Uterine Artery Blood Flow Research Articles

Rad-mediated inhibition of CaV1.2 channel activity contributes to uterine artery haemodynamic adaptation to pregnancy.

The striking increase of uterine blood flow during pregnancy is essential for normal fetal development as well as for cardiovascular well-being of the mother. Yet, the underlying mechanisms of pregnancy-mediated vasodilatation of the uterine artery are not fully understood. In this study, we test the hypothesis that Rad, a monomeric G protein, is a novel regulatory mechanism in inhibiting CaV1.2 channel currents in uterine artery haemodynamic adaptation to pregnancy in a sheep model. We found that pregnancy significantly upregulates Rad expression and decreases CaV1.2 channel currents in uterine arterial smooth muscle cells. Rad knockdown ex vivo and in vivo increases CaV1.2 activity and channel window currents by reducing steady-state inactivation in uterine arteries of pregnant sheep, recapitulating the phenotype of uterine arteries in non-pregnant animals. Moreover, Rad knockdown in vivo in pregnant sheep enhances myogenic tone and phenylephrine-induced vasoconstriction of uterine arteries. Whereas knockdown of Rad has no effect on mesenteric arterial CaV1.2 channel activity and mean arterial blood pressure, it significantly increases uterine vascular resistance and decreases uterine artery blood flow. Our study reveals a novel cause-and-effect mechanism of Rad in pregnancy-induced suppression of CaV1.2 channel activity in uterine arteries to facilitate increased uterine blood flow, providing new insights into fundamental mechanisms of uterine haemodynamic adaptation to pregnancy. KEY POINTS: Pregnancy suppresses CaV1.2 channel currents in uterine arterial smooth muscle cells. Rad, a monomeric G protein, is upregulated in uterine arteries of pregnant sheep. Rad knockdown ex vivo or in vivo increases CaV1.2 channel currents in uterine arteries from pregnant ewes. In vivo knockdown of Rad elevates uterine vascular resistance and decreases uterine blood flow in pregnant sheep. The study reveals a novel mechanism of Rad in pregnancy-induced suppression of CaV1.2 channel activity in uterine arterial haemodynamic adaptation to pregnancy.

Effects of miR-214-5p and miR-21-5p in hypoxic endometrial epithelial-cell-derived exosomes on human umbilical cord mesenchymal stem cells

BACKGROUND Thin endometrium seriously affects endometrial receptivity, resulting in a significant reduction in embryo implantation, and clinical pregnancy and live birth rates, and there is no gold standard for treatment. The main pathophysiological characteristics of thin endometrium are increased uterine arterial blood flow resistance, angiodysplasia, slow growth of the glandular epithelium, and low expression of vascular endothelial growth factor, resulting in endometrial epithelial cell (EEC) hypoxia and endometrial tissue aplasia. Human umbilical cord mesenchymal stem cells (HucMSCs) promote repair and regeneration of damaged endometrium by secreting microRNA (miRNA)-carrying exosomes. However, the initiation mechanism of HucMSCs to repair thin endometrium has not yet been clarified. AIM To determine the role of hypoxic-EEC-derived exosomes in function of HucMSCs and explore the potential mechanism. METHODS Exosomes were isolated from normal EECs (EEC-exs) and hypoxia-damaged EECs (EECD-exs), before characterization using Western blotting, nanoparticle-tracking analysis, and transmission electron microscopy. HucMSCs were cocultured with EEC-exs or EECD-exs and differentially expressed miRNAs were determined using sequencing. MiR-21-5p or miR-214-5p inhibitors or miR-21-3p or miR-214-5p mimics were transfected into HucMSCs and treated with a signal transducer and activator of transcription 3 (STAT3) activator or STAT3 inhibitor. HucMSC migration was assessed by Transwell and wound healing assays. Differentiation of HucMSCs into EECs was assessed by detecting markers of stromal lineage (Vimentin and CD13) and epithelial cell lineage (CK19 and CD9) using Western blotting and immunofluorescence. The binding of the miRNAs to potential targets was validated by dual-luciferase reporter assay. RESULTS MiR-21-5p and miR-214-5p were lowly expressed in EECD-ex-pretreated HucMSCs. MiR-214-5p and miR-21-5p inhibitors facilitated the migratory and differentiative potentials of HucMSCs. MiR-21-5p and miR-214-5p targeted STAT3 and protein inhibitor of activated STAT3, respectively, and negatively regulated phospho-STAT3. MiR-21-5p- and miR-214-5p-inhibitor-induced promotive effects on HucMSC function were reversed by STAT3 inhibition. MiR-21-5p and miR-214-5p overexpression repressed HucMSC migration and differentiation, while STAT3 activation reversed these effects. CONCLUSION Low expression of miR-21-5p/miR-214-5p in hypoxic-EEC-derived exosomes promotes migration and differentiation of HucMSCs into EECs via STAT3 signaling. Exosomal miR-214-5p/miR-21-5p may function as valuable targets for thin endometrium.

