Uteroplacental Blood Flow Research Articles

Seasonal and temporal variation in the placenta during melatonin supplementation in a bovine compromised pregnancy model.

Compromised pregnancies result in a poorly functioning placenta restricting the amount of oxygen and nutrient supply to the fetus resulting in intrauterine growth restriction (IUGR). Supplementing dietary melatonin during a compromised pregnancy increased uteroplacental blood flow and prevented IUGR in a seasonal-dependent manner. The objectives were to evaluate seasonal melatonin-mediated changes in temporal alterations of the bovine placental vascularity and transcript abundance of clock genes, angiogenic factors, and nutrient sensing genes in 54 underfed pregnant Brangus heifers (Fall, n = 29; Summer, n = 25). At day 160 of gestation, heifers were assigned to treatments consisting of adequately fed (ADQ-CON; 100% NRC; n = 13), nutrient restricted (RES-CON; 60% NRC; n = 13), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL, n = 13; RES-MEL, n = 15). The animals were fed daily at 0900 hours until day 240 where Cesarean sections were performed in the morning (0500 hours) or afternoon (1300 hours) for placentome collections. In both seasons, we observed a temporal alteration of the core clock genes in the cotyledonary tissue in a season-dependent manner. In the fall, ARNTL, CLOCK, NR1D1, and RORA transcript abundance were decreased (P ≤ 0.05) in the afternoon compared to the morning; whereas in the summer, ARNTL, PER2, and RORA expression were increased (P ≤ 0.05) in the afternoon. Interestingly, in both seasons, there was a concomitant temporal increase (P ≤ 0.05) of cotyledonary blood vessel perfusion and caruncular melatonin receptor 1A transcript abundance. Melatonin supplementation did not alter the melatonin receptor 1A transcript abundance (P > 0.05), however, in the summer, melatonin supplementation increased cotyledonary VEGFA, CRY1, and RORA (P ≤ 0.05) transcript abundance. In addition, during the summer the placentomes from underfed dams had increased average capillary size and HIF1α transcript abundance compared to those adequately fed (P ≤ 0.05). In conclusion, these data indicate increased cotyledonary blood vessel size and blood distribution after feeding to better facilitate nutrient transport. Interestingly, the maternal nutritional plane appears to play a crucial role in regulating the bovine placental circadian clock. Based on these findings, the regulation of angiogenic factors and clock genes in the bovine placenta appears to be an underlying mechanism of the therapeutic effect of dietary melatonin supplementation in the summer.

O061 / #579 BURST SPINAL CORD STIMULATION IN PREGNANCY: FIRST CLINICAL EXPERIENCES: TRACK 4: GENITOURINARY NEUROMODULATION / PELVIC PAIN / NEUROMODULATION IN PREGNANCY

The safety of active SCS therapy in pregnancy is not established and is based on limited casuistic evidence1-4. We here present the first clinical data on a case series of six women treated with burst SCS during pregnancy. Additionally, we present ultrasonographic flow measurements of fetal and uteroplacental blood flow in a pregnant patient in both ON and OFF phases of burst SCS.

The role of angiotensin II and relaxin in vascular adaptation to pregnancy.

There is a pregnancy-induced vasodilation of blood vessels, which is known to have a protective effect on cardiovascular function and can be maintained postpartum. This review outlines the cardiovascular changes that occur in a healthy human and rodent pregnancy, as well as different pathways that are activated by angiotensin II and relaxin that result in blood vessel dilation. During pregnancy, systemic and uteroplacental blood flow increase to ensure an adequate blood supply that carries oxygen and nutrients from the mother to the fetus. This results in changes to the function of the maternal cardiovascular system. There is also a pregnancy-induced vasodilation of blood vessels, which is known to have a protective effect on cardiovascular health/function. Additionally, there is evidence that the effects of maternal vascular vasodilation are maintained post-partum, which may reduce the risk of developing high blood pressure in the next pregnancy and reduce cardiovascular risk later in life. At both non-pregnant and pregnant stages, vascular endothelial cells produce a number of vasodilators and vasoconstrictors, which transduce signals to the contractile vascular smooth muscle cells to control the dilation and constriction of blood vessels. These vascular cells are also targets of other vasoactive factors, including angiotensin II (Ang II) and relaxin. The binding of Ang II to its receptors activates different pathways to regulate the blood vessel vasoconstriction/vasodilation, and relaxin can interact with some of these pathways to induce vasodilation. Based on the available literature, this review outlines the cardiovascular changes that occur in a healthy human pregnancy, supplemented by studies in rodents. A specific focus is placed on vasodilation of blood vessels during pregnancy; the role of endothelial cells and endothelium-derived vasodilators will also be discussed. Additionally, different pathways that are activated by Ang II and relaxin that result in blood vessel dilation will also be reviewed.

