos fetos por alterações em seu neurodesenvolvimento.

Topiramate induced histopathological changes in placenta of rats.

Effect of topiramate, an antiepileptic drug, on the development of conceptus and its safety during pregnancy has been investigated in experimental rats. Rats were treated with topiramate dissolved in tap water in the doses of 40. 100 and 200 mg/kg body weight from day 9 to 12 of gestation through oral route. Fetuses along with placenta were collected for examination on day 21 of gestation after sacrificing the pregnant rats with deep ether anaesthesia. The placenta showed neither significant reduction in weight as compared to the controls nor any overt anomaly. However. on microscopic examination all treated groups showed similar structural changes which increased in severity with increase in the dose of the drug. The deciduas basalis showed thickening, heamorrhage and increased fibrinoid deposit. Disproportionately increased frequency of vacuolated giant cells was observed in the basal zone whereas frequently broken trichorial membrane. homogenous labyrinthine septa and increased fetal mesenchyme were observed in the placental barrier. The results suggested that topiramate induced dose dependent deleterious changes in the structure of placenta, therefore it should be used with caution during pregnancy.

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.

Morphological changes in human placenta of wet snuff users

Wet snuff is commonly used by both males and females in different parts of Pakistan. Apart from other ingredients, tobacco is the major component of snuff. Adverse effects of smoking on morphology of human placenta have been shown by some previous studies. But snuff is not considered as dangerous as smoking during pregnancy. This study was designed to see the effects of snuff on morphology of human placenta. In present study total 80 human placentae, 40 from normal and 40 from snuff users were used. This study was carried out in the Department of Anatomy Basic Medical Sciences Institution [BSMI] Karachi. Duration of study was six months. Samples were obtained from Gynaecology and Obstetric unit-I JPMC. Placentae washed well with running tap water to remove blood clots. Umbilical cord and other membranes were removed and placenta gently squeezed to expel the foetal blood. Gross features like weight, diameters, central thickness and attachment of umbilical cord were noted in normal and snuff users' placentae. Then placentae were preserved in 10% formalin for at least five days before the sectioning for micromorphology. Placentae divided in two groups-A and B. 4 micro m thick sections of the tissue were taken on rotary microtome and stained with H and E, Mallorys trichrome and methanamine silver for different histological observations. Mircromorpholgical changes have been observed in placentae of snuff users leading to loss of functional components of placentae. This loss of functional component may have deleterious effects on outcome of pregnancy. No significant gross morphological changes were found in snuff user placentae. Wet snuff effect the micro-morphology of placenta leading to loss of functional component and in turn effects the exchange of materials between mother and foetus which may leads to intrauterine growth retardation. Loss of trophoblasts may lead to hormonal imbalance necessary for normal pregnancy and this imbalance can cause premature labour. Nocotine can cross the placental barrier[2], which may produce foetal tachycardia

Effects of Aspartame on Maternal-Fetal and Placental Weights, Length of Umbilical Cord and Fetal Liver: A Kariometric Experimental Study / Efectos del Aspartame sobre el Peso Materno-Fetal y Placentario, Largo del Cordón Umbilical e Hígado Fetal: Un Estudio Cartométrico Experimental

Aspartame is a synthetic sweetener consumed by more than half the adult population in 75 countries. Their metabolites can be toxic, principally to the liver and retina, and there are few studies on the use of aspartame in gestation. Twenty pregnant rats were weighed and allocated randomly (n=5 per group) to receive 14 mg/kg aspartame or water by oral-gastric drip. Treated Tl: aspartame diluted in water at room temperature; Treated T2: aspartame diluted in water heated to 40° C; control Cl: water at room temperature; and control C2: water heated to 40° C. Placentas were weighed, umbilical cords measured and 1000 nuclei of fetal hepatocytes (250 from each group) were analyzed morphometrically utilizing the technique of kariometry, with application of the Mann-Whitney U-Test. There were reductions in mean placental and maternal-fetal weights, in umbilical-cord length, and the majority of kariometric parameters of the hepatocytes in the group treated with aspartame diluted in distilled water at room temperature. Reduction of placental and maternal-fetal weights occurred, shortening of the umbilical cord, and decrease in kariometric parameters in fetal hepatocyte nuclei after administration of aspartame diluted in distilled water at 40°C temperature. The use of aspartame during gestation can be prejudicial to the fetus.

