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1.
Anim Reprod Sci ; 248: 107183, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36592521

RESUMO

The present study aimed to investigate the Doppler indices and mRNA transcripts of hormone receptors in relation to the response of dilatation therapy in incomplete cervical dilatation (ICD) associated with uterine torsion in buffaloes. Out of 36 successfully detorted uterine torsion cases, eight buffaloes revealed a fully dilated cervix, while the remaining 28 had ICD, and subjected to dilatation therapy (500 µg cloprostenol + 2 mg estradiol benzoate + 80 mg valethamate bromide + 50 IU oxytocin + 250 mL calcium borogluconate). The responses of dilatation therapy were assessed in 26 buffaloes as one died, and one could not follow up. Doppler indices of middle uterine arteries on trans-rectal ultrasound were evaluated pre- and 30-60 min post-detorsion. Cervical tissue biopsies were collected from 16 buffaloes to study mRNA transcripts of hormone receptors. The duration, degree, location of uterine torsion, fetal viability, consistency of the cervix, relaxation of pelvic ligaments, udder engorgement, and gestation length were also recorded to evaluate the response of dilatation therapy. The 73.08% (19/26) buffaloes responded to the therapy with a duration ranging from 2 to 56 hrs (18.41 ± 4.11). The significantly increased blood flow volume (BFV) and time-average peak velocity (TAP) while the significantly reduced resistive index (RI) and pulsatility index (PI) in an ipsilateral middle uterine artery (MUA) at post-detorsion were observed in dilation therapy responded than the not-responded group. The mRNA transcripts of estradiol receptors-α (ESR1), prostaglandin receptors (PTGFR), and oxytocin receptors (OXTR) were upregulated by 7.47, 6.63, and 8.72-fold in the ICD group, respectively. The Doppler indices along with duration of illness, location of uterine torsion, consistency of the cervix, and udder engorgement can be used to predict the response of dilatation therapy in ICD associated with uterine torsion. The upregulated mRNA expression of ESR1, PTGFR and OXTR is mandatory for success of dilatation therapy.


Assuntos
Búfalos , Colo do Útero , Animais , Feminino , Búfalos/fisiologia , Colo do Útero/diagnóstico por imagem , Dilatação/veterinária , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/fisiologia , Útero/irrigação sanguínea
2.
J Mol Endocrinol ; 70(2)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36476832

RESUMO

Elevated endogenous estrogens stimulate human uterine artery endothelial cell (hUAEC) hydrogen sulfide (H2S) production by selectively upregulating the expression of H2S synthesizing enzyme cystathionine ß-synthase (CBS), but the underlying mechanisms are underdetermined. We hypothesized that CBS transcription mediates estrogen-stimulated pregnancy-dependent hUAEC H2S production. Estradiol-17ß (E2ß) stimulated CBS but not cystathionine γ-lyase (CSE) expression in pregnant human uterine artery ex vivo, which was attenuated by the estrogen receptor (ER) antagonist ICI 182,780. E2ß stimulated CBS mRNA/protein and H2S production in primary hUAEC from nonpregnant and pregnant women, but with greater responses in pregnant state; all were blocked by ICI 182,780. Human CBS promoter contains multiple estrogen-responsive elements (EREs), including one ERE preferentially binding ERα (αERE) and three EREs preferentially binding ERß (ßERE), and one full ERE (α/ßERE) and one half ERE (½α/ßERE) binding both ERα and ERß. Luciferase assays using reporter genes driven by human CBS promoter with a series of 5'-deletions identified the α/ßEREs binding both ERα and ERß (α/ßERE and ½α/ßERE) to be important for baseline and E2ß-stimulated CBS promoter activation. E2ß stimulated ERα/ERß heterodimerization by recruiting ERα to α/ßEREs and ßERE, and ERß to ßERE, α/ßEREs, and αERE. ERα or ERß agonist alone trans-activated CBS promoter, stimulated CBS mRNA/protein and H2S production to levels comparable to that of E2ß-stimulated, while ERα or ERß antagonist alone abrogated E2ß-stimulated responses. E2ß did not change human CSE promoter activity and CSE mRNA/protein in hUAEC. Altogether, estrogen-stimulated pregnancy-dependent hUAEC H2S production occurs by selectively upregulating CBS expression via ERα/ERß-directed gene transcription.