Transcranial focused ultrasound as a treatment for hypertension

Pharmaceuticals currently used for reducing blood pressure prove ineffective for many patients. As well, although hypertension is the most common disorder in pregnancy, many anti-hypertension drugs pose significant risks associated with restricted fetal growth, decreased uteroplacental blood flow, and fetal loss. Deep brain stimulation of the periaqueductal gray (PAG) region has shown promise in treating drug-resistant hypertension in patients. However, a non-invasive approach would carry far fewer risks, particularly during pregnancy. Our work has explored the potential of focused ultrasound (FUS), targeted to the PAG region, to reduce blood pressure. In a rodent model of hypertension, FUS delivered to the PAG successfully reduced high blood pressure to within the normal range. By comparing treatment regimes, we have also investigated the mechanisms underlying this reduction in blood pressure and ways to prolong the effect. This approach could point towards a new treatment for hypertension that has greater safety and broader applicability for vulnerable patient populations.

Effect of Labetalol for Treating Patients with Pregnancy-Induced Hypertension

Pregnancy-induced hypertension (PIH) is one of the main causes of maternal mortality. Many first- and second-line drugs are available to treat the condition. Labetalol lowers blood pressure by blocking both α and β adrenergic receptors. It preserves uteroplacental blood flow efficiently. A systemic review was carried out to find the efficacy and safety of labetalol in the treatment of PIH. Three thousand twenty-six studies were retrieved in 20 years. Finally, 28 studies were selected after applying the review criteria. Twenty-three studies detected that labetalol had superior or similar action compared to other drugs in controlling hypertension in patients with preeclampsia and eclampsia. The systematic review concluded that labetalol is a safe, effective, first-choice of drug with few side effects in treating PIH.

Molecular Development of Placenta and Its Relationship with Preeclampsia and Fetal Growth Restriction

Preeclampsia (PE) is the leading causes of maternal death worldwide as well as a significant cause of fetal morbidity and mortality, including fetal growth restriction (FGR). The concept that PE and FGR shared a common etiology is widely accepted, i.e., the maladaptive response to the impaired placentation. Normal placentation is the result of dynamic integration of cell proliferation, differentiation, and migration, in which trophoblast cells play a crucial role. Impaired trophoblast invasion into the maternal decidua leads to a decrease in uteroplacental blood flow and changes in intervillous hemodynamic. The dynamic interaction of these process with maladaptive decidual immune response, impaired cytokines and angiogenic factors regulation, and oxidative stress will lead into the clinical manifestation of PE and/or FGR.

