Uterine Artery Diameter Research Articles

Maternal AMPK pathway activation with uterine artery blood flow and fetal growth maintenance during hypoxia.

High-altitude (HA) hypoxia lowers uterine artery (UtA) blood flow during pregnancy and birth weight. Adenosine monophosphate kinase (AMPK) activation has selective, uteroplacental vasodilator effects that lessen hypoxia-associated birth weight reductions. In this study, we determined the relationship between AMPK-pathway gene expression and metabolites in the maternal circulation during HA pregnancy as well as with the maintenance of UtA blood flow and birth weight at HA. Residents at HA (2,793 m) versus low altitude (LA; 1,640 m) had smaller UtA diameters at weeks 20 and 34, lower UtA blood flow at week 20, and lower birth weight babies. At week 34, women residing at HA versus women residing at LA had decreased expression of upstream and downstream AMPK-pathway genes. Expression of the α1-AMPK catalytic subunit, PRKAA1, correlated positively with UtA diameter and blood flow at weeks 20 (HA) and 34 (LA). Downstream AMPK-pathway gene expression positively correlated with week 20 fetal biometry at both altitudes and with UtA diameter and birth weight at LA. Reduced gene expression of AMPK activators and downstream targets in women residing at HA versus women residing at LA, together with positive correlations between PRKAA1 gene expression, UtA diameter, and blood flow suggest that greater sensitivity to AMPK activation at midgestation at HA may help offset later depressant effects of hypoxia on fetal growth.NEW & NOTEWORTHY Fetal growth restriction (FGR) is increased and uterine artery (UtA) blood flow is lower at high altitudes (HA) but not all HA pregnancies have FGR. Here we show that greater UtA diameter and blood flow at week 20 are positively correlated with higher expression of the gene encoding the α1-catalytic subunit of AMP protein kinase, PRKAA1, suggesting that increased AMPK activation may help to prevent the detrimental effects of chronic hypoxia on fetal growth.

284 Supranutritional Mineral Supplementation During Pregnancy Alters Placental Blood Flow and Calf Mineral Concentrations

Abstract Fetal development is dependent on maternal nutrient status, and the maternal-fetal connection is mediated by the placenta. There are well-established nutrient requirements for gestating cattle aimed at promoting the health of dam and fetus; however, there is limited information on the impact of supranutritional nutrient availability on placental function and calf development. This study evaluated the effect of supranutritional mineral administration during gestation on uterine artery blood flow and calf mineral status. Angus and SimAngus cows (n = 52) were bred via artificial insemination. At d 60 of gestation, cows were assigned to treatment groups; an injectable group (INJ, n = 26) receiving a single subcutaneous mineral injection and access to free-choice trace minerals and a control group (CON; n = 26) having access to free-choice trace minerals. Liver mineral content was analyzed in a subset of cows (CON n = 10; INJ n = 6) at d 60 and 209 ± 1 of gestation. At d 139.5 ± 0.5 and 209 ±1 of gestation, uterine artery measurements were collected using Color Doppler ultrasonography. Placental cotyledons, liver tissue, and blood samples were collected from a subset of animals at calving (n = 11; CON, n = 5; INJ, n = 6). Analysis revealed a TRT*day interaction at d 139.5 ± 0.5 for circulating Co concentrations which were greater (P = 0.05) and Se tended to be greater in INJ cows (P = 0.09) compared with CON cows. Circulating Zn concentrations tended to be decreased at d 209 ± 1 (P = 0.06) in INJ cows compared with the CON cows. Circulating Cu tended to be increased (P = 0.09) and Mn was decreased (P = 0.04) in INJ cows throughout the study. Hepatic Fe concentrations were decreased in INJ cows (P = 0.01) at d 209 ± 1. At d 139.5 ± 0.5, non-gravid uterine artery area, diameter, and circumference were increased in the INJ cows (P < 0.006 ). Additionally, pulsatility index of the gravid uterine artery tended to be increased (P = 0.09) in the INJ cows. Blood and liver samples were collected from calves (CON n = 24; INJ n = 26) at 4 to 8 d post-calving to assess mineral concentrations. INJ calves had greater liver Se (P = 0.001), decreased Fe (P = 0.04), and tended to have increased Zn (P = 0.09) and Mn (P = 0.08) concentrations compared with CON calves. Finally, INJ calves tended to have greater serum Se concentrations (P = 0.09) compared with CON calves. Trace minerals have roles in immune function and impact overall calf health. These results indicate that supranutritional trace mineral administration during early gestation alters placental blood flow and improves calf mineral availability. This supplementation protocol may provide the opportunity to improve the health of future calf crops.

