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Biology of Sex Differences Jun 2024Prenatal hypoxia, a common pregnancy complication, leads to impaired cardiovascular outcomes in the adult offspring. It results in impaired vasodilation in coronary and...
BACKGROUND
Prenatal hypoxia, a common pregnancy complication, leads to impaired cardiovascular outcomes in the adult offspring. It results in impaired vasodilation in coronary and mesenteric arteries of the adult offspring, due to reduced nitric oxide (NO). Thromboxane A (TxA) is a potent vasoconstrictor increased in cardiovascular diseases, but its role in the impact of prenatal hypoxia is unknown. To prevent the risk of cardiovascular disease by prenatal hypoxia, we have tested a maternal treatment using a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ). We hypothesized that prenatal hypoxia enhances vascular TxA responses in the adult offspring, due to decreased NO modulation, and that this might be prevented by maternal nMitoQ treatment.
METHODS
Pregnant Sprague-Dawley rats received a single intravenous injection (100 µL) of vehicle (saline) or nMitoQ (125 µmol/L) on gestational day (GD)15 and were exposed to normoxia (21% O) or hypoxia (11% O) from GD15 to GD21 (term = 22 days). Coronary and mesenteric arteries were isolated from the 4-month-old female and male offspring, and vasoconstriction responses to U46619 (TxA analog) were evaluated using wire myography. In mesenteric arteries, L-NAME (pan-NO synthase (NOS) inhibitor) was used to assess NO modulation. Mesenteric artery endothelial (e)NOS, and TxA receptor expression, superoxide, and 3-nitrotyrosine levels were assessed by immunofluorescence.
RESULTS
Prenatal hypoxia resulted in increased U46619 responsiveness in coronary and mesenteric arteries of the female offspring, and to a lesser extent in the male offspring, which was prevented by nMitoQ. In females, there was a reduced impact of L-NAME in mesenteric arteries of the prenatal hypoxia saline-treated females, and reduced 3-nitrotyrosine levels. In males, L-NAME increased U46619 responses in mesenteric artery to a similar extent, but TxA receptor expression was increased by prenatal hypoxia. There were no changes in eNOS or superoxide levels.
CONCLUSIONS
Prenatal hypoxia increased TxA vasoconstrictor capacity in the adult offspring in a sex-specific manner, via reduced NO modulation in females and increased TP expression in males. Maternal placental antioxidant treatment prevented the impact of prenatal hypoxia. These findings increase our understanding of how complicated pregnancies can lead to a sex difference in the programming of cardiovascular disease in the adult offspring.
Topics: Animals; Female; Rats, Sprague-Dawley; Pregnancy; Vasoconstriction; Male; Prenatal Exposure Delayed Effects; Thromboxane A2; Sex Characteristics; Antioxidants; Nitric Oxide; Mesenteric Arteries; Rats; Hypoxia; Fetal Hypoxia; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
PubMed: 38898532
DOI: 10.1186/s13293-024-00627-x -
Obstetrical & Gynecological Survey Jun 2024Placenta accreta spectrum (PAS) represents a range of disorders characterized by abnormal placental invasion and is associated with severe maternal morbidity and... (Review)
Review
IMPORTANCE
Placenta accreta spectrum (PAS) represents a range of disorders characterized by abnormal placental invasion and is associated with severe maternal morbidity and mortality.
OBJECTIVE
The aim of this study was to review and compare the most recently published major guidelines on the diagnosis and management of this potentially life-threatening obstetric complication.
EVIDENCE ACQUISITION
A descriptive review of guidelines from the American College of Obstetricians and Gynecologists, the Royal Australian and New Zealand College of Obstetricians and Gynecologists, the International Society for Abnormally Invasive Placenta, the Royal College of Obstetricians and Gynecologists, the International Federation of Gynecology and Obstetrics, and the Society of Obstetricians and Gynecologists of Canada on PAS disorders was carried out.
