RESUMO
Increased O-Linked ß-N-acetylglucosamine (O-GlcNAc) is observed in several pathologies, and unbalanced O-GlcNAcylation levels favor endothelial dysfunction. Whether augmented O-GlcNAc impacts the uterine artery (UA) function and how it affects the UA during pregnancy remains to be elucidated. We hypothesized that glucosamine treatment increases O-GlcNAc, leading to uterine artery dysfunction and this effect is prevented by pregnancy. Pregnant (P) and non-pregnant (NP) Wistar rats were treated with glucosamine (300 mg/kg; i.p.) for 21 days. Concentration response-curves (CRC) to acetylcholine (in the presence or absence of L-NAME) and sodium nitroprusside were performed in UAs. In NP rats, glucosamine treatment increased O-GlcNAc expression in UAs accompanied by decreased endothelium-dependent relaxation, which was abolished by L-NAME. Endothelial nitric oxide synthase (eNOS) activity and total Akt expression were decreased by glucosamine-treatment in NP rats. Further, NP rats treated with glucosamine displayed increased glycogen synthase kinase 3 beta (GSK3ß) activation and O-GlcNAc-transferase (OGT) expression in the UA. P rats treated with glucosamine displayed decreased O-GlcNAc in UAs and it was accompanied by improved relaxation to acetylcholine, whereas eNOS and GSK3ß activity and total Akt and OGT expression were unchanged. Sodium nitroprusside-induced relaxation was not changed in all groups, indicating that glucosamine treatment led to endothelial dysfunction in NP rats. The underlying mechanism is, at least in part, dependent on Akt/GSK3ß/OGT modulation. We speculate that during pregnancy, hormonal alterations play a protective role in preventing O-GlcNAcylation-induced endothelial dysfunction in the UAs.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Glucosamina/farmacologia , Glicogênio Sintase Quinase 3 beta/fisiologia , Artéria Uterina/efeitos dos fármacos , Animais , Endotélio Vascular/fisiologia , Feminino , N-Acetilglucosaminiltransferases/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Artéria Uterina/fisiologia , Vasodilatação/efeitos dos fármacosRESUMO
Preeclampsia currently remains one of the leading causes of death and severe maternal morbidity. Although its prevalence is still underestimated in some places due to underreporting, preeclampsia is a disease that health professionals need to know how to deal with and take action. For this reason, the studies about the theme remain along with the advances in their understanding that often implies improvement and change of concepts and conducts. The complexity of its etiology is a challenge and requires further studies for its full understanding. Apparently, poor adaptation of the maternal organism to the conceptus, marked by the nonoccurrence of changes in the uterine spiral arteries, determines a series of systemic repercussions that compound the various forms of preeclampsia presentation. In recent years, the use of acetylsalicylic acid to prevent cases of early onset of the disease has been consolidated and, alongside, studies have advanced the development of accessible and effective methods of identifying women at risk of preeclampsia. The aim of this review is to discuss updates on the occurrence, concept, pathophysiology, repercussion, prevention, and prediction of preeclampsia.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Aspirina/uso terapêutico , Placenta/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Artéria Uterina/fisiopatologia , Proteína ADAM12/genética , Proteína ADAM12/metabolismo , Adulto , Biomarcadores/metabolismo , Feminino , Galectinas/genética , Galectinas/metabolismo , Humanos , Fluxometria por Laser-Doppler , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Placenta/irrigação sanguínea , Placenta/diagnóstico por imagem , Placenta/efeitos dos fármacos , Pré-Eclâmpsia/diagnóstico por imagem , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/prevenção & controle , Gravidez , Proteínas da Gravidez/genética , Proteínas da Gravidez/metabolismo , Proteína Plasmática A Associada à Gravidez/genética , Proteína Plasmática A Associada à Gravidez/metabolismo , Prognóstico , Fatores de Risco , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/efeitos dos fármacos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE:: To evaluate the effects of enoxaparin and unfractionated heparin (UFH) administered in prophylactic and therapeutic doses on fetal vessels in healthy pregnant Wistar rats, according to Doppler velocimetry measurements. METHODS:: Fifty animals were assigned to one of five groups: controls (saline), prophylactic and therapeutic enoxaparin (1 and 2 mg/kg/day, respectively), and prophylactic and therapeutic UFH (72 and 400 UI/kg/day, respectively). Uterine horns were examined by ultrasound for identification of live fetuses. A sample of these fetuses underwent Doppler velocimetry. Spectral curves, peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the middle cerebral artery, ductus venosus, and umbilical artery were investigated. Differences were considered statistically significant when p<0.05. RESULTS:: No significant differences in PSV, PI, or RI values were observed among the groups. CONCLUSION:: Doppler velocimetry measurements revealed no significant effects of enoxaparin or unfractionated heparin on fetal vessels in pregnant Wistar rats.