Pathological features of early pregnancy disorders in women living at high altitude in KSA

ObjectivesPregnancy at high altitudes is relatively challenging because of hypobaric hypoxia, which is associated with a smaller uterine artery diameter and diminished blood flow. Here, we investigated the histopathological characteristics of early pregnancy disorders among pregnant women living in a high-altitude region (approximately 2200 m above sea level). MethodsThis cross-sectional study used retrospective data collection from a single tertiary hospital in a high-altitude region in KSA. Age and histopathology were analyzed in 495 women diagnosed with early pregnancy disorders (mainly miscarriage) in 2018–2020. ResultsApproximately one-fifth of pregnancies in this high-altitude region were lost before 24 weeks’ gestation, whereas 1150/6044 experienced miscarriage; 495 samples from those participants were sent for histopathological analysis. A total of 269 (54.34%) patients were younger than 35 years. Missed miscarriages accounted for 49.3% of miscarriages, followed by inevitable miscarriages (34.2%), which had a relatively higher frequency among mothers older than 35 years. The correlation between age and inevitable miscarriage was significant; ectopic pregnancy was diagnosed in 6.8%, molar pregnancy was detected in 6.26%, and blighted ovum was observed in 3.4%. ConclusionThe miscarriage rate in this high-altitude region was 19% of all pregnancies. Approximately half of the affected women were in their 30s. Missed miscarriage cases were relatively high in this region. The percentage of molar pregnancy was higher than those reported in prior studies, thus suggesting a need for monitoring and genetic workup practices. Furthermore, studies involving a larger population at high altitudes will be crucial for further risk assessment in addition to national studies on women living at sea level.

Risk Factors Associated with Clinical Failure of Uterine Artery Embolization for Postpartum Hemorrhage

PurposeTo identify risk factors for clinical failure of uterine artery embolization (UAE) for postpartum hemorrhage (PPH), with particular attention to the uterine artery diameter. Materials and MethodsThis retrospective study included 47 patients who underwent UAE for PPH between January 1, 2010, and January 31, 2021. Technical success was defined as the completion of embolization of the arteries thought to be the cause of the bleeding. Clinical success was defined as no recurrent bleeding or need for additional therapeutic interventions. Univariate and multivariate analyses were performed to examine the risk factors associated with clinical failure of UAE. ResultsOf the 47 patients, 6 had recurrent bleeding. Of the 6 patients, 4 underwent hysterectomy, and 2 underwent repeat embolization. The clinical success rate was 87.2% (41/47), with no major adverse events such as uterine infarction or death. In univariate analysis, there were slight differences in multiparity (P = .115) and placental abruption (P = .128) and a significant difference in the findings of a narrow uterine artery on digital subtraction angiography (DSA) (P = .005). In multivariate analysis, only a narrow uterine artery on DSA was a significant factor (odds ratio, 18.5; 95% confidence interval, 2.5–134.8; P = .004). ConclusionsA narrow uterine artery on DSA was a risk factor for clinically unsuccessful UAE for PPH. It may be prudent to conclude the procedure only after it is ensured that vasospasm has been relieved.

Blood vessel assessment using computed tomography : Effects of ephedrine on uterine artery.