Late-gestation maternal undernutrition induces circulatory redistribution while preserving uteroplacental function independent of fetal glycaemic state.

Programming effects of maternal undernutrition on fetal metabolic and cardiovascular systems are well elucidated, yet a detailed characterization of maternal haemodynamics is not available. This study used comprehensive cardiovascular magnetic resonance (CMR) imaging to quantify maternal haemodynamics after 29days (111-140 days) of late-gestation undernutrition (LGUN) in pregnant sheep. Control ewes received 100% of metabolizable energy requirements (MERs, n=15), whereas LGUN ewes were globally nutrient restricted to 50% MER (n=18), with a subset of fetuses undergoing continuous glucose infusion (LGUN+G, n=6/18). Ewes underwent CMR (138-140 days' gestation), and placental tissue was collected the next day. Ewes in both LGUN groups had reduced body weight and mean blood glucose concentration across gestation. Ventricular dimensions were lower in both LGUN groups. Uterine artery blood flow (QUtA) was elevated in the LGUN group compared with controls, whereas peripheral blood flow was reduced and further diminished in LGUN+G. Maternal weight change correlated with all haemodynamic parameters across all groups. Uteroplacental oxygen and glucose delivery were increased in LGUN compared to control ewes, whereas uteroplacental oxygen consumption was preserved. LGUN did not impact placental or fetal weight, and markers of brain-sparing physiology were absent. Placental expression of insulin-like growth factors (IGF-1 and IGF-2) and their receptors, glucose, fatty acid (FA) or amino acid transporters and markers of angiogenesis was not impacted. FA transporter expression was positively correlated with QUtA, and FA binding protein correlated negatively with maternal weight change. Maternal cardiovascular adaptations in response to LGUN manifest as preservation of placental growth and function, thereby preserving fetal growth. KEY POINTS: Maternal undernutrition during pregnancy alters fetal metabolic and cardiovascular physiology, but little is known about alterations in maternal haemodynamics. Late-gestation undernutrition (LGUN) and LGUN+G redirected maternal blood flow from the periphery to the uteroplacental unit, concomitantly increasing the delivery of glucose and oxygen to the uteroplacental unit. Substrate transporter expression and uteroplacental oxygen consumption were preserved in LGUN and LGUN+G, suggesting prioritization of the placenta. This study is the first to report detailed maternal haemodynamics in the setting of maternal undernutrition, where placental growth and function were maintained, ultimately preserving fetal oxygen metabolism and growth.

Maternal-Fetal Blood Flow and Progesterone Concentration in Ewes Sheared at Mid or Late-Pregnancy.

These studies aimed to determine if shearing ewes at the second or last third of gestation modify the uterine and placentome blood flow, placentome size, and maternal progesterone concentration. Pregnant ewes were assigned to four groups of 12 ewes each according to the gestation period: mid-pregnancy sheared (on day 90 of pregnancy) or unshorn group; and late-pregnancy sheared group (on day 121 of pregnancy) or unshorn group. In both experimental periods, using spectral Doppler ultrasonography, placentomes and uterine artery blood flow and placentome size were evaluated 14 days before and 6 days after shearing. An additional measurement was performed 26 days after shearing in mid-pregnant ewes. Serum progesterone concentration was measured before shearing 4, 24, 72 h, and 22 days after shearing. The uterine artery's end-diastolic velocity (EDV) tended to be greater in the sheared than in the non-sheared ewes (p = 0.1). Peak systolic velocity (PSV) and EDV of placentome increased (p = 0.05 and p = 0.008, respectively) on day 26, accompanied by an increase in placentome area (p = 0.035) in mid-pregnant ewes. In late-pregnant ewes, uterine artery and placentome blood flow and size did not vary. Progesterone concentration varied with time but was not affected by shearing. In conclusion, shearing triggered an increase in placentome size and some changes in blood flow only when ewes were sheared during the second third of their pregnancy. Shearing ewes either the second or last third of gestation did not affect uterine artery blood flow and progesterone secretion.