El aspartame es un endulzante sintético consumido por más de la mitad de la población adulta, en 75 países. Sus metabolitos pueden ser tóxicos, principalmente en el hígado y retina y hay algunos estudios sobre el aspartame en el embarazo. Veinte ratas preñadas fueron pesadas y distribuidas aleatoriamente (n=5 por grupo) y recibieron 14 mg/Kg de aspartame o agua por vía oral- gástrica. Tratamiento 1: aspartame diluido en agua a temperatura ambiente; Tratamiento T2: aspartame diluido en agua tibia a 40 °C; control Cl: agua a temperatura ambiente, y control C2: agua tibia a 40° C. Las placentas fueron pesadas, el cordón umbilical medido y 1000 núcleos de hepatocitos fetales (250 de cada grupo) se analizaron morfométricamente utilizando la técnica de canometría con aplicación del Test U de Mann-Whitney U-Test. En el grupo tratado con aspartame diluido en agua a temperatura ambiente, hubo reducción en los pesos promedios de la placenta y materno-fetal, largo del cordón umbilical y en la mayoría de los parámetros cartométricos de los hepatocitos. Lo mismo ocurrió en el grupo tratado con aspartame diluido en agua a 40 °C. El uso del aspartame durante las gestación puede ser perjudicial para el feto.

Morphological, biochemical and ultrastructural changes in the pregnant rat placenta and the liver of their fetuses treated with folic acid and / or gamma radiation

The efficacy of antioxidant supplementation and oxidative stress of gamma irradiation for and during pregnancy is poorly established. The present study aimed to detect the toxic effects of high dose of folic acid and / or gamma radiation on the placenta of pregnant rat and the liver of their fetuses. Pregnant albino rats were divided into four groups. The first group served as a control, the second group received oral intake of folic acid [5 mg/kg] from the 5th to 20th day of gestation, the third group was irradiated with gamma radiation [3Gy, as fractionated doses [1Gy/ 3 times] on each 5th, 10th and 15th days of gestation, the fourth group was imanaged with combined treatment. The pregnant rats were sacrified after 20 days of pregnancy and samples were taken from the blood, placenta and the fetal liver for the morphological, biochemical and electron microscopic studies. The present results showed a significant elevation in serum gamma glutamyltransferase [gammaGT], lactate dehydrogenase [LDH] in placental tissue of pregnant rats associated with an increase of phosphorus content in liver of fetuses. Fetal malformations including: protrusion, anotia, short neck dactylomegaly, subcutaneous haemorrhage, paralysis in the fore limbs and congested blood vessels. The ultrastructural changes revealed sever damage in the placenta following folic acid administration and / or exposure to whole body gamma radiation. Also the fetal liver showed an appearent signs of damage under the combined treatment. The obtained changes were represented by: dilatation of the blood sinsoids, swollen mitochondria, fragmented rough endoplasmic reticulum and necrosis. It could be concluded that administration of folic acid and/or exposure to gamma radiation during pregnancy induced morphological, biochemical and ultrastructural changes in both placenta of the pregnant rats and liver of their fetuses

Comparison of oxytocin administration before and after placental delivery in the prevention of postpartum hemorrhage

Post partum hemorrhage as a consequence of uterine atony represents a leading of maternal morbidity and mortality. Prophylactic oxytocin, commonly administered after fetal or placental delivery, reduces the incidence of post partum hemorrhage by up to 40%. Evidence from studies suggests that giving oxytocin before rather than after placental expulsion, minimizes third - stage duration and blood loss. The general obiective was to compare oxytocin administration before and after placental delivery in the prevention of post partum hemorrhage. This research was a prospective randomized clinical trial study, parturients who presented for vaginal delivery were randomized to receive oxytocin, 20 units in a 500 ml serum Ringer, beginning upon delivery of either the fetal anterior shoulder or placenta. For all patients, the third stage of labor was similar. Patients were excluded if they had a pervious ceasarean section, multiple gestation, an tepartum hemorrhage, or bleeding disorder. A total 70 patients were enrolled: 35 in the before placenta group and 35 in the after placenta group. The groups were similar with respect to gestational age, maternal age, fetal weight, Labor duration, parity and pervious postpartum hemorrhage. The incidence of post partum hemorrhage were significantly between the two groups [91 +/- 22 ml VS 127 +/- 50 ml]. There were significant differences between two groups in third stage duration [4 +/- 2 min VS 7 +/- 1 min], but there were no significant differences between the two groups with no incidence of retained placenta. The administration of prophylactic oxytocin before placental delivery significantly reduces the incidence of postpartum hemorrhage or third stage duration when compared with oxytocin after placental delivery

[Toxicity effects on aluminium chloride on uterus and placenta of pregnant mice]