Assuntos
Receptor beta de Estrogênio , Receptores de Estrogênio , Feminino , Gravidez , Humanos , Receptores de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Cistationina beta-Sintase/genética , Cistationina beta-Sintase/metabolismo , Fulvestranto/metabolismo , Artéria Uterina/metabolismo , Estrogênios/farmacologia , Estrogênios/metabolismo , Estradiol/farmacologia , Estradiol/metabolismo , Células Endoteliais/metabolismo , RNA Mensageiro/genética
4.
Sci Rep ; 12(1): 20913, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463315

RESUMO

To determine whether a history of previous Cesarean delivery (CD) impacts uterine artery (UtA) Doppler indices throughout pregnancy. Women with and without CD (NCD) were prospectively enrolled for sequential assessments of the UtA mean/median pulsatility index (UtA-PI), resistance index (UtA-RI), and systolic/diastolic ratio (UtA-S/D) at 11-13 + 6, 14-19 + 6, 30-34 + 6, and 35-37 + 6 weeks' gestation. Data from 269/269, 246/257, 237/254, and 219/242 CD/NCD participants from each gestational period were available for analysis. Multiples of the median (MoMs) of UtA Doppler indices showed biphasic temporal (Δ) pattern; with an initial dropping until the second trimester, then a subsequent elevation until late in pregnancy (p < 0.05). The measurements and Δs of the UtA indices between CD and NCD were not different (p > 0.05). Mixed-effects modelling ruled out effects from nulliparity (n = 0 and 167 for CD and NCD, respectively) (p > 0.05). History of CD neither influenced the measurements nor the temporal changes of the UtA Doppler indices throughout pregnancy. The biphasic Δs of UtA Doppler indices added to the longitudinal data pool, and may aid in future development of a more personalized prediction using sequential/contingent methodologies, which may reduce the false results from the current cross-sectional screening.


Assuntos
Doenças não Transmissíveis , Artéria Uterina , Gravidez , Feminino , Humanos , Artéria Uterina/diagnóstico por imagem , Estudos Prospectivos , Estudos de Casos e Controles , Estudos Transversais
5.
Physiol Rep ; 10(23): e15518, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36461654

RESUMO

Intrauterine growth restriction (IUGR) and exposure to a high-fat diet (HFD) independently increase the risk of cardiovascular disease (CVD) and hyperlipidemia. In our previous studies, IUGR increased blood pressure and promoted vascular remodeling and stiffness in early life, a finding that persisted and was augmented by a maternal HFD through postnatal day (PND) 60. The impact of these findings with aging and the development of hyperlipidemia and atherosclerosis remain unknown. We hypothesized that the previously noted impact of IUGR on hypertension, vascular remodeling, and hyperlipidemia would persist. Adult female rats were fed either a regular diet (RD) or high fat diet (HFD) prior to conception through lactation. IUGR was induced by uterine artery ligation. Offspring were weaned to either RD or HFD through PND 365. For both control (C) and IUGR (I) and rats, this resulted in the following six groups per sex: offspring from RD dams weaned to an RD (CRR and IRR), or offspring from HFD dams weaned to either an RD (CHR and IHR) or to an HFD (CHH and IHH). IHH male and female rats had increased large artery stiffness, a suggestion of fatty streaks in the aorta, and persistent decreased elastin and increased collagen in the aorta and carotid arteries. Post-weaning HFD intake increased blood lipids regardless of IUGR status. IUGR increased HFD-induced mortality. We speculate that HFD-induced risk of CVD and mortality is potentiated by developmental programming of the ECM.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Feminino , Masculino , Ratos , Animais , Humanos , Retardo do Crescimento Fetal/etiologia , Dieta Hiperlipídica/efeitos adversos , Remodelação Vascular , Artéria Uterina , Aterosclerose/etiologia
6.
BMJ Case Rep ; 15(12)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564091