Placental dysfunction in women at risk and threat of premature delivery

Premature birth remains one of the most urgent problems of modern obstetrics. It is not possible to reliably establish the cause in 70–80% of premature births, so the search for risk factors and markers of premature termination of pregnancy is justified. According to many authors, 25–30% of women at risk of premature birth have placental dysfunction.The objective: was to assess the prevalence of placental dysfunction in women at risk of preterm birth and with preterm birth.Materials and methods. 80 pregnant women were under observation. The criteria for inclusion in the study were the presence of risk factors for premature birth – Group I (30 women) or the threat of premature birth – Group II (30 women). The control group consisted of 20 conditionally healthy pregnant women. Transabdominal ultrasound examination with color Doppler mapping, determination of free estriol, progesterone and placental lactogen levels in blood serum was performed at 18–21+6 and 28–30 weeks of gestation.Results. The average age of the patients was 31.4±2.5 years, there was no significant difference in age, life history, social status, somatic pathology between the formed groups. Pregnant women of groups I and II probably had a history of pelvic inflammatory disease more often than in controls; colpitis; sexually transmitted infections; pathology of the cervix and operations on the uterus and appendages. The course of this pregnancy in most of the women of the studied cohort was complicated by the threat of termination of pregnancy, 36.7% of pregnant women of the I group and 46.7% of the II group had premature births. Signs of premature ripening of the placenta were detected in 13 (43.3%) pregnant women of the experimental cohort and in 1 (5.0%) of the control group (Р<0.0001), which was accompanied by changes in parameters during dopplerometry of utero-placental blood flow. Clinical manifestations of placental dysfunction occurred in 36.7% of patients in the risk group of premature birth and pregnant women with a threat of premature birth, and were manifested by a decrease in the level of progesterone, a plateau in the increase in the level of placental lactogen. Morphological signs of placental dysfunction were found in 43.3% of cases of premature birth, which correlates with the frequency of early complications of pregnancy, primarily with the formation of retrochorial hematoma.Conclusions. Clinical manifestations of placental dysfunction (fetal growth retardation, preeclampsia) occur in a third of patients of the risk group and pregnant women with a threat of premature birth, which correlates with changes in the hormone-producing function of the placenta.

DOPPLER ASSESSMENT OF UTERO-PLACENTAL HEMODYNAMICS IN PREGNANT WOMEN WITH A HISTORY OF CORONAVIRUS DISEASE (COVID-19)

The latest viral disease, which continues to spread today, is caused by a new coronavirus and poses a serious threat to public health around the world. To date, the effects of COVID-19 on pregnant women and infants have not been fully studied and remain a key area of interest. The study aimed to assess utero-placental circulation using Doppler ultrasound for pregnant women with a case history of coronavirus disease (COVID-19). A Doppler screening of utero-placental hemodynamics was performed for 156 pregnant women at 18-22 weeks. Of those, 75 pregnant women with a case history of coronavirus disease COVID-19 were in the first trimester of pregnancy. An abnormal blood flow was observed within the experimental group in 14 cases (18.6%). The analysis of spectrograms revealed the unevenness of the diastolic component with the formation of a dicrotic notch in the early diastolic phase in 5 cases (6.6%). In comparison with the control group, pregnant women with COVID-19 were twice as likely to have impaired blood flow in the uterine arteries. Uterine artery doppler measurement is really important for predicting adverse pregnancy outcomes and perinatal losses. Doppler indices of utero-placental blood flow have clinical value for pregnant women who have recovered from COVID-19.

Effect of pentaerythritol tetranitrate (PETN) on the development of fetal growth restriction in pregnancies with impaired uteroplacental perfusion at midgestation—a randomized trial