Effect of low-dose aspirin on mid-luteal phase uterine Artery blood flow in women with unexplained recurrent pregnancy loss

Objectives: As a possible therapy for recurrent pregnancy loss, this study sought to ascertain if low-dose aspirin was effective in increasing uterine artery blood flow. Study Design: This investigation was structured as a single-arm clinical trial Patients and Methods: All participants were aged 39 years or younger and had no prior or current indications of abnormal glucose tolerance, thyroid dysfunction, hyperprolactinemia, or Antiphospholipid antibody syndrome. Bilateral assessments of the Systolic/Diastolic (S/D) ratio, Resistive Index (RI), and Pulsatility Index (PI) were conducted in the chosen patients in the mid-luteal phase, before to and following a minimum of two weeks of low-dose aspirin administration. Results: The results of this investigation showed significant variation in the S/D and PI prior to and following aspirin administration. There was no discernible shift in RI. The analysis revealed a statistically significant reduction in uterine artery PI after aspirin administration (1.92±0.29) compared to the pre-treatment value (2.22±0.27), with a p-value of 0.0001. Remarkably, the pulsatility indices of the left and right uterine arteries did not significantly differ from one another. Conclusion: For women who have a history of miscarriages, low-dose aspirin can be recommended as an adjuvant therapy as it effectively improves uterine artery blood flow in these patients. However, more well-designed research is required to ascertain whether improved pregnancy outcomes are correlated with improved uterine perfusion. The current study supported the aspirin guideline for women with a history of recurrent miscarriages by showing that aspirin treatment resulted in a reduction in uterine artery PI.

Low-dose aspirin improves blood perfusion of obstetric anticardiolipin syndrome in China.

This study evaluates the endometrial receptivity of obstetric anticardiolipin syndrome (OAPS) patients using various ultrasound indicators and the efficacy of low-dose aspirin (LDA) treatment. This retrospective study recruited patients from Shanghai Ren Ji Hospital, China from January 2022 to December 2023. Doppler parameters of the endometrium and uterine artery blood flow were recorded to assess the endometrial receptivity of OAPS patients compared with normal pregnant women and an other immune diseases group. The receiver operating characteristic curve was used to predict the risk of OAPS patients. Doppler parameters of OAPS patients were conducted repeatedly after a 2-month period of treatment with LDA. Compared with normal pregnant women, the OAPS group showed remarkably increased endometrial perfusion resistance (PI, RI, S/D) and uterine artery perfusion resistance (RI and S/D) (P < 0.001) and had good predictive values (area under the curve = 0.806, 0.976, 0.942, 0.902, and 0.901, respectively). The endometrial thickness of the OAPS group was much thinner than that of the normal group (P < 0.001). Uterine blood flow impedance PI showed no difference in both groups (P = 0.68). In comparison to other autoimmune diseases, the OAPS group also showed an increasing trend in the resistance of endometrium and uterine artery blood flow. After LDA treatment, there was an obvious improvement in the endometrial blood flow perfusion in the OAPS group (P < 0.01). Compared with the normal group and other autoimmune diseases, the resistance of endometrial and uterine artery blood flow in the OAPS group was increased significantly. The Doppler index showed the predictive value of OAPS, and it was confirmed that LDA could enhance blood perfusion among OAPS women.

Combination therapy of Sanjie Zhentong capsules for endometriosis: Impact on hormone regulation and serum expression of FOLR1 and MSLN.

Examining the impact of Sanjie Zhentong capsules on hormone levels and serum expression of folate receptor 1 (FOLR1) and Mesothelin (MSLN) in endometriosis patients. A cohort of 150 endometriosis patients admitted between June 2019 and June 2023 was divided into 2 groups based on Sanjie Zhentong intake, comprising 75 cases each. Comparative analyses encompassed uterine artery hemodynamic parameters, ultrasound (B-mode) findings, Visual Analog Scale scores, traditional Chinese medicine symptom scores, Endometriosis Health Profile-30 scores, and serum levels of FOLR1, MSLN, and sex hormones before and after treatment. Post-treatment, both groups exhibited increased peak systolic velocity compared to pretreatment, with the Sanjie Zhentong group showing a significantly higher increase (P < .05). Moreover, resistance index decreased in both groups post-treatment, with the Sanjie Zhentong group displaying a greater reduction (P < .05). Adnexal mass diameters, endometrial thickness, and uterine volume decreased post-treatment in both groups, with the Sanjie Zhentong group experiencing a more pronounced decrease (P < .05). Serum FOLR1, MSLN, and sex hormone levels also decreased post-treatment in both groups, with the Sanjie Zhentong group exhibiting a more significant decrease (P < .05). Additionally, pain scores, traditional Chinese medicine symptoms, and Endometriosis Health Profile-30 scores decreased post-treatment in both groups, with the Sanjie Zhentong group demonstrating a greater reduction (P < .05). Sanjie Zhentong capsules demonstrate efficacy in regulating sex hormones, reducing serum FOLR1 and MSLN expression, alleviating pain, shrinking adnexal masses, decreasing uterine size, and improving uterine artery blood flow in endometriosis patients.