Assuntos
Anticoagulantes/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Enoxaparina/farmacologia , Feto/irrigação sanguínea , Heparina/farmacologia , Artéria Cerebral Média/efeitos dos fármacos , Artérias Umbilicais/efeitos dos fármacos , Artéria Uterina/efeitos dos fármacos , Animais , Ecocardiografia Doppler de Pulso/métodos , Feminino , Artéria Cerebral Média/fisiopatologia , Modelos Animais , Gravidez , Ratos Wistar , Ultrassonografia Pré-Natal/métodos , Artérias Umbilicais/fisiopatologia , Artéria Uterina/fisiopatologia , Aumento de Peso/efeitos dos fármacosRESUMO
Lysophosphatidic acid (LPA) affects several female reproductive functions through G-protein-coupled receptors. LPA contributes to embryo implantation via the lysophospholipid LPA3 receptor. In the present study we investigated the participation of endogenous LPA signalling through the LPA3 receptor in vascularisation and decidualisation, two crucial events at the maternal-fetal interface. Pregnant rats were treated with diacylglycerol pyrophosphate (DGPP), a highly selective antagonist of LPA3 receptors, on Day 5 of gestation. Pregnant rats received intrauterine (i.u.) injections of single doses of DGPP (0.1mgkg-1) in a total volume of 2µL in the left horn (treated horn) in the morning of GD5. DGPP treatment produced aberrant embryo spacing and increased embryo resorption. The LPA3 receptor antagonist decreased the cross-sectional length of the uterine and arcuate arteries and induced histological anomalies in the decidua and placentas. Marked haemorrhagic processes, infiltration of immune cells and tissue disorganisation were observed in decidual and placental tissues from sites of resorption. The mRNA expression of three vascularisation markers, namely interleukin 10 (Il10), vascular endothelial growth factor (Vegfa) and vascular endothelial growth factor receptor 1 (Vegfr1), was reduced at sites of resorption from Day 8. The results show that the disruption of endogenous LPA signalling by blocking the LPA3 receptor modified the development of uterine vessels with consequences in the formation of the decidua and placenta and in the growth of embryos.
Assuntos
Decídua/metabolismo , Lisofosfolipídeos/metabolismo , Neovascularização Fisiológica/fisiologia , Placenta/metabolismo , Receptores de Ácidos Lisofosfatídicos/metabolismo , Transdução de Sinais/fisiologia , Animais , Decídua/efeitos dos fármacos , Difosfatos/farmacologia , Implantação do Embrião/fisiologia , Feminino , Glicerol/análogos & derivados , Glicerol/farmacologia , Interleucina-10/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Placenta/irrigação sanguínea , Placenta/efeitos dos fármacos , Gravidez , Ratos , Receptores de Ácidos Lisofosfatídicos/agonistas , Transdução de Sinais/efeitos dos fármacos , Artéria Uterina/efeitos dos fármacos , Artéria Uterina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVES: This study investigated the influence of vaginal progesterone on uterine circulation in asymptomatic twin gestations. STUDY DESIGN: This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. We included all trial participants who had undergone uterine artery pulsatility index evaluation at the time of randomization. During each ultrasound examination, the uterine artery pulsatility index was evaluated transabdominally. The mean uterine artery pulsatility index between the progesterone and placebo groups were compared for each gestational age, starting between 18 to 34 weeks and 6days and were analyzed at three (Time 1), six (Time 2) and nine (Time 3) weeks after randomization. RESULTS: The final analysis included 128 women in the progesterone group and 122 women in the placebo group. The baseline characteristics were similar in both groups. No difference in the mean uterine artery pulsatility index was observed between the progesterone and placebo groups at each week of gestation or throughout gestation. CONCLUSIONS: In twin pregnancies, the use of vaginal progesterone in the second half of pregnancy does not influence uterine circulation.