Fetal growth restriction is strongly associated with impaired placentation and abnormal uteroplacental blood flow. Nitric oxide donors such as pentaerythritol tetranitrate are strong vasodilators and protect the endothelium. Recently, we demonstrated in a randomized controlled pilot study a 38% relative risk reduction for the development of fetal growth restriction or perinatal death following administration of pentaerythritol tetranitrate to pregnant women at risk, identified by impaired uterine perfusion at midgestation. Results of this monocenter study prompted the hypothesis that pentaerythritol tetranitrate might have an effect in pregnancies with compromised placental function as a secondary prophylaxis. This study aimed to test the hypothesis that the nitric oxide donor pentaerythritol tetranitrate reduces fetal growth restriction and perinatal death in pregnant women with impaired placental perfusion at midgestation in a multicenter trial. In this multicenter, randomized, double-blind, placebo-controlled trial, 2 parallel groups of pregnant women presenting with a mean uterine artery pulsatility index >95th percentile at 19+0 to 22+6 weeks of gestation were randomized to 50-mg Pentalong or placebo twice daily. Participants were assigned to high- or low-risk groups according to their medical history before randomization was performed block-wise with a fixed block length stratified by center and risk group. The primary efficacy endpoint was the composite outcome of perinatal death or development of fetal growth restriction. Secondary endpoints were neonatal and maternal outcome parameters. Between August 2017 and March 2020, 317 participants were included in the study and 307 were analyzed. The cumulative incidence of the primary outcome was 41.1% in the pentaerythritol tetranitrate group and 45.5% in the placebo group (unadjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; adjusted relative risk, 0.90; 95% confidence interval, 0.69-1.17; P=.43). Secondary outcomes such as preterm birth (unadjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; adjusted relative risk, 0.73; 95% confidence interval, 0.56-0.94; P=.01) and pregnancy-induced hypertension (unadjusted relative risk, 0.65; 95% confidence interval, 0.46-0.93; adjusted relative risk, 0.65; 95% confidence interval, 0.46-0.92; P=0.01) were reduced. Our study failed to show an impact of pentaerythritol tetranitrate on the development of fetal growth restriction and perinatal death in pregnant women with impaired uterine perfusion at midgestation. Pentaerythritol tetranitrate significantly reduced secondary outcome parameters such as the incidence of preterm birth and pregnancy-induced hypertension in these pregnancies.

Influence of Timing of Intravenous Fluid Therapy on Maternal Hemodynamics in Patients Undergoing Caesarean Section under Subarachnoid Block

BACKGROUND
 Subarachnoid block (SAB) is the most common technique used for caesarean sections. The main objective is the maintenance of maternal cardiac output and uteroplacental blood flow. Protocols that aim to prevent hypotension during SAB for LSCS result in a better outcome than those designed to treat. The time interval between the start of fluids and SAB determines the volume of fluid needed to combat hypotension. The objective of our research was to study the influence of the timing of IV fluid therapy on maternal hemodynamics.
 METHODS
 This prospective observational study was conducted in a tertiary hospital over 3 years. 254 patients were grouped into 3 groups as follows: patients receiving fluid predominantly before SAB (Gr P), predominantly after SAB (Gr C), and near equal amounts before and after SAB (Gr E). Patients were analyzed according to the timing and average volume of fluid they received and co-related with their intraoperative hemodynamic changes. Quantitative variables in both groups were expressed as mean ± SD and compared using unpaired t-tests between groups and paired t-tests within each group. Qualitative variables were expressed as frequencies/percentages and compared using the chi-square test. A p-value of >=0.005 was considered statistically significant. Statistical Package for Social sciences (SPSS) version 15.0 was used for statistical analysis.
 RESULTS
 Demographic data were comparable. Systolic blood pressure in all the groups showed a declining trend after SAB. However, the degree of fall was significantly higher in Gr P as compared to Gr C and Gr E. Hypotension occurred in 69 % of patients in Gr P as compared to 4.5 % in Gr C and 25 % in Gr E. Incidence of vasopressor requirement and nausea-vomiting was higher in Gr P (60.3 %). No difference in neonatal APGAR and mean total amount of IV fluid used was noted.
 CONCLUSIONS
 In conclusion, co-loading using crystalloids results in lesser hemodynamic changes, lesser incidence of nausea and vomiting and lesser requirement of vasopressors. Also, the practice of co-loading can shorten the preparation time and avoid any delays.