RESUMO

A woman in early 20s with type 1 von Willebrand disease (vWD) presented to the emergency department with abdominal pain and vaginal bleeding at 5 weeks post partum following primary caesarean section. Imaging revealed a uterine artery pseudoaneurysm (UAP), which is a rare condition that can cause postpartum haemorrhage. Caesarean birth and vWD are two risk factors for pseudoaneurysm. Swift postpartum recognition of a pseudoaneurysm is essential to prevent a potentially life-threatening outcome. Successful diagnosis and treatment of the patient's symptoms required interdisciplinary teamwork between obstetricians, interventional radiologists and haematologists. Uterine artery embolisation (UAE) was performed and complete resolution of the pseudoaneurysm was noted 6 weeks after the procedure. Haemorrhage was averted due to early detection of UAP prior to its rupture, and future fertility was preserved. The patient successfully conceived a second child 1 year after UAE and delivered via caesarean birth without haemorrhage or recurrence of UAP.


Assuntos
Falso Aneurisma , Hemorragia Pós-Parto , Embolização da Artéria Uterina , Doenças de von Willebrand , Feminino , Humanos , Gravidez , Falso Aneurisma/complicações , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/terapia , Cesárea/efeitos adversos , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/terapia , Período Pós-Parto , Artéria Uterina/diagnóstico por imagem , Embolização da Artéria Uterina/métodos , Doenças de von Willebrand/complicações , Doenças de von Willebrand/terapia
7.
Kidney360 ; 3(10): 1785-1794, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36514732

RESUMO

Preeclampsia (PE), new-onset hypertension during pregnancy, affects up to 10% of pregnancies worldwide. Despite being the leading cause of maternal and fetal morbidity and mortality, PE has no cure beyond the delivery of the fetal-placental unit. Although the exact pathogenesis of PE is unclear, there is a strong correlation between chronic immune activation; intrauterine growth restriction; uterine artery resistance; dysregulation of the renin-angiotensin system. Which contributes to renal dysfunction; and the resulting hypertension during pregnancy. The genesis of PE is thought to begin with insufficient trophoblast invasion leading to reduced spiral artery remodeling, resulting in decreased placental perfusion and thereby causing placental ischemia. The ischemic placenta releases factors that shower the endothelium and contribute to peripheral vasoconstriction and chronic immune activation and oxidative stress. Studies have shown imbalances in proinflammatory and anti-inflammatory cell types in women with PE and in animal models used to examine mediators of a PE phenotype during pregnancy. T cells, B cells, and natural killer cells have all emerged as potential mediators contributing to the production of vasoactive factors, renal and endothelial dysfunction, mitochondrial dysfunction, and hypertension during pregnancy. The chronic immune activation seen in PE leads to a higher risk for other diseases, such as cardiovascular disease, CKD, dementia during the postpartum period, and PE during a subsequent pregnancy. The purpose of this review is to highlight studies demonstrating the role that different lymphoid cell populations play in the pathophysiology of PE. Moreover, we will discuss treatments focused on restoring immune balance or targeting specific immune mediators that may be potential strategies to improve maternal and fetal outcomes associated with PE.


Assuntos
Hipertensão , Pré-Eclâmpsia , Humanos , Animais , Feminino , Gravidez , Pré-Eclâmpsia/genética , Placenta/irrigação sanguínea , Artéria Uterina/metabolismo , Isquemia , Células Matadoras Naturais/metabolismo
8.
Redox Biol ; 58: 102555, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36446230

