No description available.

We used light microscopy to study placental structure of the lizard Sceloporus mucronatus throughout 6 months of embryonic development. Three stages of placental development could be assigned to embryos based on the arrangement of the extraembryonic membranes. A highly vascular choriovitelline placenta was present in the embryonic hemisphere and a nonvascular bilaminar omphalopleure covered most of the abembryonic hemisphere of the egg during embryonic Stages 10-28. A chorioallantoic placenta replaced the choriovitelline placenta by embryonic Stage 29 and an omphaloplacenta covered the abembryonic hemisphere at this stage. The combination of these two placental types occurred in Stage 29-36 embryos. The final stage of placentation, embryonic Stages 37-40, was characterized by an omphalallantoic placenta in the abembryonic hemisphere and a chorioallantoic placenta in the embryonic hemisphere of the egg. The choriovitelline and chorioallantoic placentae are well vascularized, with closely apposed maternal and embryonic blood vessels. These structures are the most likely sites of respiratory exchange. In contrast, the omphaloplacenta and omphalallantoic placentae contain cuboidal or columnar epithelia and these structures may function in histotrophic exchange. Placentation of S. mucronatus is similar to that of predominantly lecithotrophic species in other squamate lineages suggesting that the evolution of this placental morphology is a response to similar factors and is independent of phylogeny.

The interaction between the embryo and fetus with the maternal environment can have both short- and long-term consequences on health and development after birth. In some cases, these changes may be detrimental to the individual, but in other cases these developmental changes may be beneficial and manipulated to produce desired effects. Our interest is to use this concept of fetal programming to improve skeletal muscle development and meat production in ruminants. To achieve this, we targeted the period of gestation when fetal muscle fiber formation occurs. Primary muscle fibers form during embryonic development, and it is this small number of primary muscle fibers that will serve as templates for secondary fiber formation that occurs in the fetus during mid-gestation. Supplementing amino acids that influence blood flow within the reproductive tract is one potential way to provide fetuses with added nutrients during gestation, and this supplementation strategy may be especially useful when the maternal diet is compromised. L-citrulline was chosen for this work because of its long half-life in maternal circulation. This work utilized twin-bearing ewes with a moderate dietary energy restriction to assess the effects of mid-gestational L-citrulline supplementation on umbilical blood flow, placental function, neonatal lamb size, and lamb performance. We hypothesize that i.v. administration of L-citrulline will increase uterine and placental blood flow in gestating ewes and this will improve fetal growth, development, and overall postnatal performance. Blood flow parameters were not influenced by treatment (P>0.05). Circulating levels of progesterone and pregnancy-specific protein B (PSPB) were used as indicators of placental function and were unaffected by treatment administration (P>0.05). A treatment by time interaction was detected in both analyses, but no differences between treatments were detected within any time points. There was no effect of treatment on lamb weights or survival to weaning (P>0.05). Lamb sex effects are absent with the exception that body weights were greater in ewe lambs (P>0.05). There was no effect of treatment on any carcass traits or visceral organ weights assessed, though there was an effect of sex on dressing percentage and pancreas weight with wethers having a greater dressing percentage and heavier pancreases per kg body weight than that of ewes (P<0.05). In summary, contrary to our hypothesis L-citrulline supplementation to pregnant ewes under a minor to moderate metabolic challenge had no impact on blood flow and provided no programming benefit to the lambs. / Master of Science / The global population continues to grow, along with the consumption of animal protein. This can be met with increasing the numbers of animals within our food production systems, however, there is also increasing pressure for livestock production systems to produce more while utilizing less space and resources. And simultaneously, we face growing concerns about climate change, its impacts on agriculture, and the role of agriculture in both the cause and any future solution. To combat both these issues, the efficiency of our livestock systems needs to improve with each individual animal becoming much more efficient. This increase in efficiency can occur in many ways including reproductive efficiency, feed efficiency, and in overall producing more