Background: Ephedrine increased blood pressure due to the contractile properties of resistance vessels. Excessive contraction of the uterine arteries might cause fetal distress. This study was to determine the diameter of the uterine artery of female New Zealand rabbits after the administration of different doses of ephedrine using CT.Methods: Thirty-two rabbits were randomly divided into a control group (Group C), low dosage group (Group L), medium dosage group (Group M) and high dosage group (Group H). Normal saline and doses corresponding to the human dose of 7.5, 15 and 30 mg of ephedrine were injected respectively. The marginal ear and uterine artery diameters were measured 5, 10, 15, 30, and 45 min after injection using CT, and the hemodynamic changes were recorded.Results: The increase in mean arterial pressure in group M (p = 0.009), and H (p = 0.013) was higher than that in group C. Compared with group C, substantial contraction of the marginal ear artery was observed at the three doses of ephedrine. There were no differences in the uterine artery diameter among groups L, M and C, However, in Group H, a significant contraction of the uterine artery compared with the other groups (p < 0.001) was observed.Discussion: CT can be used to evaluate the effects of drugs on organs and blood vessels. Ephedrine can not only constrict the peripheral blood vessels but also do not affect the uterine artery at a dose of 15 mg or less. However, the dose should not exceed 30 mg, which may cause severe uterine artery depression.

Physiological asymmetry in uterine artery blood flow during the first trimester of pregnancy: New insights from a quantitative assessment using Pulsed-wave color Doppler and M-mode color power angio imaging

IntroductionThis study aimed to quantify uterine artery (UtA) blood flow and its hemodynamic components throughout the first trimester of pregnancy using Doppler ultrasound. MethodsCross-sectional cohort study involving women undergoing a routine ultrasound scan between 5 and 13 weeks' gestation. UtA blood flow was measured using Pulsed-wave Color Doppler to assess blood flow velocity across the cardiac cycle and M-mode Color Power Angio imaging to assess UtA diameter. A formula was applied to calculate systolic and diastolic blood flow volumes according to Poiseuille's equation. ResultsA total of 330 women with a single viable first-trimester pregnancy agreed to participate in this study. A stepwise increase in total UtA blood flow was observed during the first trimester, with significant increases at 7, 8, and 11 weeks. No significant differences in blood flow were observed between right and left UtAs. However, there was a statistically significant difference when comparing the UtA based on higher and lower blood flow, with a mean ± SD of 64.4% ± 10.5% through the former (p < 0.001). The increase in the UtA blood flow was secondary to an increase in the blood flow rate between 5 and 10 weeks. A significant increase in UtA diameter was only identified from 11 weeks onwards. DiscussionUtA blood flow in the first trimester is asymmetrical, at a constant ratio of ≈2:1. An interpretive model of the possible origin of this pattern during early pregnancy is proposed.

How hypoxia slows fetal growth: insights from high altitude.

A continuous oxygen supply is vital for fueling fetal growth, yet we know surprisingly little as to the precise mechanisms by which hypoxia reduces fetal growth. Animal models, while important, are limited by the enormous variability in mammalian physiologic responses to pregnancy. One of the earliest models for understanding hypoxia-induced reductions in fetal growth came from studies at high altitude that showed high altitude to have one of the strongest depressant effects on fetal growth. But all populations are not equally affected. Dolma et al., have added valuable information now showing that that Ladakhis, like Tibetans and Andeans, have a lower-than-expected frequency of small-for-gestational age (SGA) infants. Consistent with previous reports, these authors also found that uterine artery diameters at mid pregnancy (week 26–28) were larger in women giving birth to appropriate-for-gestational-age (AGA) than SGA infants at high but, interestingly, not at low altitude. Much remains to be learned about the physiologic pathways by which hypoxia impairs fetal growth. The variability among high-altitude populations and increasing sophistication of tools for investigating causal mechanisms have the potential to expand our presently limited means for identifying new treatments for hypoxia-related complications of pregnancy and fetal life.

Ultrasonographic findings of the corpus luteum and the gravid uterus during heat stress in dairy cattle.

The objectives of this study were to assess alterations in, echogenic appearance, size and blood flow in the corpus luteum, the placentomes and the blood flow in umbilical and uterine arteries that heat stress can cause in cooled pregnant dairy cows. Pregnant cows were allocated in two groups and the gravid uteri, along with the ipsilateral corpora lutea were examined during the winter (group W, n=9) or the summer (group S, n=10). The grey-scale ultrasound and colour flow imaging of the corpus luteum and placentome were performed. In addition, the umbilical and uterine artery diameters and haemodynamic parameters in the vessels were calculated. At the time of ultrasonographic examination, cortisol concentrations were higher, and progesterone levels tended to be lower in group S compared to group W. The grey-scale ultrasound evaluation of corpora lutea and placentomes was lower in group S compared to group W. The diameter of umbilical artery and the blood volume in the vessel were less in group S than in group W. We infer that heat stress affects foetal blood supply and possibly the structure of placentomes and corpora lutea, but it differently affects the blood flow characteristics in the umbilical and uterine arteries.