Vascular Alterations in Uterine and Ovarian Hemodynamics and Hormonal Analysis throughout Pregnancy Loss in Cows under Heat Stress.

This current study examined the ovarian (OA) and middle uterine arteries (MUA) blood flow under heat stress conditions regarding hormonal status (progesterone (P4), estradiol (E2), and nitric oxide metabolites (NOMs) assays). Eighteen pluriparous cows were examined, with twelve only being subjected to the natural mating as the other six animals were not bred. Pregnancy diagnosis was confirmed at day 30 by embryonic heartbeat and CL graviditatis (n = 6; pregnant), but some animals (n = 6) showed early embryonic death (EED), with the presence of control cows (n = 6). In the pregnant group, luteal diameter (cm) increased after mating, while in the pregnancy loss group it increased (p < 0.05) until reaching day 38 (1.41 ± 0.03), then decreased again. Luteal vascularity was declined in cows with EED after day 36 (p < 0.05) and reached its lowest level at day 50. P4 levels elevated in cows with EED until day 36 (13.64 ± 0.11) then declined. Both ipsilateral OA and MUA Doppler indices were declined in both groups except in cows who suffered from EED; both were elevated from day 38 until day 50 after mating. Ipsilateral peak systolic point (PSV cm/sec) of OA and MUA was elevated in both groups (p < 0.05), but in cows with EED this parameter was declined. E2 and NOMs levels were declined in cows with EED from day 40 and day 38 after mating (p < 0.05), respectively. This study provided novel data on the relations among the luteal diameter, E2, P4, and NOM levels, and luteal hemodynamics that predicts the amount of blood supply, which acts as a sensitive parameter to detect the alterations in luteal function during the first 50 days after mating.

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.

Correlation Between Serum Markers and Midluteal Phase Doppler Assessment of Uterine Arterial Blood Flow in Unexplained Recurrent Pregnancy Loss.

This study aimed to determine changes in uterine artery Doppler parameters in unexplained recurrent pregnancy loss (URPL) and to explore serum markers possibly associated with them. This retrospective case-control study included 107 URPL women and 107 control women. The mean pulsatility index (PI), resistive index (RI), and systolic-to-diastolic values for uterine arteries in URPL women were significantly higher than those in the controls (P < 0.05). The cutoff values of PI and RI differentiating the women with URPL from the controls were confirmed by ROC and Youden's index. Given a PI cutoff value of 2.6, the prevalence of URPL was significantly elevated in the high-PI group (74.58%) compared with that in the low-PI group (40.65%, P < 0.0001), with sensitivity and specificity of 63% and 69%, respectively. With an RI cutoff value of 0.86, the prevalence of URPL in the high-RI group (65.28%) was significantly elevated compared with that in the low-RI group (42.25%, P = 0.001), with sensitivity and specificity of 66% and 75%, respectively. The levels of serum D-dimers and anticardiolipin antibody (ACA)-IgM in URPL women were significantly higher than those in the controls. A positive correlation existed between the levels of ACA-IgM and uterine artery RI in URPL women (r = 0.43, P < 0.01). These results indicated that URPL women may be at a relatively high risk of a prothrombotic state, and the increased ACA-IgM deserves attention for its role in the elevated uterine artery Doppler parameters in URPL women.

Discussion on the evaluation of the therapeutic efficacy of uterine artery blood flow parameters and serum PLGF and sFlt-1 in patients with recurrent spontaneous abortion