RESUMO

The proteomic analysis from samples of patients with preeclampsia (PE) displayed a low level of ferritin light chains (FTL), but we do not know what the significance of reduced FTL in PE pathophysiology is. To address this question, we first demonstrated that FTL was expressed in first- and third-trimester cytotrophoblasts, including extravillous trophoblasts (EVTs), of the human placenta. Furthermore, a pregnant rat model of FTL knockdown was successfully established by intravenously injecting adenoviruses expressing shRNA targeting FTL. In pregnant rats with downregulated FTL, we observed PE-like phenotypes and impaired spiral arterial remodelling, implying a causal relationship between FTL downregulation and PE. Blocking ferroptosis with ferrostatin-1 (Fer-1) significantly rescued the above PE-like phenotypes in pregnant rats with FTL knockdown. Furthermore, using trophoblast cell line and chorionic villous explant culture assays, we showed that FTL downregulation induced cell death, especially ferroptosis, resulting in defective uterine spiral artery remodelling. Eventually, this conclusion from the animal model was verified in PE patients' placental tissues. Taken together, this study revealed for the first time that FTL reduction during pregnancy triggered ferroptosis and then caused defective uterine spiral artery remodelling, thereby leading to PE.


Assuntos
Ferroptose , Pré-Eclâmpsia , Humanos , Gravidez , Feminino , Ratos , Animais , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Apoferritinas/metabolismo , Placenta/metabolismo , Proteômica , Artérias/metabolismo , Artéria Uterina/metabolismo
9.
Afr Health Sci ; 22(2): 690-694, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36407372

RESUMO

Background: The proximity of the uterus and the cervix to the urinary tract predisposes the latter to injury during obstetrical and gynaecological surgical procedures. Following a difficult surgical procedure on the lower uterine segment and or adnexa, urinary tract injury should be excluded. Methods: A booked 39-year-old G3P2 lady who suffered an ischaemic stroke in the index pregnancy had a caesarean delivery at 39 weeks of gestation and sustained an extensive tear that extended inferiorly on the left lateral aspect of the uterus and this resulted in postpartum haemorrhage. Following the repair of the tear, uterine artery ligation was performed to achieve haemostasis. Results: Postoperatively, conventional ultrasonography which was performed to exclude ureteric injury suggested left hydronephrosis and a preliminary report of computerized tomography (CT) showed the same finding. The patient subsequently had left ureteric stenting. The final report of the CT scan was delayed but showed a simple left renal cyst and no hydronephrosis. Conclusion: Renal cyst is a differential diagnosis of hydronephrosis. Delayed availability of the final result of medical investigations jeopardises patients' safety. A preliminary imaging report is prone to error and its use to determine the indication for an invasive procedure should be limited to emergencies.


Assuntos
Isquemia Encefálica , Doenças Renais Císticas , Neoplasias Renais , Hemorragia Pós-Parto , Acidente Vascular Cerebral , Humanos , Gravidez , Feminino , Adulto , Hemorragia Pós-Parto/diagnóstico , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/cirurgia , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/cirurgia , Útero
10.
Bull Exp Biol Med ; 173(6): 787-789, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36322311

RESUMO

Biomicroscopy was used to study order I-IV branches of the uterine artery in sexually mature female Wistar rats after a single 5- or 10-min direct exposure of the right broad ligament of the uterus to a helium-neon laser beam in the red band of the spectrum (λ=632.8 nm, output power 2 mW, intensity 20 mW/cm2). Under the influence of laser exposure, there was a significant increase in the diameter of small uterine branches and a weaker increase in large vessels with a well-developed muscular membrane. Preliminary administration of zinc IX protoporphyrin hemoxygenase blocker (30 mmol/kg) reduced reactivity of the vascular bed to laser irradiation, mainly of order I-II branches. It was concluded that carbon monoxide can act as an intermediary between the laser exposure and uterine vessels.


Assuntos
Monóxido de Carbono , Artéria Uterina , Ratos , Feminino , Animais , Neônio , Hélio , Ratos Wistar , Lasers
11.
Pregnancy Hypertens ; 30: 154-160, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36270137