High-altitude population neonatal and maternal phenotypes associated with birthweight protection

BackgroundStates which reduce foetal oxygen delivery are associated with impaired intrauterine growth. Hypoxia results when barometric pressure falls with ascent to altitude, and with it the partial pressure of inspired oxygen (‘hypobaric hypoxia’). birthweight is reduced when native lowlanders gestate at such high altitude (HA)—an effect mitigated in native (millennia) HA populations. Studying HA populations offer a route to explore the mechanisms by which hypoxia impacts foetal growth.MethodsBetween February 2017 and January 2019, we prospectively studied 316 pregnant women, in Leh, Ladakh (altitude 3524 m, where oxygen partial pressure is reduced by 1/3) and 101 pregnant women living in Delhi (low altitude, 216 m above sea level).ResultsOf Ladakhi HA newborns, 14% were small for gestational age (<10th birthweight centile) vs 19% of newborn at low altitude. At HA, increased maternal body mass index, age, and uterine artery (UtA) diameter were positively associated with growth >10th weight centile.ConclusionsThis study showed that Ladakhi offspring birthweight is relatively spared from the expected adverse HA effects. Furthermore, maternal body composition and greater UtA size may be physiological HA adaptations and warrant further study, as they offer potential mechanisms to overcome hypoxia-related growth issues.ImpactReduced foetal oxygen delivery seen in native lowlanders who gestate at HA causes foetal growth restriction—an effect thought to be mitigated in native HA populations.We found that greater maternal body mass and UtA diameter were associated with increased offspring birthweight in a (Ladakh) HA population.This supports a role for them as physiological mediators of adaptation and provides insights into potential mechanisms that may treat hypoxia-related growth issues.

Evaluation of haemodynamic changes of uterine arteries using Doppler ultrasonography during different stages of pregnancy in Bos indicus cows

The objectives of the study were to evaluate haemodynamic changes and their relationships among ipsilateral (IPS) and contralateral (CONT) uterine arteries (UA) during different stages of pregnancy in Bos indicus cows. Multiparous pregnant cows (n=40) having a gestation length 30.47±0.54 (mean±SD) days were randomly enrolled and subjected to Doppler ultrasonography sequentially at 1st, 2nd, 4th, 6th and 8th months of gestation. Blood flow indices including diameter of UA (mm), blood flow volume (BFVo, ml/min), blood flow velocity (BFVe, cm/s), time-averaged maximum velocity (TAMV, cm/s), pulsatility index (PI) and resistance index (RI) were recorded. Data were analysed with mixed models using the PROC MIXED procedures, and Pearson correlation coefficients were calculated using the PROC CORR statement in SAS. The final statistical models included the fixed effects of side of UA, gestation month and the interaction between side of UA and gestation month. Results revealed that the mean diameter of the UA (12.13±0.22 vs. 10.09±0.22), BFVo (1236.33±0.55 vs. 770.41±0.55), BFVe (17.18±0.42 vs. 15.58±0.42) and TAMV (17.11±0.44 vs. 15.77±0.44) was higher (p<.05) in IPS as compared to CONT side of the UA in cows. However, PI and RI did not differ between IPS and CON arteries of uterus in cows. A very high and positive correlation (r=.89; p<.05) existed between the diameter of UA and BFVo starting from 1st to 8th months of gestation in IPS as well as CONT sides of UA. Moreover, TAMV was highly and positively correlated (r=.91; p<.05) with BFVe throughout the gestation. In conclusion, these haemodynamic changes in the UA could be used as a valuable validity tool to differentiate the compromised pregnancy in Bos indicus cows.

AMP-activated protein kinase activator AICAR attenuates hypoxia-induced murine fetal growth restriction in part by improving uterine artery blood flow.