ObjectiveTo investigate the effects of different drug treatments on uterine artery blood flow parameters, serum placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and sFlt-1/PLGF in patients with recurrent spontaneous abortion and to explore the predictive value of uterine artery blood flow parameters, serum PLGF, sFlt-1, and sFlt-1/PLGF for pregnancy outcomes.MethodsThis retrospective cohort study included 173 patients who experienced recurrent spontaneous abortion and 100 control patients. Patients with recurrent spontaneous abortion were divided into an aspirin group (75 patients), aspirin combined with low molecular weight heparin (LMWH) group (68 patients), and non-drug group (30 patients) based on different drug treatments. Uterine artery blood flow parameters at gestational weeks 30-31+6 were monitored for the four groups, and serum samples were collected at gestational weeks 30-31+6 to measure the levels of serum PLGF and sFlt-1 and calculate the sFlt-1/PLGF ratio.Results1. Uterine artery blood flow parameters at gestational weeks 30-31+6 were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p<0.05). 2. Serum PLGF levels and the sFlt-1/PLGF ratio at gestational weeks 30-31+6 were significantly lower in the non-drug group than in the aspirin group, combined drug group, and control group, while serum sFlt-1 levels were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p<0.05). 3. Serum PLGF, sFlt-1, and sFlt-1/PLGF had lower diagnostic efficiency for predicting hypertensive disorders during pregnancy than the combined diagnostic efficiency of serum PLGF, sFlt-1, and sFlt-1/PLGF with uterine artery blood flow parameters at gestational weeks 30-31+6.ConclusionAspirin and aspirin combined with LMWH can upregulate serum PLGF and decrease serum sFlt-1 levels in patients with recurrent spontaneous abortion, reduce the miscarriage rate, and significantly improve pregnancy outcomes. The combination of serum PLGF, sFlt-1, sFlt-1/PLGF, and uterine artery blood flow parameters can effectively predict hypertensive disorders during pregnancy.

The Effect of the Levonorgestrel-Releasing Intrauterine System on Myometrial Blood Flow in Patients With Heavy Menstrual Bleeding.

Background Abnormal uterine bleeding constitutes a vexing issue among female patients, substantially impacting their quality of life. Surgical interventions, particularly hysterectomy, contribute to the psychological, physical, and financial burden on families and, by extension, the healthcare system. Levonorgestrel-releasing intrauterine system (LNG-IUS) represents a conservative management approach and emerges as a beneficial option for affected patients. The present study aims to elucidate color Doppler changes in the uterine artery pre- and post-LNG-IUS insertion. Objective The primary objectives encompass an investigation into the variations in Doppler indices (resistance index (RI) and pulsatility index (PI)) within the arcuate and radial branches of the uterine artery, as well as the assessment of endometrial thickness before LNG-IUD insertion, at three months, and six months post-insertion. Secondary outcomes include evaluating changes in pictorial blood assessment chart (PBAC) scores before insertion, at three months, and at six months after LNG-IUS insertion. Methods A cross-sectional study was conducted at the Department of Obstetrics and Gynecology at All India Institute Of Medical Sciences (AIIMS), Nagpur. A cohort of 25 women underwent LNG-IUS insertion. The endometrial cavity, RI, and PI of both arcuate and radial arteries were assessed before LNG-IUS insertion and at three and six months after insertion. Results The PI of the arcuate artery exhibited minimal alteration over the six-month duration, with a p-value of 0.43. Conversely, the RI demonstrated a statistically significant increase over the same period (p = 0.03). Conversely, the radial artery exhibited no statistically significant changes in either PI or RI (p = 0.39 or 0.13, respectively). Conclusion Following six months of LNG-IUS utilization, a substantial reduction in endometrial thickness and menstrual flow was observed, concomitant with an improvement in hemoglobin levels. Notably, the PI of both the arcuate and radial arteries demonstrated no significant change. Although the RI of the arcuate artery increased, its clinical relevance may be limited. Consequently, the observed reduction in menstrual bleeding cannot conclusively be ascribed to diminished blood flow in uterine arteries.

Comparative study of different dosages of grain-sized moxibustion on uterine artery blood flow in patients with cold and dampness primary dysmenorrhea.