RESUMO

OBJECTIVE: To evaluate the role of angiogenic biomarkers in predicting severe adverse materno-fetal outcome (SAO) among women at high risk of preeclampsia (PE). METHOD: All antenatal women at high risk of PE underwent MAP estimation, sFlt-1/PlGF ratio, uterine artery evaluation at 20-22, 28-30 and 34-36 weeks of gestation and were followed until delivery. The severe adverse outcome included severe PE, severe fetal growth restriction with Doppler changes and intrauterine death or early neonatal death. Those who developed SAO were cases and rest were controls, the cases and controls were compared using univariate and multivariate logistic regression analysis. RESULTS: In 54/287(18.8 %) SAO was observed, and they comprised of severe PE (21/287, 7.3 %), FGR with absent or reverse diastolic flow on Doppler (23/287, 8.0 %) and intrauterine death or early neonatal death (10/287, 3.5 %). For detecting complications up to 30 weeks, the sFLT-1/PlGF ratio at 20 weeks (cut off ≥ 38) was the best test (accuracy- 97.6 %) followed by MAP and uterine artery Doppler PI. For detecting complications up to 34 weeks, prediction was good (accuracy -80.4 %) when sFLT-1/PlGF ratio was combined with uterine artery PI. The predictive value of the complications before 34 weeks was far superior to that after 34 weeks. Combining the sFLT-1/PlGF ratio with the uterine artery PI improved the accuracy of the test (79 % to 87 %). CONCLUSION: Increased sFlt-1/PlGF ratio, was a good predictive marker for SAO in the study population. The accuracy of prediction was better for those who developed the complications before 34 weeks.


Assuntos
Morte Perinatal , Pré-Eclâmpsia , Recém-Nascido , Feminino , Humanos , Gravidez , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Pré-Eclâmpsia/diagnóstico , Valor Preditivo dos Testes , Fator de Crescimento Placentário , Artéria Uterina/diagnóstico por imagem , Natimorto , Biomarcadores
12.
PLoS One ; 17(10): e0275129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36260615

RESUMO

INTRODUCTION: This trial evaluates whether daily low-dose aspirin initiated before 16 weeks of gestation can reduce preeclampsia and fetal growth restriction in nulliparous women identified by first-trimester uterine artery Dopplers as at high risk of preeclampsia. METHODS: This randomized, blinded, placebo-controlled, parallel-group trial took place in 17 French obstetric departments providing antenatal care. Pregnant nulliparous women aged ≥ 18 years with a singleton pregnancy at a gestational age < 16 weeks of gestation with a lowest pulsatility index ≥ 1.7 or a bilateral protodiastolic notching for both uterine arteries on an ultrasound performed between 11+0 and 13+6 weeks by a certified sonographer were randomized at a 1:1 ratio to 160 mg of low-dose aspirin or to placebo to be taken daily from inclusion to their 34th week of gestation. The main outcome was preeclampsia or a birthweight ≤ 5th percentile. Other outcomes included preeclampsia, severe preeclampsia, preterm preeclampsia, preterm delivery before 34 weeks, mode of delivery, type of anesthesia, birthweight ≤ 5th percentile and perinatal death. RESULTS: The trial was interrupted due to recruiting difficulties. Between June 2012 and June 2016, 1104 women were randomized, two withdrew consent, and two had terminations of pregnancies. Preeclampsia or a birthweight ≤ 5th percentile occurred in 88 (16.0%) women in the low-dose aspirin group and in 79 (14.4%) in the placebo group (proportion difference 1.6 [-2.6; 5.9] p = 0.45). The two groups did not differ significantly for the secondary outcomes. CONCLUSION: Low-dose aspirin was not associated with a lower rate of either preeclampsia or birthweight ≤ 5th percentile in women identified by their first-trimester uterine artery Doppler as at high risk of preeclampsia. TRIAL REGISTRATION: (NCT0172946).


Assuntos
Pré-Eclâmpsia , Artéria Uterina , Recém-Nascido , Feminino , Gravidez , Humanos , Masculino , Artéria Uterina/diagnóstico por imagem , Pré-Eclâmpsia/prevenção & controle , Pré-Eclâmpsia/tratamento farmacológico , Peso ao Nascer , Aspirina/uso terapêutico , Primeiro Trimestre da Gravidez
13.
J Gynecol Obstet Hum Reprod ; 51(9): 102465, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36055633