ACTIVITY OF NITRO-OXIDATIVE PROCESSES IN PREGNANT WOMEN WITH IDIOPATHIC ARTERIAL HYPOTENSION

Primary violation of vascular tone and reactivity is considered the main hemodynamic link in the pathogenesis of idiopathic arterial hypotension (IAH). Two gaseous messengers - nitric oxide (NO) and hydrogen sulfide (H2S) play an important role in the regulation of vascular tone.
 The research aims at determining the state of the NO system and the level of H2S in women with IAH and their effect on the uteroplacental blood flow.
 Material and Methods. A number of 20 pregnant women with IAH at 40-41 weeks of gestation were examined (group I); the second group included 20 pregnant women with normotony at 39-40 weeks of gestation. The concentration of the complex of nitrates and nitrites was determined by the reaction of formation of a colored complex by Griss reagent. The content and production of peroxynitrite in alkali and alkaline earth metals were determined according to the procedure described by Vanuffelen et al. Detection of hydrogen sulfide content in blood plasma was performed by the method of Dombkowski et al. Studies of uteroplacental blood flow were performed on ultrasonic diagnostic device "SA-8000 EX" using color Doppler mapping and pulse mapping dopplerometry of the blood flow in the uterine arteries (UA). The assessment of blood flow velocity curves was carried out by determining the pulsation index (PI) in both arteries taking into account the average value.
 Results. The results of the study showed that an average level of nitrites and nitrates in pregnant women with IAH was 37.0% higher than in women with normotension, and peroxynitrite values were 2.4 times higher, respectively. In contrast, the concentration of H2S in pregnant women with IAH was almost 1.4 times lower, than in pregnant women with normal blood pressure. Doppler study of blood flow indices in UA showed a moderate increase in PI in 28.0% of pregnant women with IAH. Thus, indices of vascular resistance in UA of pregnant women with IAH were higher, on average, by 19.0% than in pregnant women with normotension.
 Conclusions. High levels of nitrites and nitrates in pregnant women with IAH form the basis for the development of nitrosatous stress, which is accompanied by increasing concentration of highly toxic peroxynitrite. Significant increase in peroxynitrite is one of the causes of endothelial dysfunction. In pregnant women with IAH due to the low content of H2S - its vasoconstrictive effects are prevalent, which may indicate an indirect interaction between both of these systems of vasoregulation.

Burst Spinal Cord Stimulation in Pregnancy: First Clinical Experiences

ObjectivesSpinal cord stimulation (SCS) is a treatment for chronic neuropathic pain. It is based on the delivery of electric impulses to the spinal cord, traditionally in a regular square-wave pattern (“tonic” stimulation) and, more recently, in a rhythmic train-of-five “BurstDR” pattern. The safety of active SCS therapy in pregnancy is not established, and recommendations are based on limited casuistic evidence. We present in this study clinical data on a case series of six women treated with burst SCS during pregnancy. In addition, we present the ultrasonographic flow measurements of fetal and uteroplacental blood flow in a pregnant patient. Materials and MethodsPatients were included if they had been implanted with a full SCS system at Aarhus University Hospital, Denmark, between 2006 and 2020 and received active burst SCS stimulation during a pregnancy. Telephone interviews were conducted, including details on SCS therapy, medication, pregnancy course and outcome, and health status of the offspring. In one patient, the uteroplacental and fetal blood flow was assessed in gestational week 29 by Doppler flow measurements performed during both ON and OFF phases of the SCS system. ResultsSix patients were included with a total of 11 pregnancies. Three pregnancies ended in miscarriages, all in the same patient who had preexisting significant risk factors for miscarriage. Eight resulted in a live-born child with normal birth weight for gestational age; seven were born at term, and one was born late preterm, in gestational week 36. Ultrasonographic Doppler flow, measured in one patient, was normal and did not reveal any immediate changes between burst SCS ON and OFF. Seven children were reported healthy with normal neurodevelopment and one physically healthy but with developmental delays. ConclusionsThe data presented in this study add to the accumulating evidence of the safety of SCS in pregnancy.

Evaluation of the hemostasis system in pregnant women with placental dysfunction by the method of rotational thromboelastometry