To observe the differences in the effects of different dosages of grain-sized moxibustion on uterine artery blood flow in patients with cold and dampness primary dysmenorrhea (PD). A total of 60 patients with PD were randomly divided into 3 groups with 20 cases in each group. Acupoints Sanyinjiao (SP6), Diji (SP8) and Xuehai (SP10) were selected in all the 3 groups, and different dosages of grain-sized moxibustion were used (3 moxa cones, 6 moxa cones, 9 moxa cones) respectively. Treatment started 7 days before menstruation for 3 times, lasting for a total of 3 menstrual cycles. The values of uterine artery blood flow parameters including pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio (S/D) were recorded before and after treatment. The visual analog scale (VAS) score and cox menstrual symptom scale (CMSS) score (including severity ［CMSS-S］ and time of duration ［CMSS-T］) were evaluated before treatment, at the end of each menstrual cycle, and one menstrual cycle after treatment. The values of uterine artery blood flow parameters (PI, RI, S/D) after treatment in the 9 moxa cones group were lower than those before treatment, as well as lower than those in the 3 and 6 moxa cones groups after treatment (P<0.05). The VAS scores of the 3 moxa cones group were lower than those before treatment in the first and second cycle (P<0.05). The VAS scores of the 6 and 9 moxa cones groups were lower than those before treatment at each observation point (P<0.05), and were lower than those of the 3 moxa cones group in the third cycle of treatment and follow-up period (P<0.05). And the VAS score of the 9 moxa cones group was lower than that of the 6 moxa cones group during the follow-up period (P<0.05). Compared with the scores before treatment, the CMSS-T scores at each observation point after treatment were lower in the 9 moxa cones group (P<0.05)；the CMSS-T scores in the second and third cycle after treatment, and follow-up period were lower in the 6 moxa cones group (P<0.05), with the CMSS-S scores in the second and third cycle after treatment, and follow-up period lower in the 6 and 9 moxa cones groups (P<0.05). The CMSS-T and CMSS-S scores of the 6 and 9 moxa cones groups were lower than those of the 3 moxa cones group in the third cycle and follow-up period (P<0.05). The CMSS-T and CMSS-S scores of the 9 moxa cones group were lower than those of the 6 moxa cones group during the follow-up period (P<0.05). Grain-Sized moxibustion has dose-effect relationship in the treatment of PD. Compared with 3 and 6 moxa cones groups, 9 moxa cones group has advantages in improving uterine artery blood flow parameters and alleviating dysmenorrhea symptoms in PD patients.

Placental biophysical model for prediction of early onset fetal growth restriction in first and second trimester of pregnancy: A prospective cohort study

IntroductionTo assess the placental biometry, placental biomarkers and uterine artery Doppler in each trimester of pregnancy for prediction of early-onset fetal growth restriction (EO FGR). MethodsIn this prospective cohort study placental biometry; biomarkers PAPP-A, sFLT-1, and PlGF along with the uterine artery blood flow evaluation was done serially at 11–14, 20–24 and 28–32 weeks of gestation. The above parameters were compared between women with early onset FGR and controls. ResultsOut of 1008 fully followed cases, the small for gestational age fetuses were 227/1008 (22.5 %), and EO FGR were 84/1008(8.3 %).The placental length, volume, and PlGF levels were significantly lower, whereas the uterine artery PI(Ut PI) was significantly higher at all time points among cases. The sFLT-1 level showed a significant increase among cases, whereas it decreased among controls from the first to the second trimester. The detection rate using PV/UtA PI was 60 % in the first trimester and 66.7 % in the second trimester at 30 % FPR. ConclusionThe PV/Ut PI in first and the second trimester was a good marker for the prediction of pregnancies at increased risk of developing EO FGR.

H2S donor GYY4137 mitigates sFlt-1-induced hypertension and vascular dysfunction in pregnant rats†.

Gestational hypertension, often associated with elevated soluble Fms-related receptor tyrosine kinase 1 (sFlt-1), poses significant risks to both maternal and fetal health. Hydrogen sulfide (H2S), a gasotransmitter, has demonstrated blood pressure-lowering effects in hypertensive animals and humans. However, its role in pregnancy-induced hypertension remains unclear. This study investigated the impact of GYY4137, a slow-release H2S donor, on sFlt-1-induced hypertension in pregnant rats . Pregnant rats were administered sFlt-1 (6μg/kg/day, intravenously) or vehicle from gestation day (GD) 12-20. A subset of these groups received GYY4137 ( 50mg/kg/day, intraperitoneal) from GD 16-20. Serum H2S levels, mean arterial blood pressure, uterine artery blood flow, and vascular reactivity were assessed. Elevated sFlt-1 reduced both maternal weight gain and serum H2S levels. GYY4137 treatment restored both weight gain and H2S levels in sFlt-1 dams. sFlt-1 increased mean arterial pressure and decreased uterine artery blood flow in pregnant rats. However, treatment with GYY4137 normalized blood pressure and restored uterine blood flow in sFlt-1 dams. sFlt-1 dams exhibited heightened vasoconstriction to phenylephrine and GYY4137 significantly mitigated the exaggerated vascular contraction. Notably, sFlt-1 impaired endothelium-dependent relaxation, while GYY4137 attenuated this impairment by upregulating eNOS protein levels and enhancing vasorelaxation in uterine arteries. GYY4137 mitigated sFlt-1-induced fetal growth restriction. In conclusion, sFlt-1 mediated hypertension is associated with decreased H2S levels. Replenishing H2S with the donor GYY4137 mitigates hypertension and improves vascular function and fetal growth outcomes. This suggests modulation of H2S could offer a novel therapeutic strategy for managing gestational hypertension and adverse fetal effects.