Assuntos
Progesterona/administração & dosagem , Ultrassonografia Doppler , Artéria Uterina/efeitos dos fármacos , Administração Intravaginal , Adulto , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Gravidez , Resultado da Gravidez , Gravidez de Gêmeos , Ultrassonografia Pré-Natal , Artéria Uterina/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVES: To evaluate the effects of transdermal nitroglycerin (GTN) and sildenafil citrate on Doppler velocity waveforms of the uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) arteries in pregnancies with intrauterine growth restriction (IUGR). METHODS: This was a prospective study of 35 singleton pregnancies (gestational age, 24-31 weeks) with IUGR and abnormal UtA and UA Doppler waveforms. We compared maternal arterial blood pressure and Z-scores of the pulsatility index (PI) of UtA, UA and fetal MCA before and after application of a transdermal GTN patch (average dose, 0.4 mg/h), oral sildenafil citrate (50 mg) or placebo. Statistical analysis was performed by ANOVA for paired samples. RESULTS: There was a significant decrease in UtA-PI after application of GTN (21.0%) and sildenafil citrate (20.4%). A significant reduction in UA-PI was also observed for both GTN (19.1%) and sildenafil citrate (18.2%). There was no difference in UtA- and UA-PI when the GTN and sildenafil groups were compared. No changes in Doppler velocimetry were observed in the placebo group and no significant change in MCA-PI was observed in any group. Maternal arterial blood pressure decreased with administration of both GTN and sildenafil citrate in those with pre-eclampsia. CONCLUSION: The use of transdermal GTN or sildenafil citrate in pregnancies with IUGR is associated with a significant reduction in both UtA and UA Doppler PI, as well as maternal arterial blood pressure. Neither drug affected the MCA-PI. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Assuntos
Nitroglicerina/farmacologia , Insuficiência Placentária/tratamento farmacológico , Citrato de Sildenafila/farmacologia , Vasodilatadores/farmacologia , Administração Cutânea , Adulto , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Método Duplo-Cego , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/tratamento farmacológico , Retardo do Crescimento Fetal/fisiopatologia , Humanos , Artéria Cerebral Média/efeitos dos fármacos , Artéria Cerebral Média/embriologia , Artéria Cerebral Média/fisiologia , Nitroglicerina/administração & dosagem , Insuficiência Placentária/diagnóstico por imagem , Insuficiência Placentária/fisiopatologia , Gravidez , Estudos Prospectivos , Fluxo Pulsátil/efeitos dos fármacos , Citrato de Sildenafila/administração & dosagem , Resultado do Tratamento , Ultrassonografia Pré-Natal , Artérias Umbilicais/efeitos dos fármacos , Artérias Umbilicais/fisiologia , Artéria Uterina/efeitos dos fármacos , Artéria Uterina/fisiologia , Vasodilatadores/administração & dosagem , Adulto JovemRESUMO
The uterus plays an essential role in mammalian reproduction and is a target of several hormonal protocols used to improve fertility in cattle. Many studies highlighted the importance of eCG treatment following fixed-time artificial insemination in improving follicular growth, ovulation and pregnancy rates in cattle. Moreover, eCG has been implicated in angiogenesis, leading to important changes in uterine blood flow and vascularisation. However, there is still a lack of information regarding the specific alterations induced by eCG upon glandular and vascular characteristics of bovine uterus. To investigate the influence of eCG on: uterine thickness and area; uterine artery diameter and area; uterine vascular and gland density; and the expression of the VEGFA-system, the uteri of crossbred beef cows were collected. All cows were submitted to follicular wave emergence synchronization. On day four of protocol, cows submitted to superovulation (n = 6) received 2000 IU eCG, on day eight, after expected follicular deviation, cows submitted to stimulatory treatment (n = 5) received 400 IU eCG. Control cows (n = 5) did not receive eCG. On day five po cows were subjected to ultrassonographic evaluation and slaughtered for uterine tissue sampling on day six po. Uterine vessels and glands were quantified by the counting point stereological method. The VEGFA-system was localized in different cellular types, showing no qualitative or quantitative differences in the site of expression or the intensity of the positive signal among the groups. Vascular density was decreased in the endometrium of stimulated and myometrium of superovulated cows compared with the control ones, which showed higher vascular density in the myometrium and endometrium of the ipsilateral uterine horn. The uterine gland density was higher in superovulated compared with stimulated and control cows. Thus, we can infer that stimulatory or superovulatory treatments with eCG influence the vascular density in the endometrium and myometrium in cattle.