The objective: to evaluate the standard indicators of thromboelastometry in pregnant women with placental dysfunction. Materials and methods. Venous blood samples of 26 healthy pregnant women (control group) and 50 patients with placental dysfunction (main group, persons 19–40 years old) were examined. The average gestation period at the time of the study was 29.5±7.2 and 32.9±4.4 weeks, respectively. Standard coagulation tests (coagulogram) and rotational thromboelastometry were performed. Results. Hypercoagulability according to the standard coagulation tests in the women with placental disorders did not correspond to gestational age. No correlation was established between coagulogram parameters, the number of platelets and temogram parameters. According to thromboelastography tests, an increase in clot density is typical for pregnant women with placental dysfunction. Specifically, the results of the fibtem test demonstrated, a statistically significant (p<0.05) increase in clot density at 5, 10, and 20 minutes. Such indicators of fibrinogen synthesis and the fibrin polymerization process indicate the formation of a denser clot in the patients with placental dysfunction. In addition, the MCF indicator, which informs about the maximum density of the clot, is significantly higher in the pregnant women with placental dysfunction compared to the control group. Conclusions. Disorders of coagulation homeostasis in the form of clot formation of increased density play an important role in the pathogenesis of placental dysfunction. This is one of the causes of hemodynamic disorders in the utero-placental and feto-placental blood flow. Thromboelastography, in contrast to the basic coagulation tests of the standard coagulogram, is a more informative method of assessment the coagulation ability of blood in the pregnant women with placental dysfunction.

G-Protein-Coupled Estrogen Receptor Expression in Rat Uterine Artery Is Increased by Pregnancy and Induces Dilation in a Ca2+ and ERK1/2 Dependent Manner.

Increasing levels of estrogens across gestation are partly responsible for the physiological adaptations of the maternal vasculature to pregnancy. The G protein-coupled estrogen receptor (GPER) mediates acute vasorelaxing effects in the uterine vasculature, which may contribute to the regulation of uteroplacental blood flow. The aim of this study was to investigate whether GPER expression and vasorelaxation may occur following pregnancy. Elucidation of the functional signalling involved was also investigated. Radial uterine and third-order mesenteric arteries were isolated from non-pregnant (NP) and pregnant rats (P). GPER mRNA levels were determined and—concentration–response curve to the GPER-specific agonist, G1 (10−10–10−6 M), was assessed in arteries pre-constricted with phenylephrine. In uterine arteries, GPER mRNA expression was significantly increased and vasorelaxation to G1 was significantly enhanced in P compared with NP rats. Meanwhile, in mesenteric arteries, there was a similar order of magnitude in NP and P rats. Inhibition of L-type calcium channels and extracellular signal-regulated kinases 1/2 significantly reduced vasorelaxation triggered by G1 in uterine arteries. Increased GPER expression and GPER-mediated vasorelaxation are associated with the advancement of gestation in uterine arteries. The modulation of GPER is exclusive to uterine arteries, thus suggesting a physiological contribution of GPER toward the regulation of uteroplacental blood flow during pregnancy.

Why are CGRP monoclonal antibodies not yet the first line treatment in migraine prevention?

Migraine is a prevalent disorder and a cause of high disability, influenced by modifiable and non-modifiable risk factors. Comorbid and psychiatric illnesses are prevalent in migraine patients and should be considered when choosing preventive drugs. There have been unforeseen problems with the use of preventive treatment of migraine with oral drugs, mainly due to side-effects that cannot be tolerated and lack of efficacy, leading to high discontinuation rates. Anti-CGRP monoclonal antibodies (mAbs) have shown better tolerance profiles, based on the low dropout rates in clinical trials due to adverse events. First-line therapy is a term most expressed in some medical specialties that adopt standardized protocol treatments and may not be suitable for treating migraine. Regarding efficacy, mAbs don't seem to perform much better than the current prophylactic oral drugs in reduction of monthly migraine days compared to placebo. Monoclonal antibodies against CGRP pathway have been prescribed recently, which raises some concern about their safety in the long term. Only side effects observation will confirm whether CGRP blockade causes susceptibility to severe side-effects, at least to specific subpopulations. CGRP may play a role in regulating uteroplacental blood flow and myometrial and uterine relaxation, as well as blood pressure control, raising the suspicion that its blockade could cause complications during pregnancy. Recent guidelines retain the recommendation of starting preventive treatment of migraine with oral drugs. Both the fact that it is new and costs are the reason why guidelines recommend the prescription of mAbs only after failure of at least two oral drugs.

AT2R activation increases in vitro angiogenesis in pregnant human uterine artery endothelial cells.