RESUMO

BACKGROUND AND OBJECTIVES: Lateral occlusion prior to TLH has been suggested to reduce perioperative bleeding, operative time, and hospital stay. Furthermore, reducing the amount of bleeding and the length of the operation may affect parameters such as postoperative pain and the number of patients with postoperative vaginal vault hematoma. METHODS: This RCT was conducted at a single center at Odense University Hospital in Denmark. Between February 2016 and February 2019, a total of 58 patients undergoing TLH and bilateral salpingectomy for benign cases were recruited to the study. RESULTS: The mean operating time was significantly longer in the LA group with a mean difference between the two groups of six minutes. No other discrepancy regarding the primary outcomes was observed between the two groups. Total blood loss was similar in the two groups as well as the average hospital stay and the VAS score during the first seven days. 93% of the patients were discharged from the hospital within the first 24 h postoperatively. CONCLUSION: This RCT demonstrates that lateral occlusion of the uterine artery prior to TLH does not improve outcome for the patients and should therefore not be used as a standard procedure.


Assuntos
Histerectomia Vaginal , Laparoscopia , Feminino , Humanos , Histerectomia Vaginal/métodos , Artéria Uterina/cirurgia , Laparoscopia/métodos , Histerectomia/métodos , Duração da Cirurgia
14.
Am J Physiol Regul Integr Comp Physiol ; 323(5): R670-R681, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36121142

RESUMO

Placenta ischemia, the initiating event in preeclampsia (PE), is associated with fetal growth restriction. Inhibition of the agonistic autoantibody against the angiotensin type 1 receptor AT1-AA, using an epitope-binding inhibitory peptide ('n7AAc') attenuates increased blood pressure at gestational day (G)19 in the clinically relevant reduced uterine perfusion pressure (RUPP) model of PE. Thus we tested the hypothesis that maternal administration of 'n7AAc' does not transfer to the fetus, improves uterine blood flow and fetal growth, and attenuates elevated placental expression of miRNAs implicated in PE and FGR. Sham or RUPP surgery was performed at G14 with vehicle or 'n7AAc' (144 µg/day) administered via an osmotic pump from G14 to G20. Maternal plasma levels of the peptide on G20 were 16.28 ± 4.4 nM, and fetal plasma levels were significantly lower at 1.15 ± 1.7 nM (P = 0.0007). The uterine artery resistance index was significantly elevated in RUPP (P < 0.0001) but was not increased in 'n7AAc'-RUPP or 'n7AAc'-Sham versus Sham. A significant reduction in fetal weight at G20 in RUPP (P = 0.003) was not observed in 'n7AAc'-RUPP. Yet, percent survival was reduced in RUPP (P = 0.0007) and 'n7AAc'-RUPP (P < 0.0002). Correlation analysis indicated the reduction in percent survival during gestation was specific to the RUPP (r = 0.5342, P = 0.043) and independent of 'n7AAc'. Placental miR-155 (P = 0.0091) and miR-181a (P = 0.0384) expression was upregulated in RUPP at G20 but was not elevated in 'n7AAc'-RUPP. Collectively, our results suggest that maternal administration of 'n7AAc' does not alter fetal growth in the RUPP implicating its potential as a therapeutic for the treatment of PE.NEW & NOTEWORTHY The seven amino acid inhibitory peptide to the AT1-AA ('n7AAc') has limited transfer to the fetus at gestational day 20, improves uterine blood flow and fetal growth in the reduced uterine perfusion pressure model of preeclampsia (PE), and does not impair fetal survival during gestation in sham-operated or placental ischemic rats. Collectively, these findings suggest that maternal administration of 'n7AAc' as an effective strategy for the treatment of PE is associated with improved outcomes in the fetus.


Assuntos
MicroRNAs , Pré-Eclâmpsia , Animais , Feminino , Humanos , Gravidez , Ratos , Aminoácidos/metabolismo , Autoanticorpos/metabolismo , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Epitopos/metabolismo , Desenvolvimento Fetal , Isquemia , MicroRNAs/metabolismo , Peptídeos/farmacologia , Placenta/metabolismo , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Artéria Uterina
15.
J Biomech Eng ; 144(12)2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36128759