Assuntos
Bovinos/fisiologia , Gonadotropinas Equinas/administração & dosagem , Útero/anatomia & histologia , Útero/irrigação sanguínea , Animais , Endométrio/irrigação sanguínea , Endométrio/efeitos dos fármacos , Sincronização do Estro , Feminino , Expressão Gênica , Imuno-Histoquímica , Miométrio/irrigação sanguínea , Miométrio/efeitos dos fármacos , Indução da Ovulação , Gravidez , Superovulação , Ultrassonografia , Artéria Uterina/anatomia & histologia , Artéria Uterina/efeitos dos fármacos , Útero/diagnóstico por imagem , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
PURPOSE: The aim of this study was to evaluate the use of Doppler velocimetry of the uterine arteries and its association to endometrial thickness as a method to confirm pituitary suppression after administration of gonadotropin-releasing hormone analogues in assisted reproduction treatment cycles. METHODS: A total of 70 patients using gonadotropin-releasing hormone analogues for pituitary suppression for in vitro fertilization treatment were studied. To confirm down-regulation, serum estradiol levels and endometrial thickness were evaluated 10 days after gonadotropin-releasing hormone analogues administration. When estradiol was <30 pg/ml and endometrial thickness was <3 mm, pituitary suppression was confirmed. Doppler velocimetric measurements were performed at the same day to study the pulsatility index of the uterine arteries, until pituitary suppression was confirmed. RESULTS: All 70 patients had normal ovarian morphology. For the patients who had estradiol levels ≤30 pg/ml, the mean pulsatility index of the uterine arteries was 2.95 ± 0.79 and for those who had levels >30 pg/ml the mean PI was 2.22 ± 0.8 (p = 0.005). For the patients who had endometrial thickness ≤5 mm the mean PI was 2.86 ± 0.82 and for those with endometrial thickness >5 mm the mean PI was 2.17 ± 0.79 (p = 0.004). Using a cut-off point of 2.51 for the pulsatility index, to compare to estradiol levels, we observed a sensitivity of 72.7 % and specificity of 71 %. The combination of Doppler velocimetric and endometrial thickness showed a sensitivity of 94 % and specificity of 82.3 %. CONCLUSIONS: Doppler velocimetric analysis of the uterine arteries can be an important tool in the diagnosis of the down-regulation after the use of gonadotropin-releasing hormone analogues and might help simplify assisted reproduction programmes.