Pregnancy at high altitude is associated with a greater incidence of fetal growth restriction due, in part, to lesser uterine artery blood flow. AMP-activated protein kinase (AMPK) activation vasodilates arteries and may increase uterine artery blood flow. In this study, pharmacological activation of AMPK by the drug AICAR improved fetal growth and elevated uterine artery blood flow. These results suggest that AMPK activation is a potential strategy for improving fetal growth and raising uterine artery blood flow in pregnancy, which may be important in pregnancy disorders characterized by uteroplacental ischaemia and/or fetal hypoxia. Uteroplacental hypoxia is associated with pregnancy disorders such as intrauterine growth restriction and preeclampsia, which are characterized by uteroplacental ischaemia and/or fetal hypoxia. Activation of AMP-activated protein kinase (AMPK) results in vasodilatation and is therefore a potential therapeutic strategy for restoring uteroplacental perfusion in pregnancy disorders. In this study, C57Bl/6 mice were treated with subcutaneous pellets containing vehicle, the AMPK activator AICAR (200 mg kg-1 day-1 ), or the AMPK inhibitor Compound C (20 mg kg-1 day-1 ) beginning on gestational day 13.5, and were exposed to hypoxia starting on gestational day 14.5 that induced intrauterine growth restriction. Pharmacological AMPK activation by AICAR partially prevented hypoxia-induced fetal growth restriction (P < 0.01), due in part to increased uterine artery blood flow (P < 0.0001). The proportion of total cardiac output flowing through the uterine artery was increased with AICAR in hypoxic mice (P < 0.001), suggesting that the vasodilator effect of AICAR was selective for the uterine circulation. Further, pharmacological inhibition of AMPK with Compound C reduced uterine artery diameter and increased uterine artery contractility in normoxic mice, providing evidence that physiological levels of AMPK activation are necessary for vasodilatation in healthy pregnancy. Two-way ANOVA analyses indicated that hypoxia reduced AMPK activation in the uterine artery and placenta, and AICAR increased AMPK activation in these tissues compared to vehicle. These findings provide support for further investigation into the utility of pharmacological AMPK activation for treatment of fetal growth restriction.

Uteroplacental Ischemia Is Associated with Increased PAPP-A2.

Residence at high altitude (> 2500m) has been associated with an increased frequency of preeclampsia. Pappalysin-2 (PAPP-A2) is an insulin-like growth factor binding protein-5 (IGFBP-5) protease that is elevated in preeclampsia, and up-regulated by hypoxia in placental explants. The relationships between PAPP-A2, altitude, and indices of uteroplacental ischemia are unknown. We aimed to evaluate the association of altitude, preeclampsia, and uterine artery flow or vascular resistance with PAPP-A2 levels. PAPP-A2, uterine artery diameter, volumetric blood flow, and pulsatility indices were measured longitudinally in normotensive Andean women residing at low or high altitudes in Bolivia and in a separate Andean high-altitude cohort with or without preeclampsia. PAPP-A2 levels increased with advancing gestation, with the rise tending to be greater at high compared to low altitude, and higher in early-onset preeclamptic compared to normotensive women at high altitude. Uterine artery blood flow was markedly lower and pulsatility index higher in early-onset preeclamptic normotensive women compared to normotensive women. PAPP-A2 was unrelated to uterine artery pulsatility index in normotensive women but positively correlated in the early-onset preeclampsia cases. We concluded that PAPP-A2 is elevated at high altitude and especially in cases of early-onset preeclampsia with Doppler indices of uteroplacental ischemia.

Clinical, Ultrasonographic, Bacteriological, Cytological and Histopathological Findings of Uterine Involution in Ewes with Uterine Infection.

