-
IMeta Apr 2024Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a... (Review)
Review
Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a unique period in a woman's lifespan, pregnancy is characterized by changes in hormones, immunity, and metabolism. The gut microbiota also changes during this period and plays a crucial role in maintaining a healthy pregnancy. Consequently, anomalies in the composition and function of the gut microbiota, namely, gut microbiota dysbiosis, can predispose individuals to various pregnancy complications, posing substantial risks to both maternal and neonatal health. However, there are still many controversies in this field, such as "sterile womb" versus "in utero colonization." Therefore, a thorough understanding of the roles and mechanisms of gut microbiota in pregnancy and its complications is essential to safeguard the health of both mother and child. This review provides a comprehensive overview of the changes in gut microbiota during pregnancy, its abnormalities in common pregnancy complications, and potential etiological implications. It also explores the potential of gut microbiota in diagnosing and treating pregnancy complications and examines the possibility of gut-derived bacteria residing in the uterus/placenta. Our aim is to expand knowledge in maternal and infant health from the gut microbiota perspective, aiding in developing new preventive and therapeutic strategies for pregnancy complications based on intestinal microecology.
PubMed: 38882493
DOI: 10.1002/imt2.167 -
Cureus Jun 2024Pregnancy is a highly regulated biological phenomenon that involves the development of a semi-allogeneic fetus inside the uterus of the mother. The maternal-fetal... (Review)
Review
Pregnancy is a highly regulated biological phenomenon that involves the development of a semi-allogeneic fetus inside the uterus of the mother. The maternal-fetal interface is a critical junction where communication takes place between the fetal and maternal immune systems, which determine the outcome of the pregnancy. The interface is composed of the decidua and placenta. The main cells present at the maternal-fetal interface include invading trophoblasts, maternal immune cells, and decidual stromal cells. Although maternal tolerance is crucial for maintaining a successful pregnancy, the role of the placenta in pregnancy is also important. Dysregulation of the placenta leads to various placenta-mediated complications, such as preeclampsia, intrauterine growth restriction, and placental abruption. Although the exact mechanism involving these complications is unclear, research has elucidated various factors involved in these pregnancy disorders. This review aimed to provide a summary of the maternal-fetal interface and immune mechanisms involved in placenta-mediated complications.
PubMed: 38882223
DOI: 10.7759/cureus.62457 -
Cureus Jun 2024Advances in assisted reproductive technologies have enabled postmenopausal women to achieve pregnancy beyond their reproductive lifespan. Although rare, these...
Advances in assisted reproductive technologies have enabled postmenopausal women to achieve pregnancy beyond their reproductive lifespan. Although rare, these pregnancies are challenging and require a multidisciplinary approach due to the higher prevalence of medical comorbidities in this population. The placenta accreta spectrum is characterized by an abnormal invasion of chorionic villi into the myometrium. Risk factors associated with the placenta accreta spectrum include prior uterine surgeries, advanced maternal age, multiparity, in vitro fertilization, and placenta previa. We present a case of a 59-year-old postmenopausal woman with chronic hypertension, stage II chronic kidney injury, and superimposed pre-eclampsia who underwent cesarean delivery complicated by suspected focal placenta accreta. Histopathological examination revealed significant deviations from normative placental architecture, emphasizing the invasion of the villi. Further, congested blood vessels and the presence of inflammatory cells, along with heightened collagen deposition, suggest an underlying pathological process affecting placental health. These findings underscore a perturbation of placental homeostasis, emphasizing the necessity for further investigation into the mechanisms contributing to placental pathology in postmenopausal pregnancies.
PubMed: 38882221
DOI: 10.7759/cureus.62332 -
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 -
PeerJ 2024COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the...
BACKGROUND
COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia.
METHODS
Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed.
RESULTS
The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53-43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52-38.4]). Comorbidities were more frequent in the PE+ group (63.6% 31.5%, = 0.03), as well as prematurity (81.8% 41.6%, = 0.02), low birth weight (63.6% 24.7%, = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% 27.0%, = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34-4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant.
CONCLUSIONS
Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; COVID-19; Brazil; Prospective Studies; Adult; Tertiary Care Centers; Pregnancy Complications, Infectious; Risk Factors; Pregnancy Outcome; Prevalence; SARS-CoV-2; Infant, Newborn; Fetal Growth Retardation; Comorbidity
PubMed: 38881857
DOI: 10.7717/peerj.17481 -
International Journal of Cardiology Jun 2024The purpose of this study was to analyse the association between stannum exposure during pregnancy and congenital heart diseases in offspring.