Коагуляційні характеристики пуповинної крові при затримці росту плода

Fetal growth restriction (FGR) is a common complication of pregnancy associated with severe perinatal consequences, a significant part of which is hemorrhagic and thrombotic disorders. Fetuses with FGR have thrombocytopenia, platelet dysfunction, and distortion of standard coagulation tests. There are few studies of the coagulation system in such newborns in vivo in the literature. Аim - to assess the relationship between the Doppler criteria of FGR and the kinetic manifestations of umbilical artery blood coagulation and fibrinolysis according to rotational thromboelastometry. Materials and methods. Prenatal Doppler parameters and postpartum kinetic parameters of blood coagulation and fibrinolysis in 118 newborns from singleton births were analyzed: the Group I - 67 newborns with FGR; the Group II - 51 full-term newborns from healthy mothers. Results. A significant decrease in the uterine and umbilical arteries resistance and blood flow velocity in FGR cases has been established. Thromboelastometric tests in the umbilical cord blood of the Group I newborns showed faster than in the Group II the blood clot formation, its greater firmness and delayed fibrinolysis. Comparison using rank correlation showed a relationship of average strength between the velocity of blood flow in the umbilical cord arteries and the blood clot firmness. Correlation between blood flow velocity in the midbrain and uterine arteries and coagulation indicators are weak. Conclusions. Reduced resistance index in the middle cerebral artery of fetuses with FGR indicates reduced resistance in these vessels, which should be regarded as signs of decentralization of fetal circulation. The blood of newborns with FGR is dominated by the processes of increased coagulation and slowing down of fibrinolysis, regardless of the date of birth. An increase in the pulsation index in the umbilical cord arteries during pregnancy can be considered a prognostically favorable hemodynamic characteristic in FGR. The study was carried out in accordance with the principles of the Helsinki Declaration. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. The authors declare that there is no conflict of interest.

Perivascular Adipose Tissue and Uterine Artery Adaptations to Pregnancy.

Pregnancy is characterized by longitudinal maternal, physiological adaptations to support the development of a fetus. One of the cardinal maternal adaptations during a healthy pregnancy is a progressive increase in uterine artery blood flow. This facilitates sufficient blood supply for the development of the placenta and the growing fetus. Regional hemodynamic changes in the uterine circulation, such as a vast reduction in uterine artery resistance, are mainly facilitated by changes in uterine artery reactivity and myogenic tone along with remodeling of the uterine arteries. These regional changes in vascular reactivity have been attributed to pregnancy-induced adaptations of cell-to-cell communication mechanisms, with an emphasis on the interaction between endothelial and vascular smooth muscle cells. Perivascular adipose tissue (PVAT) is considered the fourth layer of the vascular wall and contributes to the regulation of vascular reactivity in most vascular beds and most species. This review focuses on mechanisms of uterine artery reactivity and the role of PVAT in pregnancy-induced maternal vascular adaptations, with an emphasis on the uterine circulation.

Gestational Long Term High-Altitude Hypoxia and Metabolomic Reprogramming in Uterine Arteries of Adult Sheep

Long term hypoxic stress during pregnancy causes a reduction in uterine blood flow, compromising oxygen and nutrient delivery to the fetus. There are multiple epigenetic factors involved in the structural and functional impairments that underlie the impairments in uterine arterial function. Evidence indicates that oxidative stress plays an important role to the decrements in blood flow following high altitude pregnancy. The purpose of the current study was to test the hypothesis that changes in oxylipin and endocannabinoid signaling are important to the increases in oxidative stress along with changes in glucose and fat metabolism. To further understand the mechanisms associated with disruption of uterine artery blood flow due to high altitude pregnancy, we examined a high altitude pregnant sheep model. Pregnant and non-pregnant sheep were housed either at low (700m) or high altitude (3801 meters) for 110+ days of pregnancy. Uterine arteries were excised from pregnant and non-pregnant sheep and targeted as well as untargeted metabolomic analyses were performed to test the hypothesis that hypoxia increases oxidative stress and reduces oxidative metabolism. Enrichment analysis of the metabolites show that hypoxia impacted several key biochemical pathways. At high altitude there were decreases in Alpha Linolenic Acid and Linoleic Acid Metabolism along with reductions in Pyruvate Metabolism and antioxidants. Further to this, there was an increase in the metabolism of Arachidonic Acid, Glycerolipids, and Methionine, which are linked to inflammation, cell signaling, and cell growth. Fully understanding how increased oxidative stress and inflammatory pathways along with decreased antioxidant capacity and changes in cellular metabolism is tied to malformations in uterine arterial structure and function following high altitude gestation is an active area of investigation. This work was supported by the National Institutes of Health Grants NIH R01HL155295, R01HL149608, R03HD098477, P01HD083132, and U24DK097154. Additional support was provided by the Loma Linda University School of Medicine and West Coast Metabolomics Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Curative effect of motherwort combined with ethinylestradiol-cyproterone acetate on dysfunctional uterine bleeding