The objectives of the study were (a) to study the characteristics of uterine involution in ewes that had developed subclinical uterine infection in the immediately post-partum period and (b) to evaluate effects of the infection in the subsequent reproductive performance of ewes. Uterine infection was induced in ewes (I, n = 10) by intrauterine inoculation of Escherichia coli; uninoculated controls were included (C, n = 12). Animals were examined at regular intervals before and post-inoculation. Clinical and ultrasonographic examinations were performed. Vaginal swab samples and biopsy uterine tissue samples were collected for bacteriological, cytological and histological examination. Finally, ewes were put to rams and reproductive performance was monitored. After challenge, it was ultrasonographically found that caruncular dimensions, myometrial thickness and diameter of uterine lumen were greater in I ewes. In these ewes, particular reduction of dimensions occurred during the second week post-partum, whilst in C ewes during the first week. The uterine artery diameter and the blood flow into the uterus were also greater in I than in C ewes. E. coli infection was more frequent and of longer duration in I than in C ewes: in 68.1% and 50.0% of ewes and 19.5 and 14 days, respectively. There was lower proportion of neutrophils and higher of lymphocytes in group I than in C. In inoculated ewes, there was histological evidence of uterine epithelial destruction, increased cellular infiltration, hyperaemia and extracasation, which persisted up to 42 days post-partum. During the subsequent reproductive season, all ewes in group I lambed normally and produced healthy and viable lambs. No significant difference in reproductive performance parameters were seen in I comparison to C ewes. It is concluded that the innate immunity of the uterus sufficed to counteract the bacterial infection, although the process of involution took longer than in healthy animals; moreover, the ultrasonographic examination is a useful means for assessment of the genital tract of ewes post-partum; finally, no adverse effects were noted in the subsequent reproductive performance of ewes.

EP19.02: Increased uterine artery diameter protects from altitude associated reduction in fetal growth

EP19.02: Increased uterine artery diameter protects from altitude associated reduction in fetal growth

Standartization of ultrasound examination of the pelvic organs in women

Introduction. In Russia, there has been no research comparing data obtained by ultrasound scanners of different firms, with a comprehensive assessment of pelvic organs in women.Purpose of the study. Compare the results of the study of the internal genitalia of healthy women, obtained on devices from Philips and GE Healthcare. Materials and methods. A comparison of the results of pelvic ultrasound examination in healthy patients of reproductive age (18–45 years), conducted on the expert level devices of GE Healthcare (Austria) and Philips (Netherlands) by the same doctor. Each group consisted of 30 people (15 women in the first and second phase of the cycle). Age did not have significant differences (p &gt; 0.05). Organometry (uterine volume, endometrial thickness, ovarian volume), dopplerometric parameters of blood flow in uterine arteries, such as maximum systolic and average blood flow rate (Vmax, Vmean), uterine artery diameter, arterial perfusion index (API) was calculated, vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) of the uterus and endometrium were obtained in 3D Doppler.Summary. When implementing new techniques should study the information about this method and rely on the regulatory parameters obtained on the devices of similar firms.

Hemodynamics of the uterine and umbilical arteries during the perinatal period in ewes

Examining feto-maternal blood flow is extremely important for accurate prenatal control and predicting adverse conditions during puerperium. We aimed to analyze blood flow of uterine artery (UA) and umbilical artery (UMA) from and subsequent to mid-gestation, lambing and postpartum of 15 ewes, subjected to lambing induction with aglepristone. Hemodynamic variables, diameter and blood flow of UA and UMA were determined by Doppler and B-mode ultrasonography at 60, 90 and 120 days of pregnancy, at 12 h before, 12 h after first aglepristone injection and 12 h after induction and days 1, 3, 5, 7, 15 and 30 after lambing. The UMA peak systolic:diastolic velocity (S/D), resistance index (RI) and pulsatility index (PI) decreased from mid-pregnancy until 120 d, whereas peak systolic velocity (PSV), end diastolic velocity (EDV) and time average maximum velocity (TAMAX) increased towards 120 d. The UMA RI additionally decreased at 12 h after lambing induction. The UMA diameter and volume increased from mid-gestation until 12 h before lambing induction. UA PSV and TAMAX increased from 60 until 90 days of pregnancy, while EDV, PSV and TAMAX decreased soon after parturition, with a further reduction at 7 days. The UA diameter and volume decreased during postpartum, stabilizing by 15 days after parturition. In conclusion, pregnancy is marked by progressive increase in uterine and umbilical blood flow, while lambing acutely diminishes umbilical vascular resistance, suggesting lack of progesterone influence on vasodilation. Conversely, puerperium is characterized by reduction in uterine blood supply mostly within the first 2 weeks of postpartum in sheep.

Activated NO pathway in uterine arteries during pregnancy in an IUGR rat model.