Aluminium has been known to cause toxic effects on organ systems. Although the knowledge on aluminium [AL] toxicity has markedly improved in recent years, information concerning the reproductive toxicity of this element is still very limited. The purpose of this study was to assess the effect of graded dose of aluminium chloride administered to pregnant mice on their placenta and uterine in a short time. This study was performed on plug-positive female NMRI [National Medical Research Institute] mice that were randomly divided into six groups [12 mice in each group]. Three groups of plug- positive female NMRI mice were given IP injections of ALCL[3] at 150 mg/kg on days 10, 11 and 12 of gestation, respectively. Three other groups were given normal saline on the same days as control groups. Mice were killed on day 15 of gestation, the weight and diameter of placenta were recorded. Both placenta and uterus were examined with stereomicroscope and also uterus fixed and stained for microscopic examination. In all experimental groups, in 14.3%, 13.8% and 13.3% of fetuses, placenta showed abnormal appearance and some degrees of atrophy on days 10, 11, 12 of gestation, respectively that in comparison to control group it was significantly higher [p<0.05]. Also, the diameter of placenta in experimental groups [7.2, 7.2 and 7.3mm respectively] was significantly smaller than control groups [7.6mm] [p<0.05]. The uterine of All treated groups showed hemorrhagic area in external examination and infiltration reaction and dispersed nectrotic foci in myometer in microscopic examination. According to the results, AlCl [3] showed toxic effect on placenta and uterus of pregnant mice. It could explain at least part of teratogenic effects of AlCl [3]

Estudo do efeito teratogênico da ciclofosfamida em ratos: morfologia, morfometria e esterologia do palato fetal / Cyclophosphamide teratogenic effect in rats: morfology, morfometry and stereology of the fetal palate

O objetivo do presente trabalho foi estudar a ação da ciclofosfamida no feto, na placenta, no comprimento do cordão umbilical e no palato de filhotes de ratas tratadas com a droga durante a gestação, foram utilizados 14 ratas albinas rattus norvegicus, variedade wistar, sendo 7 para o grupo controle e 7 para o grupo tratado com a ciclofosfamida, nossos resultados sugerem que a ciclofosfamida é teratogênica para os fetos, compromete o peso fetal, da placenta, o comprimento do cordão umbilical e a histologia do palato duro e mole dos fetos tratados

Ação crônica do napsilato de propoxifeno na prenhez da rata / Chronic effects of propoxyphene napsylate on pregnant rats

O objetivo deste trabalho é avaliar os efeitos do napsilato de propoxifeno sobre a prenhez da rata albina. Para tanto utilizamos 50 ratas prenhes divididas ao acaso em cinco grupos iguais. Todas receberam diariamente, por gavagem, o volume de 1 ml, desde os dias 0 (zero) até o 20 de prenhez, com as seguintes características: grupo I - somente água destilada (controle): grupo II - soluçao aquosa de acácia 2 por cento (veículo); grupos III, IV e V - respectivamente, 5, 15 e 45 mg/kg de peso de napsilato de propoxifeno dissolvido em soluçao de acácia a 2 por cento. Os pesos maternos foram anotados nos dias 0 (zero), 7, 14 e 20 de prenhez; no 20 dia as matrizes foram sacrificadas. Nossos resultados mostraram que os animais tratados com 45 mg/kg do fármaco apresentaram reduçao dos pesos individuais dos fetos como também dos pesos das ninhadas e das placentas. Quanto às outras variáveis apreciadas: número de reabsorçoes, de implantaçoes e de placentas nao houve diferença significante entre os grupos tratados em relaçao ao grupo controle.

Insulinoterapia na prenhez de rats diabéticas: repercussöes fetais e placentárias / Effect of insulin therapy in on pregnancy of diabetic rats: fetal and placental repercussions

O objetivo deste trabalho foi estudar as repercussoes feto-placentárias da insulinoterapia na prenhez de ratas diabéticas. A droga diabetogênica foi aloxana na dose de 42 mg/kg de peso por via intravenosa. Formaram-se cinco grupos experimentais: controle (G1, n=12); diabete moderado nao-tratado (G2, n=10; diabete moderado tratado com insulina (G3, n=11); diabete grave nao-tratado (G4, n=12) e diabete grave tratado com insulina (G5, n=10). Foram obtidos 634 recém-nascidos e respectivas placentas. O resultado perinatal do tratamento com insulina teve relaçao direta com a qualidade do controle glicêmico. O tratamento inadequado do diabete moderado determinou níveis de hiperglicemia moderada nos recém-nascidos, nao interferiu com o peso corporal dos filhotes e diminuiu a proporçao de recém-nascidos grandes para a idade da prenhez (GIP). O controle adequado do diabete grave normalizou a glicemia dos recém-nascidos, aumentou o peso dos filhotes e diminuiu a proporçao de recém-nascidos pequenos para a idade da prenhez (PIP). A administraçao de doses adequadas de insulina no grupo de ratas diabéticas grave diminuiu o peso das placentas mas sem modificar o índice placentário.