RESULTS
There is a consensus among the reviewed guidelines regarding the definition and the diagnosis of PAS using specific sonographic signs. In addition, they all agree that the use of magnetic resonance imaging should be limited to the evaluation of the extension to pelvic organs in case of placenta percreta. Moreover, American College of Obstetricians and Gynecologists, Royal College of Obstetricians and Gynecologists, International Federation of Gynecology and Obstetrics, and the Society of Obstetricians and Gynecologists of Canada agree that screening for PAS disorders should be based on clinical risk factors along with sonographic findings. Regarding management, they all highlight the importance of a multidisciplinary team approach and recommend delivery by elective cesarean section at a tertiary center with experienced staff and appropriate resources. Routine preoperative ureteric stenting and occlusion of pelvic arteries are universally not recommended. Moreover, hysterectomy following the delivery of the fetus, expectant management with placenta left in situ, and conservative management in case of focal disease and desired fertility are all considered as acceptable treatment options. The reviewed guidelines also suggest some measures for intraoperative and postoperative hemorrhage control and recommend prophylactic administration of antibiotics. Methotrexate after expectant management is unanimously discouraged. On the other hand, there is no common pathway with regard to the optimal timing of delivery, the recommended mode of anesthesia, the preferred skin incision, and the effectiveness of the delayed hysterectomy approach.
CONCLUSIONS
PAS disorders are mainly iatrogenic conditions with a constantly rising incidence and potentially devastating consequences for both the mother and the neonate. Thus, the development of uniform international practice protocols for effective screening, diagnosis, and management seems of paramount importance and will hopefully drive favorable pregnancy outcomes.
Topics: Humans; Placenta Accreta; Female; Pregnancy; Practice Guidelines as Topic; Cesarean Section; Hysterectomy; Ultrasonography, Prenatal
PubMed: 38896432
DOI: 10.1097/OGX.0000000000001274 -
Frontiers in Immunology 2024IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL)....
INTRODUCTION
IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL). The biology of IL6 during IUI at the maternal-fetal interface was investigated in samples from human subjects and non-human primates (NHP).
METHODS
Pregnant women with histologic chorioamnionitis diagnosed by placenta histology were recruited (n=28 term, n=43 for preterm pregnancies from 26-36 completed weeks of gestation). IUI was induced in Rhesus macaque by intraamniotic injection of lipopolysachharide (LPS, n=23). IL1 signaling was blocked using Anakinra (human IL-1 receptor antagonist, n=13), and Tumor necrosis factor (TNF) signaling was blocked by anti TNF-antibody (Adalimumab n=14). The blockers were given before LPS. All animals including controls (intraamniotic injection of saline n=27), were delivered 16h after LPS/saline exposure at about 80% gestation.
RESULTS
IUI induced a robust expression of mRNAs in the fetal membranes (chorion-amnion-decidua tissue) both in humans (term and preterm) and NHP. The major sources of mRNA expression were the amnion mesenchymal cells (AMC) and decidua stroma cells. Additionally, during IUI in the NHP, (a protease that cleaves membrane bound IL6 receptor (IL6R) to release a soluble form) and mRNA increased in the fetal membranes, and the ratio of IL6 and soluble forms of IL6R, gp130 increased in the amniotic fluid signifying upregulation of IL6 trans-signaling. Both IL1 and TNF blockade suppressed LPS-induced mRNAs in the AMC and variably decreased elements of IL6 trans-signaling.
DISCUSSION
These data suggest that IL1 and TNF blockers may be useful anti-inflammatory agents via suppression of IL6 signaling at the maternal-fetal interface.
Topics: Female; Pregnancy; Humans; Animals; Interleukin-6; Signal Transduction; Macaca mulatta; Tumor Necrosis Factor-alpha; Chorioamnionitis; Lipopolysaccharides; Interleukin-1; Adult; Obstetric Labor, Premature; Inflammation; Interleukin 1 Receptor Antagonist Protein; Placenta
PubMed: 38895127
DOI: 10.3389/fimmu.2024.1416162 -
Journal of Clinical Medicine May 2024In light of increased cesarean section rates, the incidence of placenta accreta spectrum (PAS) disorder is increasing. Despite the establishment of clinical practice...
INTRODUCTION
In light of increased cesarean section rates, the incidence of placenta accreta spectrum (PAS) disorder is increasing. Despite the establishment of clinical practice guidelines offering recommendations for early and effective PAS diagnosis and treatment, antepartum diagnosis of PAS remains a challenge. This ultimately risks poor mental health and poor physical maternal and neonatal health outcomes.