RESUMO

Hypertensive pregnancy disorders (HPDs), such as pre-eclampsia, are leading sources of both maternal and fetal morbidity in pregnancy. Noninvasive imaging, such as ultrasound (US) and magnetic resonance imaging (MRI), is an important tool for predicting and monitoring these high risk pregnancies. While imaging can measure hemodynamic parameters, such as uterine artery pulsatility and resistivity indices (PI and RI), the interpretation of such metrics for disease assessment relies on ad hoc standards, which provide limited insight to the physical mechanisms underlying the emergence of hypertensive pregnancy disorders. To provide meaningful interpretation of measured hemodynamic data in patients, advances in computational fluid dynamics can be brought to bear. In this work, we develop a patient-specific computational framework that combines Bayesian inference with a reduced-order fluid dynamics model to infer parameters, such as vascular resistance, compliance, and vessel cross-sectional area, known to be related to the development of hypertension. The proposed framework enables the prediction of hemodynamic quantities of interest, such as pressure and velocity, directly from sparse and noisy MRI measurements. We illustrate the effectiveness of this approach in two systemic arterial network geometries: an aorta with branching carotid artery and a maternal pelvic arterial network. For both cases, the model can reconstruct the provided measurements and infer parameters of interest. In the case of the maternal pelvic arteries, the model can make a distinction between the pregnancies destined to develop hypertension and those that remain normotensive, expressed through the value range of the predicted absolute pressure.


Assuntos
Hipertensão , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Estudos de Viabilidade , Teorema de Bayes , Artéria Uterina/diagnóstico por imagem , Pré-Eclâmpsia/diagnóstico por imagem , Hipertensão/diagnóstico por imagem , Fluxo Pulsátil
16.
Am J Physiol Regul Integr Comp Physiol ; 323(5): R694-R699, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36094446

RESUMO

In healthy near-term women, blood flow to the uteroplacental circulation is estimated as 841 mL/min, which is greater than in other mammalian species. We argue that as uterine venous Po2 sets the upper limit for O2 diffusion to the fetus, high uterine artery blood flow serves to narrow the maternal arterial-to-uterine venous Po2 gradient and thereby raise uterine vein Po2. In support, we show that the reported levels for uterine artery blood flow agree with what is required to maintain normal fetal growth. Although residence at high altitudes (>2,500 m) depresses fetal growth, not all populations are equally affected; Tibetans and Andeans have higher levels of uterine artery blood flow than newcomers and exhibit normal fetal growth. Estimates of uterine venous Po2 from the umbilical blood-gas data available from healthy Andean pregnancies indicate that their high levels of uterine artery blood flow are consistent with their reported, normal birth weights. Unknown, however, are the effects on placental gas exchange of the lower levels of uterine artery blood flow seen in high-altitude newcomers or hypoxia-associated pregnancy complications. We speculate that, by widening the maternal artery to uterine vein Po2 gradient, lower levels of uterine artery blood flow prompt metabolic changes that slow fetal growth to match O2 supply.


Assuntos
Placenta , Circulação Placentária , Animais , Humanos , Gravidez , Feminino , Placenta/metabolismo , Artéria Uterina/metabolismo , Oxigênio , Desenvolvimento Fetal/fisiologia , Mamíferos/metabolismo
18.
Reprod Domest Anim ; 57(12): 1554-1563, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36005750

RESUMO

We investigated the structural features of arterial blood vessels in yak uterine caruncle and the effects of the expression of vascular regulation-related factors on angiogenesis in pregnant and non-pregnant yak uterus. Three-dimensional specimens of the uterine artery of non-pregnant and pregnant yaks were produced to observe and measure the distribution characteristics and number of arterial vessels in the uterus and caruncle in the two periods. The uterine caruncle structure was observed and analysed by haematoxylin-eosin staining. The expression features of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) in the uterine caruncle were detected with immunohistochemistry, quantitative real-time PCR (qRT-PCR) and western blotting. The length and number of blood vessels in the caruncle were increased, the degree of curvature was decreased, and the folding was more complicated during pregnancy as compared with that during non-pregnancy. The immunohistochemical results demonstrated that VEGF and Ang-1 were mainly expressed strongly in the mucosal epithelial cytoplasm. The glandular lumen of the uterine gland, lymphocytes and the media and adventitia of blood vessels are widely distributed, and they are all positive. VEGF and Ang-1 mRNA and protein levels were highest in pregnancy, followed by that in the luteal phase and in the follicular phase, and three stages were significantly different (p < .05). These findings provide an anatomical reference and theoretical basis for improving the diagnosis and treatment of yak reproductive disorders and other diseases in high-altitude and low-oxygen environments.