meat per individual. The improvement in efficiency of an animal can begin in the womb. Livestock in meat production spend 35-40% of their life within the uterus being nourished by their mother. The interactions the embryo and fetus have with the maternal environment during this time can have both short- and long-term impacts on health and development after birth. In some cases, these changes may be detrimental to the individual, but in other cases these developmental changes may be beneficial and manipulated to produce the desired effects. Thus, it is important to understand the impact of these fetal-maternal interactions as it directly affects both fetal growth and growth and development after birth. This concept is known as fetal programming. Our interest is to use this concept to improve skeletal muscle development and meat production in cattle and sheep. To achieve this, we targeted the period of pregnancy when fetal muscle formation occurs. Primary muscle fibers form early in pregnancy, and it is this small number of primary muscle fibers that will serve as templates for secondary fiber formation that occurs in the fetus during mid-pregnancy. Supplementing amino acids that influence blood flow within the reproductive tract is one potential way to provide fetuses with added nutrients during pregnancy, and this supplementation strategy may be especially useful when the maternal diet is compromised. L-citrulline was chosen for this work because of its long half-life in maternal circulation. This work utilized twin-bearing ewes with a moderate dietary energy restriction to assess the effects of L-citrulline supplementation on blood flow, placental function, newborn lamb size, and lamb performance. We hypothesize that intravenous administration of L-citrulline will increase uterine and placental blood flow in pregnant ewes and this will improve fetal growth, development, and overall postnatal performance. There was no beneficial effect on blood flow to the fetus and on placental function. Additionally, there were very minimal effects on carcass traits or internal organ weights assessed. In summary, contrary to our hypothesis L-citrulline supplementation to pregnant ewes under a moderate metabolic challenge had no impact on blood flow and provided no programming benefit to the lambs. We can conclude that the potential benefit of amino acid supplementation was not realized in our sheep model.

Submitted by (lucia.rodrigues@ufrpe.br) on 2016-06-10T13:14:18Z No. of bitstreams: 1 Welma Emidio da Silva.pdf: 1500896 bytes, checksum: 7ff17715c3c5e19b309e27006eee6e14 (MD5) / Made available in DSpace on 2016-06-10T13:14:18Z (GMT). No. of bitstreams: 1 Welma Emidio da Silva.pdf: 1500896 bytes, checksum: 7ff17715c3c5e19b309e27006eee6e14 (MD5) Previous issue date: 2012-02-16 / Several authors have reported that metronidazole crosses the placental barrier and enters the fetal circulation and is still excreted in breast milk. Thus, not recommend the use of this drug in pregnant women and also the breastfeeding suspension for 12-24 hours after administration. However, some investigators report lack of evidence that the use of metronidazole is associated with increased risk teratogenic when administered during pregnancy is therefore unnecessary waiting for the termination of pregnancy for treatment with this drug. Thus, this study aimed to analyze the effect of administration of metronidazole during pregnancy on placental and fetal development of albino rats. 30 albino rats were used, which were divided into two groups. GROUP I - pregnant rats treated with placebo and GRUPOII - pregnant rats treated with metronidazole. The metronidazole was administered daily by gavage at a dose of 130 mg / kg for 7, 14 and 21 days of gestation. The results showed that the treated group a significant reduction in the number of deployment sites, the total area of the placental disc and the constituents of the layers of the labyrinth and trofospôngio. The histochemical analysis revealed no significant changes in the content of collagen and elastic fibers and reticular. The test showed TUNEL apoptotic activity at the site of implantation and placental development 14 days regardless of treatment. We did not observe any evidence of malformation in the head, trunk and limbs of neonates. However, a significant reduction in weight and number of neonates in the group treated with metronidazole compared to control. Thus, we conclude that metronidazole in pregnant rats administered orally at a dosage of 130 mg / kg, in two thirds of early pregnancy interferes with the interaction blastocyst endometrium, in placental and fetal development, suggesting that this drug should be avoided in the early stages of pregnancy. / Vários autores relatam que o metronidazol atravessa a barreira placentária e penetra na circulação fetal, sendo ainda excretado no leite materno. Desta forma, não recomendam o uso dessa droga em mulheres