Angiogenesis is vital during pregnancy for remodeling and enhancing vasodilation of maternal uterine arteries, and increasing uterine blood flow. Abnormal angiogenesis is associated with decreased uteroplacental blood flow and development of pregnancy disorders such as gestational hypertension, preeclampsia, fetal growth restriction, preterm delivery, stillbirth, and miscarriage. The mechanisms that contribute to normal angiogenesis remain obscure. Our previous studies demonstrated that expression of the angiotensin type 2 receptor (AT2R) is increased while the angiotensin type 1 receptor (AT1R) is unchanged in the endothelium of uterine arteries, and that AT2R-mediated pregnancy adaptation facilitates enhanced vasodilation and uterine arterial blood flow. However, the role of AT2R in regulating angiogenesis during pregnancy has never been studied. This study examines whether or not AT2R activation induces angiogenesis and, if so, what mechanisms are involved. To this end, we used primary human uterine artery endothelial cells (hUAECs) isolated from pregnant and nonpregnant women undergoing hysterectomy. The present study shows that Compound 21, a selective AT2R agonist, induced proliferation of pregnant-hUAECs, but not nonpregnant-hUAECs, in a concentration-dependent manner, and that this C21-induced mitogenic effect was blocked by PD123319, a selective AT2R antagonist. The mitogenic effects induced by C21 were inhibited by blocking JNK—but not ERK, PI3K, and p38—signaling pathways. In addition, C21 concentration dependently increased cell migration and capillary-like tube formation in pregnant-hUAECs. The membrane-based antibody array showed that C21 increased expression of multiple angiogenic proteins, including EGF, bFGF, leptin, PLGF, IGF-1, and angiopoietins. Our qPCR analysis demonstrates that C21-induced increase in expression of these angiogenic proteins correlates with a proportional increase in mRNA expression, indicating that AT2R activates angiogenic proteins at the transcriptional level. In summary, the present study shows that AT2R activation induces angiogenesis of hUAECs in a pregnancy-specific manner through JNK-mediated pathways with associated transcriptional upregulation of multiple proangiogenic proteins.

Disturbance of utero-placental-fetus blood flow in pregnant women with community-acquired pneumonia of bacterial and viral (COVID-19) etiology

Introduction. Placental insufficiency is one of the most frequently developing complications in pregnant women with acute respiratory failure, which is a consequence of community-acquired pneumonia (CAP), including viral etiology. The impact of COVID-19 infection on the course of pregnancy, the condition of the fetus and newborns has not been studied enough. Aim. To study the state of uteroplacental-fetal circulation, placenta and fetus in women with bacterial and COVID-19-associated CAP in the second and third trimesters of pregnancy. Materials and methods. The history of childbirth and the results of examinations of 120 women in the second and third trimesters of pregnancy were analyzed, including 37 women with moderate CAP of bacterial etiology, 48 women with COVID-19 infection. The comparison group consisted of 35 women with uncomplicated pregnancy. The state of the placenta and fetus was assessed according to the data of ultrasound and utero-placental-fetal blood flow – Doppler study. Pulsation indices (PI) and cerebro-placental ratio (CPR) were analyzed. Results. According to our data, the risk of developing chronic placental insufficiency in pregnant women with COVID-19-associated CAP of moderate severity was higher than in groups of women with CAP of bacterial etiology and in the comparison group. In groups with CAP, significant differences were found in the indices of CPR, PI of the uterine arteries, umbilical cord arteries and middle cerebral artery, corresponding to I (A, B) or II degree of disturbance of the uteroplacental and/or placental-fetal blood flow. Chronic intrauterine fetal hypoxia and fetal growth retardation were more frequently detected in the group with COVID-19-associated CAP. Newborns born to mothers with COVID-19 infection have an increased risk of neonatal damage to the central nervous system (CNS). Conclusion. COVID-19-associated CAP, compared with CAP of bacterial etiology, increases the risk of chronic placental insufficiency, intrauterine fetal hypoxia and fetal growth retardation, and the development of neonatal CNS damage.