BACKGROUND
The purpose of this study was to analyse the association between stannum exposure during pregnancy and congenital heart diseases in offspring.
METHODS
Based on a prospective birth cohort study conducted in Gansu Maternal and Child Health Hospital from 2010 to 2012, 14,359 pregnant women were followed up using a nested case-control study method. 97 pregnant women whose offspring were diagnosed with CHDs were used as the case group, and 194 pregnant women whose offspring did not suffer from congenital heart diseases were used as the control group in a ratio of 1:2 according to their age and place of birth. Inductively coupled plasma mass spectrometry was used to determine elemental stannum in blood samples from pregnant women hospitalized for delivery and in fetal cord blood samples. Multifactorial logistic regression analysis was used to assess the association between stannum and offspring CHDs.
RESULTS
There was a moderate positive correlation between the concentration of stannum in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood stannum level was associated with a greater risk of CHDs (aOR 3.409, 95%CI 1.785-6.826), isolated CHDs (aOR 4.044, 95%CI 1.803-9.070), multiple CHDs (aOR 2.625, 95%CI 1.137-6.061), patent ductus arteriosus (aOR 2.882, 95%CI 1.443-5.756), atrial septal defects (aOR 3.067, 95%CI 1.406-6.690), ventricular septal defects (aOR 7.414, 95%CI 1.414-38.874). There was a correlation between the maternal and cord blood sample suggesting stannum crosses the placenta.
PubMed: 38880423
DOI: 10.1016/j.ijcard.2024.132270 -
International Journal of Hygiene and... Jun 2024Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair...
BACKGROUND
Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited.
METHODS
We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture.
RESULTS
The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident.
CONCLUSION
We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.
PubMed: 38879913
DOI: 10.1016/j.ijheh.2024.114407 -
BMC Pregnancy and Childbirth Jun 2024To evaluate the potential connections between marginal cord insertion during the first trimester and furcate cord insertion later in pregnancy.
OBJECTIVES
To evaluate the potential connections between marginal cord insertion during the first trimester and furcate cord insertion later in pregnancy.
METHODS
This is a prospective study of screening data on the cord insertion site in 3178 singleton pregnancies. The cord insertion site was examined in two stages. The first stage was screening for the cord insertion site between 10-13 weeks of gestation, the purpose is to determine the category of umbilical cord insertion. The second stage, performed at 22-28 weeks of gestation, was to follow up on the relationship between the cord insertion site and the placenta and to identify any changes in the category of umbilical cord insertion. This was performed to diagnose or exclude furcate cord insertion by identifying whether the umbilical cord trunk separated or branched before it reached the placenta. Factors influencing progression to furcate cord insertion and perinatal complications were assessed.
RESULTS
Fourteen cases (0.44%) with progression to furcate cord insertion, all of which showed marginal cord insertion on ultrasound in the first trimester (p < 0.001). without progression to furcate cord insertion, there were no changes in the category of umbilical cord insertion in 3050 cases (96.40%) compared to the early pregnancy. 114 cases (3.60%) with changes in the category of umbilical cord insertion that was not consistent with furcate cord insertion. A total of 14 cases progressed to furcate cord insertion, all showed the cord insertion site were in close proximity, and 11 (78.57%) cases showed a low insertion site (p < 0.001). Regarding the choice of mode of delivery, elective caesarean delivery was done in 8/14 (57.14%). The incidences of spontaneous vaginal delivery were 5/14 (35.71%) (p < 0.001). One (7.14%) case of progression to furcate cord insertion due to haematoma at the root of the umbilical cord ended with an emergency caesarean section. In terms of perinatal complications, marginal cord insertion that progressed to furcate cord insertion had higher incidences of SGA infants, abnormal placental morphology, retention of the placenta, and cord-related adverse pregnancy outcomes than not progressed to furcate cord insertion (p < 0.05).
CONCLUSIONS
Marginal cord insertion in the first trimester has the potential to progress to furcate cord insertion. We suggest that ultrasound-diagnosed marginal cord insertion in the first trimester should be watched carefully in the second trimester, which is clinically useful to accurately determine the category of cord insertion and to improve the rate of prenatal diagnosis of furcate cord insertion.