ABSTRACT Objective This study aimed to investigate the curative effect of motherwort combined with ethinylestradiol-cyproterone acetate (EE/CPA) on dysfunctional uterine bleeding (DUB). Methods Atotal of 68 patients with DUB were divided into a single medication group (treated with EE/CPA) and a combination medication group(treated with motherwort and EE/CPA). The clinical efficacy, uterine hemodynamic parameters, sex hormone levels, coagulation index levels, blood routine test levels, and adverse reactions of patients were evaluated. Results After three months of treatment, total treatment response rate of the combination medication group was significantly higher than that of the single medication group. Decreased uterine volume, endometrial thickness and resistance index (RI), increased pulsatility index(PI), average flow rate, and uterine artery blood flow, as well asreduced follicle-stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2), progesterone (P), activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen (FIB), thrombin time(TT), platelet count (PLT), red blood cell (RBC), and hemoglobin (Hb)levels were witnessed in patients of the two groups. In thecombination medication group, there exhibited reduced uterine volume, endometrial thickness and RI, elevated PI, average flow rate, and uterine artery blood flow, reduced P, E2, FSH, LH, aPTT, PT, FIB, TT,PLT, RBC, and Hb levels in comparison to the single medication group. Conclusion The combination of motherwort and EE/CPA is clinically effective in the treatment of DUB.

Analysis of the uterine artery pulsatility index on the day of endometrial transformation and pregnancy outcomes of patients undergoing frozen-thawed embryo transfer.

The objective was to analyze the impact of the uterine artery pulsatility index (PI) on pregnancy outcomes by measuring uterine artery blood flow on the day of endometrial transformation in patients undergoing frozen-thawed embryo transfer (FET). This was a case-control study. In total, 2,036 patients who underwent FET at the Third Affiliated Hospital of Zhengzhou University from October 2019 to September 2020 were included. The patients were divided into a clinical pregnancy group and a nonclinical pregnancy group according to pregnancy outcome. A multivariate logistic regression model was used to analyze the factors affecting the clinical pregnancy rate. The receiver operating characteristic (ROC) curve was used to determine the optimal mean PI cutoff value of 1.75. After 1:1 propensity score matching (PSM), 562 patients were included. For statistical description and analysis, the patients were divided into two groups: a group with a mean PI > 1.75 and a group with a mean PI ≤ 1.75. The clinical pregnancy group included 1,218 cycles, and the nonclinical pregnancy group included 818 cycles. There were significant differences in female age (P<0.01), infertility type (P=0.04), baseline follicle-stimulating hormone level (P=0.04), anti-Müllerian hormone (AMH) level (P<0.01), antral follicle count (P<0.01), number of transferred embryos (P=0.045) and type of transferred embryo (P<0.01). There was no significant difference in the mean bilateral PI (1.98 ± 0.34 vs. 1.95 ± 0.35, P=0.10). The multivariate analysis results showed that maternal age (AOR=0.95, 95% CI=0.93-0.98, P<0.01), AMH level (AOR=1.00, 95% CI=1.00-1.01, P=0.045), number of transferred embryos (AOR=1.98, 95% CI=1.47-2.70, P<0.01), and type of transferred embryo (AOR=3.10, 95% CI=2.27-4.23, P<0.01) were independent factors influencing the clinical pregnancy rate. The mean PI (AOR=0.85, 95% CI=0.70-1.05; P=0.13) was not an independent factor influencing the clinical pregnancy rate. Participants were divided into two groups according to the mean PI cutoff value of 1.75, and there was no significant difference between the two groups (P > 0.05). In this study, we found that the uterine artery PI on the day of endometrial transformation in patients undergoing FET is not a good predictor of pregnancy outcomes.