gestantes e também a suspensão do aleitamento materno por 12 a 24 horas após a administração do mesmo. Entretanto alguns pesquisadores relatam faltar evidências de que o uso do metronidazol está associado com o aumento de riscos teratogênicos quando administrado durante a gestação sendo, portanto, desnecessário a espera do termino da gestação para o tratamento com essa droga. Assim, a presente pesquisa teve como objetivos analisar o efeito da administração do metronidazol durante a prenhez, sobre o desenvolvimento placentário e fetal de ratas albinas. Foram utilizadas 30 ratas albinas, que foram divididas em dois grupos. GRUPO I – ratas prenhas tratadas com placebo e GRUPOII – ratas prenhas tratadas com metronidazol. O metronidazol foi administrado por gavagem na dosagem diária de 130 mg/kg durante 7, 14 e 21 dias de gestação. Os resultados mostraram que no grupo tratado houve redução significativa do número de sítios de implantação, da área total do disco placentário e nos elementos constituintes das camadas do labirinto e trofospôngio. A análise histoquímica não revelou alterações significativas no teor de fibras colágenas, elásticas e reticulares. O teste de TUNEL mostrou atividade apoptótica nos sítios de implantação e placentas com 14 dias de desenvolvimento independente do tratamento. Não foram observados nenhum indício de malformação na cabeça, tronco e membros dos neonatos. No entanto, houve uma redução significativa no número e peso dos neonatos no grupo tratado com o metronidazol em relação ao controle. Assim, concluímos que o metronidazol administrado em ratas prenhes, por via oral, na dosagem de 130 mg/Kg, nos dois terços iniciais da gestação interfere na interação blastocisto endométrio, no desenvolvimento placentário e fetal, sugerindo que o uso desse medicamento deve ser evitado nas fases iniciais da gestação.

CD146 est une glycoprotéine appartenant à la superfamille des immunoglobulines, exprimée de manière ubiquitaire sur l'endothélium, principalement au niveau des jonctions. Une forme soluble de CD146 (CD146s) est générée par clivage de la forme membranaire par un mécanisme dépendant des métalloprotéases. CD146 et CD146s interviennent dans le maintien de l'intégrité de l'endothélium, la transmigration endothéliale des monocytes et possèdent des propriétés angiogéniques. Les concentrations sériques de CD146s varient au cours de pathologies liées à une atteinte vasculaire. Notre travail a pour but d'étudier l'implication de CD146s dans deux contextes indépendants: la physiopathologie obstétricale et la sclérodermie systémique. La première partie de notre travail a consisté à analyser le rôle de la molécule au cours de la grossesse. Dans le placenta normal, l'expression de CD146 est restreinte aux trophoblastes possédant des capacités de migration et d'invasion, les trophoblastes extra-villeux (EVT). Ces EVT remodèlent les artères utérines spiralées afin d'établir une circulation foeto-maternelle. Au cours de ce processus, appelé pseudo-vasculogenèse, les EVT acquièrent un phénotype endothélial. De plus, l'expression placentaire de CD146 et les concentrations de CD146s varient au cours de grossesses pathologiques. L'hypothèse de notre travail est que CD146s régulerait les capacités invasives des EVT et interviendrait dans le développement placentaire. / CD146 is a member of the immunoglobulin superfamily. This is a membrane glycoprotein localized at the endothelial junction. CD146 also exists as a soluble form in the plasma (sCD146), generated by proteolysis of membrane CD146 through a mechanism involving metalloproteinases. CD146 and sCD146 are involved in endothelium integrity, monocyte transmigration and display angiogenic properties. CD146s level variations are observed in vascular pathologies. The aim of our work was to investigate the role of sCD146 in obstetrical physiopathology and in systemic sclerosis. In a first part, the involvement of our molecule was analyzed during pregnancy. In normal placenta, CD146 is expressed in intermediate and extra-villous trophoblasts (EVT), presenting migratory and invasive properties. EVT invade the spiral arteries and convert from an epithelial to an endothelial phenotype during the pseudo-vasculogenesis process. Moreover, CD146 placental expression and sCD146 levels are modified during pathologic pregnancies. We hypothesized that sCD146 could regulate EVT invasiveness and placental development. Using placental villous explants, we demonstrated that sCD146 inhibits EVT outgrowth. Consistently, we showed that sCD146 inhibits the ability of EVT cells (HTR8/SVneo) to migrate, invade and form tubes in Matrigel®. The involvement of sCD146 in human pregnancy was investigated by evaluation of sCD146 levels in 50 pregnant women. We observed physiological down-regulation of sCD146 throughout pregnancy. These results prompted us to investigate the effect of prolonged sCD146 administration in a rat model of pregnancy.