Topics: Humans; Pregnancy; Female; Pregnancy Trimester, First; Umbilical Cord; Prospective Studies; Adult; Ultrasonography, Prenatal; Placenta; Gestational Age; Infant, Newborn
PubMed: 38879535
DOI: 10.1186/s12884-024-06562-4 -
Placenta Jun 2024Correct placental development and function are essential for adapting the mother to the ongoing pregnancy and the wellbeing of the growing fetus; however, underlying...
Correct placental development and function are essential for adapting the mother to the ongoing pregnancy and the wellbeing of the growing fetus; however, underlying processes are still poorly understood. Only limited structural and cellular placental features are shared among species hence requiring reliable human in-vitro models. Recently established trophoblast stem cell and organoid models significantly improved placental research; however, the human placenta constitutes a multi-cellular organ with tightly orchestrated, cellular and molecular networks between trophoblasts (TBs) and villous core cells (VCCs) vital for correct placentation. The establishment of co-culture models is accordingly the logical consequence to investigate TB and VCC interactions, but first requires efficient purification of ideally donor-matched placental cell types. We herein present a meticulously-tailored protocol based on four sequential digestion steps (d-steps) with varying enzyme compositions and digestion mode and length, gently releasing cells layer-by-layer from human first trimester placentae (8 - 9th week of gestation). Using immunofluorescence and flow cytometry, we analyzed the tissue fragments and digestion solutions after every d-step and collected data on individual digestion progress as well as cell viability, counts, and specifications. D-step 1 revealed a significantly low viability and was mainly composed of syncytial fragments, extravillous trophoblasts EVTs, and maternal leukocytes. D-step 2 and 3, comprising high viability predominantly contained TBs (90-99 %) with a significant enrichment of EVTs in d-step 2 and an almost pure villous cytotrophoblast (vCTB) population in d-step 3. D-step 4 finally enabled isolating fetal VCCs consisting of endothelial cells, fibroblasts, and Hofbauer cells. Interestingly, maternal leukocytes were detected in d-step 1 and 2 but completely absent from d-step 3 and 4 revealing pure fetal cell populations. In sum, we present a detailed guideline for stepwise isolating selected placental cell types suitable for further studies and co-culture models investigating TB and VCC interactions involved in early placental development.
PubMed: 38879406
DOI: 10.1016/j.placenta.2024.06.006 -
Placenta May 2024Gestational diabetes mellitus (GDM) is a major pregnancy metabolic disorder and is strongly linked with obesity. Kisspeptin is a hormone that increases several...
INTRODUCTION
Gestational diabetes mellitus (GDM) is a major pregnancy metabolic disorder and is strongly linked with obesity. Kisspeptin is a hormone that increases several thousand-fold in the maternal circulation during human pregnancy, with placenta as its main source. Studies have suggested that kisspeptin regulates trophoblast invasion and promotes pancreatic insulin secretion and peripheral insulin sensitivity.
METHODS
In a well-characterized cohort of pregnant South African women and molecular and histological techniques, this study explored the impact and interaction of maternal obesity and GDM on kisspeptin (KISS1) signalling in relation to placental morphology and maternal and neonatal parameters.
RESULTS
We found that GDM had no effect on placental KISS1 and KISS1R (KISS1 receptor) mRNA and/or protein expression. However, obesity reduced placental KISS1R mRNA expression even though overall KISS1 protein abundance or localization was not different from the non-obese group. Maternal and cord circulating KISS1 concentrations did not vary with obesity or GDM, but maternal circulating KISS1 was positively correlated with placenta weight in non-GDM obese women, and negatively correlated with placental intervillous space volume in non-GDM non-obese women. Cord serum KISS1 was positively correlated with infant weight in GDM obese women, but negatively correlated with maternal BMI in the non-obese GDM group. Placental syncytiotrophoblast extracellular vesicles exhibited detectable KISS1 and its abundance was ∼50 % lower in those from obese GDM compared to non-GDM women.
DISCUSSION
This study shows maternal obesity and GDM can modulate placental kisspeptin signalling and placental morphological development with potential pathophysiological implications for clinically-relevant pregnancy and perinatal outcomes.
PubMed: 38878622
DOI: 10.1016/j.placenta.2024.05.138