CASE DESCRIPTIONS
This case series details the experience of two high-risk patients who remained undiagnosed for PAS until they presented with antenatal hemorrhage, leading ultimately to necessary, complex surgical interventions, which can only be optimally provide in a tertiary care center. Patient 1 is a 37-year-old woman with a history of three cesarean sections, which elevates her risk for PAS. She had placenta previa detected at 19 weeks, and placenta percreta diagnosed upon hemorrhage. During a hysterectomy, invasive placenta was found in the patient's bladder, leading to a cystotomy and right ureteric reimplantation. After discharge, she was diagnosed with a vesicovaginal fistula, and is currently awaiting surgical repair. Patient 2 is a 34-year-old woman with two previous cesarean sections. The patient had complete placenta previa detected at 19- and 32-week gestation scans. She presented with antepartum hemorrhage at 35 weeks and 2 days. An ultrasound showed thin myometrium at the scar site with significant vascularity. A hysterectomy was performed due to placental attachment issues, with significant blood loss. Both patients were at high risk for PAS based on past medical history, risk factors, and pathognomonic imaging findings.
DISCUSSION
We highlight the importance of the implementation of clinical guidelines at non-tertiary healthcare centers. We offer clinical-guideline-informed recommendations for radiologists and antenatal care providers to promote early PAS diagnosis and, ultimately, better patient and neonatal outcomes through increased access to adequate care.
PubMed: 38892867
DOI: 10.3390/jcm13113155 -
Nutrients Jun 2024The placenta is the largest fetal organ, which connects the mother to the fetus and supports most aspects of organogenesis through the transport of nutrients and gases.... (Review)
Review
Association of Placental Pathology with Physical and Neuronal Development of Infants: A Narrative Review and Reclassification of the Literature by the Consensus Statement of the Amsterdam Placental Workshop Group.
The placenta is the largest fetal organ, which connects the mother to the fetus and supports most aspects of organogenesis through the transport of nutrients and gases. However, further studies are needed to assess placental pathology as a reliable predictor of long-term physical growth or neural development in newborns. The Consensus Statement of the Amsterdam Placental Workshop Group (APWGCS) on the sampling and definition of placental lesions has resulted in diagnostic uniformity in describing the most common pathological lesions of the placenta and contributed to the international standardization of descriptions of placental pathology. In this narrative review, we reclassified descriptions of placental pathology from previously published papers according to the APWGCS criteria and comparatively assessed the relationship with infantile physical and/or neural development. After reclassification and reevaluation, placental pathology of maternal vascular malperfusion, one of the APWGCS criteria, emerged as a promising candidate as a universal predictor of negative infantile neurodevelopmental outcomes, not only in term and preterm deliveries but also in high-risk groups of very low birthweight newborns. However, there are few studies that examined placental pathology according to the full categories of APWGCS and also included low-risk general infants. It is necessary to incorporate the assessment of placental pathology utilizing APWGCS in the design of future birth cohort studies as well as in follow-up investigations of high-risk infants.
Topics: Humans; Pregnancy; Female; Placenta; Infant, Newborn; Consensus; Placenta Diseases; Child Development; Infant; Netherlands
PubMed: 38892717
DOI: 10.3390/nu16111786 -
Frontiers in Cell and Developmental... 2024Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive...
Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive health outcomes, including male and female infertility, poor-pregnancy outcomes, and increased risk of diseases in childhood and beyond. To investigate the effects of EDCs and lifestyle on all aspects of reproduction (including early oocyte development, fertilization, embryo development, embryo implantation, abortion, and preterm birth). We performed this cohort study on patients receiving fertilization (IVF) treatment. Biological samples including urine, serum, follicular fluid, semen, fetal tissue, decidua, and placenta, were obtained. By studying the correlations between reproductive outcomes and environmental pollutant exposure and lifestyle, we determined the toxicological mechanisms and health effects of EDCs on female reproductive health. We found that higher concentrations of per- and polyfluoroalkyl substances were correlated with polycystic ovary syndrome (PCOS). Using specific biomarkers, we also detected the concentrations of organophosphorus flame retardants (OPFRs) in urine and found that OPFRs may disrupt hormone homeostasis. All of these results reveal EDCs may disrupt female reproduction.