Submitted by (lucia.rodrigues@ufrpe.br) on 2016-06-07T12:41:36Z No. of bitstreams: 1 Ismaela Maria Ferreira de Melo.pdf: 1484897 bytes, checksum: 412f7fc7d3537d1d040e74378ac1ef3c (MD5) / Made available in DSpace on 2016-06-07T12:41:36Z (GMT). No. of bitstreams: 1 Ismaela Maria Ferreira de Melo.pdf: 1484897 bytes, checksum: 412f7fc7d3537d1d040e74378ac1ef3c (MD5) Previous issue date: 2012-02-07 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Fluoroquinolones are frequently used in human and veterinary medicine for treatment and prevention of disease respiratory tract, digestive and urinary. Within this group we can highlight the enrofloxacin, a drug that presents a wide spectrum of activity against Gram positive and Gram negative. It is known that fluoroquinolones are the property of crossing the placenta and may have adverse effects on the developing fetus, especially when you consider that more than half of pregnancies are unplanned, and thus a large number of women may be exposed to potentially these drugs during the first trimester of pregnancy. However, the mechanisms of these adverse effects are still unknown. Thus, the present study was to evaluate the effect of enrofloxacin in pregnant rats on placental development and offspring. Enrofloxacin (Baytril ®) was administered at a dose of 5 mg / kg daily intramuscular throughout pregnancy. The placentas were analyzed morphologically, morphometrically and immunohistochemical tests for seven, fourteen and twenty days of pregnancy. The results showed that the treated group there was significant reduction in the number of implantation sites, weight and placental total area of the disk at fourteen and twenty days of development, and quantitative changes in the constituents of the layers of the labyrinth, trophoblastic giant cells and trofospongio of the placenta. There were observed no evidence of malformation in the head, trunk and limbs of neonates. However, there was a significant reduction in the number and weight of neonates in enrofloxacin-treated group compared to control, but without affecting its length. There was no change in the histochemical analysis, however, the TUNEL test showed stronger apoptotic activity in the placentas with only 14 days of development in the treated group compared to control. With this we conclude that enrofloxacin when administered at a dose of 5 mg/kg in rats during pregnancy interferes with placental development by altering the constituents of the placenta and increase apoptosis in the middle third of pregnancy, and reflecting the reduction in the number and weight of neonates. / As fluoroquinolonas são freqüentemente usadas na medicina humana e veterinária para tratamento e prevenção de doenças do trato respiratório, digestivo e urinário. Dentro deste grupo podemos destacar a enrofloxacina, um fármaco que apresenta um elevado espectro de atividade frente bactérias Gram positivo e Gram negativo. Sabe-se que as fluoroquinolonas têm a propriedade de atravessar a placenta podendo ter efeitos adversos no feto em desenvolvimento, principalmente se levarmos em consideração que mais da metade das gestações não são planejadas, e assim, um grande número de mulheres pode ser potencialmente expostas a estes fármacos durante o primeiro trimestre de gravidez. No entanto, os mecanismos desses efeitos adversos ainda são desconhecidos. Assim, a presente pesquisa teve como objetivo avaliar o efeito da enrofloxacina em ratas prenhas no desenvolvimento da placenta e da prole. A enrofloxacina (Baytril®) foi administrada na dose de 5 mg/kg, diariamente, via intramuscular, durante toda a gestação. As placentas foram analisadas morfologicamente, morfometricamente e imunohistoquimicamente aos sete, quatorze e vinte dias de prenhez. Os resultados mostraram que no grupo tratado houve redução significativa do número