Assuntos
Angiopoietina-1 , Fator A de Crescimento do Endotélio Vascular , Feminino , Bovinos , Animais , Angiopoietina-1/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Útero/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Artéria Uterina
19.
J Equine Vet Sci ; 118: 104107, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36002117

RESUMO

The aim of this double-blinded placebo-controlled study was to investigate the effect of acetylsalicylic acid (ASA) on uterine blood flow, gestation length, placental and foal weights in pregnant mares. Sixteen Thoroughbred mares of different age (13.3 ± 4.1) and parity (7.4 ± 3.1) were randomly assigned to three treatment groups. Mares in group C (n = 4) served as controls and received 5,000 mg lactose orally once daily from D 120 (D 0 = day of ovulation) until parturition. Mares in group ASA1 (n = 7) received 5,000 mg ASA orally once daily from D 120 until parturition. Mares in group ASA2 (n = 5) received the same dose ASA as group ASA1 from D 120 to D 285, but twice daily from D 285 until parturition. Mares were examined by ultrasonography on D 14, 28, and 60, and in 21-days intervals from D 120 until parturition. The cross-sectional area, time average maximum velocity (TAMV), and pulsatility index were measured in both uterine arteries and the blood flow volume was calculated for each uterine artery and then summarized. All 16 mares carried a normal pregnancy and delivered live foals. In group ASA2 TAMV in the ipsilateral artery was significantly higher (P = .03) and these mares showed a tendency of increased total blood flow volume (P = .07) during late pregnancy (D 305-346). Results indicate that oral administration of 5,000 mg of ASA twice daily in pregnant mares causes a rise in uterine blood flow during late pregnancy.


Assuntos
Circulação Placentária , Útero , Cavalos , Gravidez , Animais , Feminino , Peso ao Nascer , Útero/diagnóstico por imagem , Projetos Piloto , Aspirina/farmacologia , Placenta , Artéria Uterina/diagnóstico por imagem , Parto
20.
Int J Mol Sci ; 23(16)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36012456

RESUMO

Advanced maternal age (≥35 years) is associated with pregnancy complications. Aging impairs vascular reactivity and increases vascular stiffness. We hypothesized that uterine artery adaptations to pregnancy are impaired with advanced age. Uterine arteries of nonpregnant and pregnant (gestational day 20) young (4 months) and aged (9 months; ~35 years in humans) Sprague-Dawley rats were isolated. Functional (myogenic tone, n = 6-10/group) and mechanical (circumferential stress-strain, n = 10-24/group) properties were assessed using pressure myography and further assessment of elastin and collagen (histology, n = 4-6/group), and matrix metalloproteinase-2 (MMP-2, zymography, n = 6/group). Aged dams had worse pregnancy outcomes, including smaller litters and fetal weights (both p < 0.0001). Only in arteries of pregnant young dams did higher pressures (>100 mmHg) cause forced vasodilation. Across the whole pressure range (4-160 mmHg), myogenic behavior was enhanced in aged vs. young pregnant dams (p = 0.0010). Circumferential stress and strain increased with pregnancy in young and aged dams (p < 0.0001), but strain remained lower in aged vs. young dams (p < 0.05). Arteries from young nonpregnant rats had greater collagen:elastin ratios than the other groups (p < 0.05). In aged rats only, pregnancy increased MMP-2 active capacity. Altered functional and structural vascular adaptations to pregnancy may impair fetal growth and development with advanced maternal age.


Assuntos
Metaloproteinase 2 da Matriz , Artéria Uterina , Animais , Colágeno , Elastina , Feminino , Humanos , Idade Materna , Gravidez , Ratos , Ratos Sprague-Dawley
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