PubMed: 38887521
DOI: 10.3389/fcell.2024.1335028 -
Frontiers in Physiology 2024Intrahepatic cholestasis of pregnancy (ICP) stands as the predominant liver disorder affecting pregnant women, with a prevalence ranging from 0.2% to 15.6%. While ICP...
Intrahepatic cholestasis of pregnancy (ICP) stands as the predominant liver disorder affecting pregnant women, with a prevalence ranging from 0.2% to 15.6%. While ICP is known to heighten the chances of perinatal mortality and morbidity, its pathogenesis remains elusive, and therapeutic options are limited. The objective of this study was to explore the characteristic lipid signature in placentas collected from normal pregnancies and those with mild and severe intrahepatic cholestasis of pregnancy. This research aims to clarify the pathogenesis and identify lipid biomarker for ICP through LC-MS/MS based lipidomic analysis. Placenta samples were collected from 30 normal pregnancy women and 30 mild and severe ICP women respectively. Women with normal pregnancy and ICP were recruit from April 2021 to July 2022 in Chengdu, China. And LC-MS/MS based lipidomic analysis was used to explore the characteristic placental lipids in mild and severe ICP. Fourty-four lipids were differentially expressed both in mild and severe ICP placenta. The pathway analysis revealed these lipids are mainly enriched in glycerophospholipid metabolism and autophagy pathway. Weighted correlation network analysis (WGCNA) identified the correlation network module of lipids highly related to ICP. Using multiple logistic regression analysis, we identified three and four combined metabolites that had an area under receiver operating characteristic curves (AUC) ≥ 0.90. Our results systematically revealed the lipid signature in mild and severe ICP placenta. The results may provide new insight into the treatment and early prediction of ICP.
PubMed: 38887316
DOI: 10.3389/fphys.2024.1276722 -
Journal of Investigative Medicine High... 2024Pulmonary nodules are commonly encountered in pulmonary practice. Etiologies could include infectious, inflammatory, and malignant. Placental transmogrification of the...
Pulmonary nodules are commonly encountered in pulmonary practice. Etiologies could include infectious, inflammatory, and malignant. Placental transmogrification of the lung is an extremely rare etiology of pulmonary nodules. Such condition often presents as unilateral lesions in asymptomatic men. In general, such nodules are generally stable and grow extremely slowly. We highlight an unusual case of placental transmogrification of the lung (PLC) identified in a young female. The patient's bilateral nodules were larger than what has been previously cited in the literature and exhibited growth over an 8-year follow-up period.
Topics: Humans; Female; Tomography, X-Ray Computed; Lung; Pregnancy; Adult; Placenta; Lung Diseases; Multiple Pulmonary Nodules
PubMed: 38884539
DOI: 10.1177/23247096241261322 -
Journal of Medical Ultrasound 2024Hypertensive disorders in pregnancy account for 15%-20% maternal and 20%-25% perinatal mortality. There is interest in predicting preeclampsia (PE) early in pregnancy to...
BACKGROUND
Hypertensive disorders in pregnancy account for 15%-20% maternal and 20%-25% perinatal mortality. There is interest in predicting preeclampsia (PE) early in pregnancy to reduce PE and its subsequent complications. There is no cheap and easily available, reliable predictor for PE. Some studies have shown that the lateral location of placenta is associated with adverse pregnancy outcomes due to PE. The lateral placenta is yet to be proven as a strong predictor of PE to initiate preventive measures. Placental localization can be easily done on routine ultrasonography during pregnancy. In the light of these observations, a prospective study was done to study any association between PE and placental location by ultrasound in third trimester. Research Question: Is there any association between placental location on ultrasound and preeclampsia in third trimester? The objective is to study association between location of placenta and preeclampsia and compare placental location in normotensive pregnancies with that in PE in third trimester.