Compare the Histological Features between the Normal and Hypertensive Placenta

Objective: The purpose of the current research was to investigate the morphology and histology of placentas collected from moms who had PIH and to compare those results to placentas taken from women who had normal pregnancies. Study Design: The study was conducted at Anatomy department of Women Medical and Dental College Hospital Abbottabad and Mohi-ud-Din Islamic Medical College, Mirpur, AJK during the period from February 2021 to July 2021. Place and Duration: Observational/comparative study Methods: In this study total 80 pregnancies, 40 normal placenta’s and 40 hypertensive placenta’s were presented. At first, the physical aspects of placentas, also known as their morphological traits, were noted. In order to investigate the histology, pieces of each placenta measuring 5 millimetres in thickness were removed. After this, the tissue underwent further histological processing, after which it was fixed in formal saline at a concentration of 10 percent. It was noted down how much newborns weighed at birth. SPSS 23.0 was used to analyze complete data. Results: Placental weight, size, surface area and number of cotyledons were decreased in hypertensive placentas, whereas regions of infarction, retroplacental clot, and calcification were increased. Hyalinized villi and atherosclerosis have been reported in hypertensive placentas (p0.05). Foetal mortality and morbidity were closely linked to these alterations. We also found that among women with high blood pressure who had the aforementioned histological alterations in their placentas, the risk of foetal death and morbidity was higher. Conclusion: We concluded that, PIH reduces placenta weight and size. Changes in utero-placental blood flow may induce placental insufficiency. It affects newborn birth weight. PIH impacts placenta shape, histology, and foetal development. Keywords: Placenta, Pregnancy-induced hypertension, Histological, Morphological, Mortality, Morbidity

A Review of Nanotechnology for Treating Dysfunctional Placenta.

The placenta plays a significant role during pregnancy. Placental dysfunction contributes to major obstetric complications, such as fetal growth restriction and preeclampsia. Currently, there is no effective treatment for placental dysfunction in the perinatal period, and prophylaxis is often delivered too late, at which point the disease manifestation cannot be prevented. However, with recent integration of nanoscience and medicine to perform elaborate experiments on the human placenta, it is expected that novel and efficient nanotherapies will be developed to resolve the challenge of managing placental dysfunction. The advent of nanomedicine has enabled the safe and targeted delivery of drugs using nanoparticles. These smart nanoparticles can load the necessary therapeutic substances that specifically target the placenta, such as drugs, targeting molecules, and ligands. Packaging multifunctional molecules into specific delivery systems with high targeting ability, diagnosis, and treatment has emerged as a novel theragnostic (both therapeutic and diagnostic) approach. In this review, the authors discuss recent advances in nanotechnology for placental dysfunction treatment. In particular, the authors highlight potential candidate nanoparticle-loaded molecules that target the placenta to improve utero-placental blood flow, and reduce reactive oxygen species and oxidative stress. The authors intend to provide basic insight and understanding of placental dysfunction, potential delivery targets, and recent research on placenta-targeted nanoparticle delivery systems for the potential treatment of placental dysfunction. The authors hope that this review will sensitize the reader for continued exploration of novel nanomedicines.

Major intraoperative bleeding and drastic change in circulatory dynamics in a pregnant patient with metastatic pheochromocytoma: a case report

BackgroundMetastatic pheochromocytoma in the spine is a very rare complication during pregnancy. We report anesthesia in a pregnant woman for resection of an undiagnosed spinal tumor, accompanied by remarkable hemodynamic changes and massive bleeding.Case presentationA 33-year-old woman at 17 weeks of gestation presented with the rapid progress of bilateral lower leg paralysis. A diagnosis of spinal tumor was made, and surgical resection was planned. Although the surgery was suspended because of remarkable hemodynamic changes and massive bleeding, fetal heart rate was stable. Postoperative examination revealed pheochromocytoma in the urinary bladder as a primary lesion with spinal metastasis.ConclusionAlthough spinal pheochromocytoma is extremely rare in pregnant women, it should be suspected when abnormal hypertension is observed with accompanying neurological deficits. Preservation of maternal circulation and uteroplacental blood flow should be the first priority during anesthesia.