Insufficient development of the uteroplacental circulation may contribute to the development of intrauterine growth restriction (IUGR). We developed a rat model of IUGR by administering a low-Na+ diet. This diet reduces maternal blood volume expansion and uteroplacental perfusion. We hypothesized that an impaired endothelial function in radial arteries decreases vasorelaxation and lowers placental perfusion in this IUGR model. The objective was to assess radial uterine artery responses to vasoactive agents in the IUGR model versus controls. The vasoactive agents included phenylephrine and carbachol, use of a pressurized artery myograph, in the absence or presence of inhibitors of nitric oxide (NO) synthase [ N-nitro-l-arginine methyl ester (l-NAME)], cyclooxygenase (Ibuprofen), and endothelium-dependent hyperpolarization {apamin/1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole}, allowing better characterization of the mechanism implicated in endothelium-dependent relaxation. The results show that 1) the diameter of uterine radial arteries was significantly decreased in the IUGR group; 2) sensitivity to phenylephrine was reduced in IUGR arteries, which could be returned to control group values by inhibition of NO production; 3) the relaxation response to carbachol was increased in IUGR rats, principally mediated by endothelium-dependent hyperpolarization in both groups; 4) NO synthase inhibition by l-NAME decreased the maximum relaxation to carbachol only in the IUGR group; and 5) relaxation response to NO donors is increased in IUGR compared with control radial arteries. Contrary to the hypothesis, results in the IUGR model indicate that the NO pathway is activated in radial uterine arteries, most likely in compensation for the reduction in blood uteroplacental perfusion. NEW & NOTEWORTHY In contrast to genetic or surgical models of intrauterine growth restriction, the diet-induced model of reduced maternal volume expansion shows the nitric oxide pathway to be activated in the uterine artery, possibly from increased shear stress and/or placental factors.

Effect of exogenous estradiol Benzoate on uterine blood flow in postpartum dairy cows

The objective of this study was to assess the uterine blood flow following estradiol benzoate administration in Holstein-Friesian dairy cows by trans-rectal color Doppler ultrasonography. Six healthy lactating Holstein–Friesian cows were examined daily for 10 days starting at 4 weeks postpartum. All the cows, which were clinically healthy based on vaginal mucus scoring and endometrial cytology, were examined by trans-rectal Doppler ultrasonography to measure pulsatility index (PI), resistance index (RI), time average maximum velocity (TAMAX), blood flow volume (BFV) and diameter in the uterine arteries ipsilateral and contralateral to the previously pregnant uterine horn. On the third day of the experiment, the six cows were administered 10 mg intramuscular injection of estradiol-17β (E2).Blood samples were collected at the time of daily examination for the assessment ofE2concentrations.The PI and RI values decreased while TAMAX, BFV and diameter of uterine arteries increased in response toE2 administration (P < 0.05).There was a high correlation between both the ipsilateral and contralateral uterine arteries for all variables that were studied(r = 0.860, P < 0.0001, r = 0.922, P < 0.0001, r = 0.651, P < 0.0001, r = 0.879, P < 0.0001, r = 0.861, P < 0.0001 for the PI, RI, TAMAX, BFV and uterine arteries diameter, respectively).In conclusion, the greater blood concentrations ofE2may be responsible for the greater TAMAX, BFV, increased diameters and decreased PI and RI of the uterine arteries during the puerperium in dairy cows.

The large-conductance voltage- and Ca2+ -activated K+ channel and its γ1-subunit modulate mouse uterine artery function during pregnancy.