METHODS
A prospective comparative, case-control, observational study was conducted in the Department of Obstetrics and Gynecology at North DMC Medical College and Hindu Rao Hospital, Delhi, India, from August 2019 to April 2020. The study population included 200 pregnant women with singleton pregnancy in third trimester, without any medical disorders such as diabetes mellitus, hypertension, renal disease, cardiac disease, and coagulation disorder or smoking. One hundred women had preeclampsia and 100 were normotensive controls. Ultrasound was done after filling F form as per the Government of India guidelines to rule out sex determination, and placenta was localized by ultrasound. Placenta was classified as central when it was equally distributed between the right and left sides of the uterus irrespective of anterior, posterior, or fundal position and lateral when 75% or more of the placental mass was on one side of the midline. Placental location was compared in hypertensive and normotensive pregnancies.
RESULTS
Out of the total 200 women, 152 (76%) had central and 48 (24%) had lateral placenta. Ninety-two percent of controls and 60% of cases had central placenta. Forty percent of cases and only 8% normotensive women had lateral placenta. Lateral placenta was five times more frequent in presence of PE as compared to normotensive controls. Out of 152 women with central placenta, 92 (60.5%) women were normotensive but with lateral placenta, only 8 (16.7%) had normal blood pressure. PE was present in 83% of women with lateral placenta and in only 39.47% with central placenta. This difference was statistically significant as < 0.0001 as per Chi-square test. This reflects a significant association between lateral position of placenta and occurrence of PE. As per odds ratio (0.1304) patients without lateral placenta had 90% protection against preeclampsia.
CONCLUSION
Central placenta is more common than lateral placenta. Lateral placenta is seen five times more frequently among hypertensive women and this difference is statistically significant. The absence of lateral placenta provides 90% protection against PE but the severity of PE was not affected by placental location..
PubMed: 38882611
DOI: 10.4103/jmu.jmu_39_23 -
Frontiers in Cell and Developmental... 2024Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent cells that can be obtained from various tissues, such as dental pulp, adipose tissue,...
Proteomic analysis and functional validation reveal distinct therapeutic capabilities related to priming of mesenchymal stromal/stem cells with IFN-γ and hypoxia: potential implications for their clinical use.
Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent cells that can be obtained from various tissues, such as dental pulp, adipose tissue, bone marrow and placenta. MSCs have gained importance in the field of regenerative medicine because of their promising role in cell therapy and their regulatory abilities in tissue repair and regeneration. However, a better characterization of these cells and their products is necessary to further potentiate their clinical application. In this study, we used unbiased high-resolution mass spectrometry-based proteomic analysis to investigate the impact of distinct priming strategies, such as hypoxia and IFN-γ treatment, on the composition and therapeutic functionality of the secretome produced by MSCs derived from the amniotic membrane of the human placenta (hAMSCs). Our investigation revealed that both types of priming improved the therapeutic efficacy of hAMSCs, and these improvements were related to the secretion of functional factors present in the conditioned medium (CM) and exosomes (EXOs), which play crucial roles in mediating the paracrine effects of MSCs. In particular, hypoxia was able to induce a pro-angiogenic, innate immune response-activating, and tissue-regenerative hAMSC phenotype, as highlighted by the elevated production of regulatory factors such as VEGFA, PDGFRB, ANGPTL4, ENG, GRO-γ, IL8, and GRO-α. IFN-γ priming, instead, led to an immunosuppressive profile in hAMSCs, as indicated by increased levels of TGFB1, ANXA1, THBS1, HOMER2, GRN, TOLLIP and MCP-1. Functional assays validated the increased angiogenic properties of hypoxic hAMSCs and the enhanced immunosuppressive activity of IFN-γ-treated hAMSCs. This study extends beyond the direct priming effects on hAMSCs, demonstrating that hypoxia and IFN-γ can influence the functional characteristics of hAMSC-derived secretomes, which, in turn, orchestrate the production of functional factors by peripheral blood cells. This research provides valuable insights into the optimization of MSC-based therapies by systematically assessing and comparing the priming type-specific functional features of hAMSCs. These findings highlight new strategies for enhancing the therapeutic efficacy of MSCs, particularly in the context of multifactorial diseases, paving the way for the use of hAMSC-derived products in clinical practice.
PubMed: 38882056
DOI: 10.3389/fcell.2024.1385712