de sítios de implantação, do peso e área total do disco placentário aos quatorze e vinte dias de desenvolvimento, e alterações quantitativas nos elementos constituintes das camadas do labirinto, trofospongio e células trofoblasticas gigantes da placenta. Não foram observados nenhum indício de malformação na cabeça, tronco e membros dos neonatos. No entanto, houve uma redução significativa no número e peso dos neonatos no grupo tratado com a enrofloxacina em relação ao controle, porém sem afetar o seu comprimento. Não houve alteração na análise histoquímica, porém, o teste de TUNEL mostrou atividade apoptótica mais intensa apenas nas placentas com 14 dias de desenvolvimento do grupo tratado em relação ao controle. Com isso concluímos que a enrofloxacina quando administrada na dosagem de 5 mg/kg durante prenhez em ratas interfere no desenvolvimento placentário, por alterar os elementos constituintes da placenta e aumentar a apoptose no terço médio da gestação, tendo como reflexo a redução no número e peso dos neonatos.

No description available.

L'obésité maternelle peut prédisposer aux pathologies métaboliques à l'âge adulte. Une perte de poids préconceptionnelle est recommandée aux femmes obèses, mais ses effets sur la croissance fœto-placentaire et la santé de la descendance adulte sont encore peu connus. Les objectifs de cette thèse étaient d’étudier les effets des trajectoires pondérales maternelles sur le phénotype de la descendance à terme et à l’âge adulte, ainsi que sur l’expression génique. Les descendants de mères obèses présentent une restriction de croissance fœtale, associée à des altérations d’expression des gènes de la machinerie épigénétique dans le foie fœtal et le labyrinthe placentaire. Notre étude souligne la sensibilité particulière de la machinerie d’acétylation des histones au métabolisme maternel. À l'âge adulte, les mâles nés des mères obèses développent une obésité aggravée lorsqu'ils sont exposés à un environnement obésogène. La perte de poids maternelle préconceptionnelle améliore la croissance fœtale et normalise le poids à l’âge adulte. Elle est donc bénéfique pour la descendance. Cependant, certains effets de l’obésité, corrigée par l’intervention nutritionnelle, sont conservés car le poids fœtal et l’expression d’une partie de gènes restent altérés. Ce travail apporte des premiers éléments sur les mécanismes du conditionnement développemental par les trajectoires pondérales maternelles. / Maternal obesity (OB) impacts fetal growth and adult offspring phenotype. It is still unknown whether the currently recommended preconceptional weight loss (WL) for obese women is beneficial for feto-placental growth and adult offspring health. The objectives of this thesis were to assess the effects of maternal weight trajectories on offspring phenotype at term and in adulthood, as well as gene expression in placenta and fetal liver. At E18.5, fetuses from obese females presented a fetal growth restriction (FGR); this FGR was almost completely abolished by maternal WL. Placental and hepatic expression of epigenetic machinery genes was affected by maternal OB, especially the histone acetylation pathway. Maternal WL normalized the expression of only a subset of these genes. Males born to OB mothers gained weight faster under high-fat diet than males born to control mothers; maternal WL rescued this phenotype. These results show that expression of epigenetic machinery genes and in particular histone acetylation regulators, is highly sensitive to maternal obesity. Preconceptional WL alleviates the effects of OB on fetal and adult weight but some effects of obesity cured by nutritional intervention were retained in offspring phenotype at term. This study is an important step toward understanding the mechanisms linking maternal nutrition to fetal growth and adult health.