The uterine artery (UA) markedly vasodilates during pregnancy to direct blood flow to the developing fetus. Inadequate UA vasodilatation leads to intrauterine growth restriction and fetal death. The large-conductance voltage- and Ca2+ -activated K+ (BKCa ) channel promotes UA vasodilatation during pregnancy. We report that BKCa channel activation increases the UA diameter at late pregnancy stages in mice. Additionally, a BKCa channel auxiliary subunit, γ1, participates in this process by increasing channel activation and inducing UA vasodilatation at late pregnancy stages. Our results highlight the importance of the BKCa channel and its γ1-subunit for UA functional changes during pregnancy. Insufficient vasodilatation of the uterine artery (UA) during pregnancy leads to poor utero-placental perfusion, contributing to intrauterine growth restriction and fetal loss. Activity of the large-conductance Ca2+ -activated K+ (BKCa ) channel increases in the UA during pregnancy, and its inhibition reduces uterine blood flow, highlighting a role of this channel in UA adaptation to pregnancy. The auxiliary γ1-subunit increases BKCa activation in vascular smooth muscle, but its role in pregnancy-associated UA remodelling is unknown. We explored whether the BKCa and itsγ1-subunit contribute to UA remodelling during pregnancy. Doppler imaging revealed that, compared to UAs from wild-type (WT) mice, UAs from BKCa knockout (BKCa-/- ) mice had lower resistance at pregnancy day 14 (P14) but not at P18. Lumen diameters were twofold larger in pressurized UAs from P18 WT mice than in those from non-pregnant mice, but this difference was not seen in UAs from BKCa-/- mice. UAs from pregnant WT mice constricted 20-50% in response to the BKCa blocker iberiotoxin (IbTX), whereas UAs from non-pregnant WT mice only constricted 15%. Patch-clamp analysis of WT UA smooth muscle cells confirmed that BKCa activity increased over pregnancy, showing three distinct voltage sensitivities. The γ1-subunit transcript increased 7- to 10-fold during pregnancy. Furthermore, γ1-subunit knockdown reduced IbTX sensitivity in UAs from pregnant mice, whereas γ1-subunit overexpression increased IbTX sensitivity in UAs from non-pregnant mice. Finally, at P18, γ1-knockout (γ1-/- ) mice had smaller UA diameters than WT mice, and IbTX-mediated vasoconstriction was prevented in UAsfrom γ1-/- mice. Our results suggest that the γ1-subunit increases BKCa activation in UAs during pregnancy.

106: Novel MRI detection of impaired placental blood flow and fetal oxygen reserve in a non-human primate model of gestational protein restriction

We have recently developed novel placenta-specific MRI protocols to estimate placental oxygen reserve using blood oxygenation levels (T2* imaging). High oxyhemoglobin concentration has long T2* and correlates with areas of high perfusion as validated by dynamic contrast enhanced (DCE) MRI. Short T2* relates to areas of high deoxyhemoglobin concentration. Here our objective was to evaluate the adverse effects of maternal malnutrition on placental oxygen reserve and placental perfusion in vivo in a non-human primate model of gestational protein restriction (PR). Rhesus macaques were fed a control diet (CON, 26% protein, n=8) or switched to either a 33% PR (17% protein, n=8) or 50% PR (13% protein, n=8) diet before and during pregnancy. All underwent Doppler ultrasound (D-US) and fetal biometry measurements followed by MRI consisting of T2* and DCE measurements at gestational day 85 (G85) and G135 (term is G168). D-US was used to measure uterine artery (Uta) and umbilical vein velocimetry and diameter to calculate Uta volume blood flow (cQuta) and placental volume blood flow (cQuv). Pregnancy loss rates were 0/8 in controls, 1/8 in 33% PR, and 3/8 in 50% PR (1 prior to G135). Animals fed a 50%PR diet had significantly smaller fetal abdominal circumference (G135) and lower cQuta (G135) and cQuv (G85 and G135) versus CON (Fig 1). Additionally, by DCE-MRI, placental blood flow was significantly lower at G135 in animals fed a 50% PR diet (Fig 1). Distributions of T2* throughout the placenta (Fig 2) show significant global reductions in T2* (blood oxyhemoglobin) in animals fed a 50% PR diet vs. CON (G85 and G135). These data from a relevant translational model demonstrate that a 50% gestational PR diet reduces maternal placental perfusion, decreases fetal oxygen availability and increases fetal mortality. However, animals fed a 33% PR diet were similar to CON suggesting that placental reserve capacity is able to compensate for some PR, but not a 50% reduction. The perturbations observed with placental blood flow and fetal oxygen availability may explain the noted increased risk of human growth restriction and stillbirth with severe PR diets in the developing world. Our imaging abilities have allowed early identification of pregnancies affected by placental dysfunction and is a first step in improving outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)