Assuntos
Monitoramento de Medicamentos/métodos , Endométrio/efeitos dos fármacos , Fármacos para a Fertilidade Feminina/farmacologia , Fertilização in vitro/métodos , Gosserrelina/farmacologia , Fluxometria por Laser-Doppler , Artéria Uterina/diagnóstico por imagem , Adulto , Biomarcadores/sangue , Regulação para Baixo , Esquema de Medicação , Endométrio/diagnóstico por imagem , Endométrio/fisiologia , Estradiol/sangue , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Gosserrelina/administração & dosagem , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Indução da Ovulação/métodos , Estudos Prospectivos , Fluxo Pulsátil/efeitos dos fármacos , Sensibilidade e Especificidade , Ultrassonografia , Artéria Uterina/efeitos dos fármacos , Artéria Uterina/fisiologiaRESUMO
OBJECTIVE: To evaluate Doppler velocimetry parameters (resistance index [RI], pulsatility index [PI] and systolic/diastolic [S/D] ratio) of maternal-fetal circulation before and after magnesium sulfate administration in pregnant women with severe preeclampsia. METHODS: A prospective observational cohort analysis of 40 women with severe preeclampsia was performed. Doppler ultrasonography scans were performed before and 20 minutes after intravenous administration of magnesium sulfate. Maternal parameters such as heart rate, and systolic, diastolic and mean arterial pressure were recorded. Doppler flow velocity parameters (RI, PI and S/D ratio) were evaluated in the uterine, umbilical and middle cerebral arteries. The different mean values obtained before and after magnesium sulphate were analyzed using the paired t-test. RESULTS: There was a statistically significant increase in mean maternal heart rate and a statistically significant decrease in systolic, diastolic and mean maternal blood pressure before and after administration of magnesium sulphate (p < 0.001). Resistance index decreased in the umbilical (p = 0.003; 95% CI: 0.008 - 0.03) and middle cerebral artery (p = 0.001; 95% CI: 0.01 - 0.05) and in both uterine arteries. Likewise, there was a significant reduction in the PI and S/D ratio in all the arteries assessed. CONCLUSIONS: Maternal administration of intravenous magnesium sulfate in preeclampsia leads to an increase in maternal heart rate and a decrease in systolic, diastolic and mean arterial blood pressure. A reduction in the resistance index, pulsatility index and S/D ratio was recorded in the uterine, umbilical and cerebral arteries.
Assuntos
Anticonvulsivantes/administração & dosagem , Sulfato de Magnésio/administração & dosagem , Pré-Eclâmpsia/tratamento farmacológico , Adolescente , Adulto , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Feminino , Humanos , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/efeitos dos fármacos , Pré-Eclâmpsia/diagnóstico por imagem , Pré-Eclâmpsia/fisiopatologia , Gravidez , Estudos Prospectivos , Ultrassonografia Pré-Natal , Artérias Umbilicais/diagnóstico por imagem , Artérias Umbilicais/efeitos dos fármacos , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVES: To evaluate Doppler velocimetry (resistance index (RI) and peak systolic velocity (PSV)) in the maternal-fetal circulation before and 5 and 24 h after tocolysis with oral nifedipine. METHODS: This was a prospective, observational, analytic cohort study performed in 47 pregnant women undergoing nifedipine tocolysis, each subject acting as her own control. Doppler assessment of uterine, umbilical and fetal middle cerebral (MCA) arteries was performed before and 5 and 24 h after an initial 20-mg sublingual dose, which was repeated twice at 20-min intervals if contractions failed to diminish. The maintenance dose consisted of 20 mg orally every 6 h for 24 h up to a total of 100-120 mg nifedipine. We analyzed whether there was a time effect and compared values at the different time-points. RESULTS: The MCA-RI had decreased significantly after 24 h of tocolysis (0 h = 0.85; 5 h = 0.85; 24 h = 0.81; P = 0.001), with no differences in uterine or umbilical arteries or in the MCA to umbilical artery ratio. The MCA-PSV had reduced significantly after 5 h (0 h = 41.5 cm/s; 5 h = 34.7 cm/s; P = 0.001), returning close to baseline levels between 5 and 24 h. The PSV increased significantly between 5 and 24 h in the right uterine artery (5 h = 55.1 cm/s; 24 h = 65.0 cm/s; P = 0.037) and in the umbilical artery (5 h = 28.4 cm/s; 24 h = 33.1 cm/s; P = 0.038). CONCLUSIONS: Nifedipine tocolysis is associated with a reduction in RI in the MCA but not in the uterine or umbilical arteries, a reduction in PSV in the MCA after 5 h but returning to baseline within 24 h, and an increase in PSV between 5 and 24 h in the umbilical and right uterine arteries.