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Biomedicines Jun 2024Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests... (Review)
Review
A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)-Associated Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: Possible Links to Pregestational Prediabetes.
Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests that maternal insults during pregnancy cause structural and functional changes in fetal organs, increasing the risk of chronic diseases like type 2 diabetes mellitus (T2DM) in adulthood. It is proposed that altered maternal physiology, such as increased glucocorticoid (GC) levels associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis in maternal stress and T2DM during pregnancy, exposes the fetus to excess GC. Prenatal glucocorticoid exposure reduces fetal growth and programs the fetal HPA axis, permanently altering its activity into adulthood. This programmed HPA axis is linked to increased risks of hypertension, cardiovascular diseases, and mental disorders in adulthood. With the global rise in T2DM, particularly among young adults of reproductive age, it is crucial to prevent its onset. T2DM is often preceded by a prediabetic state, a condition that does not show any symptoms, causing many to unknowingly progress to T2DM. Studying prediabetes is essential, as it is a reversible stage that may help prevent T2DM-related pregnancy complications. The existing literature focuses on HPA axis dysregulation in T2DM pregnancies and its link to fetal programming. However, the effects of prediabetes on HPA axis function, specifically glucocorticoid in pregnancy and fetal outcomes, are not well understood. This review consolidates research on T2DM during pregnancy, its impact on fetal programming via the HPA axis, and possible links with pregestational prediabetes.
PubMed: 38927579
DOI: 10.3390/biomedicines12061372 -
Biomedicines May 2024Amid the deepening imbalance in the supply and demand of allogeneic organs, xenotransplantation can be a practical alternative because it makes an unlimited supply of... (Review)
Review
Amid the deepening imbalance in the supply and demand of allogeneic organs, xenotransplantation can be a practical alternative because it makes an unlimited supply of organs possible. However, to perform xenotransplantation on patients, the source animals to be used must be free from infectious agents. This requires the breeding of animals using assisted reproductive techniques, such as somatic cell nuclear transfer, embryo transfer, and cesarean section, without colostrum derived in designated pathogen-free (DPF) facilities. Most infectious agents can be removed from animals produced via these methods, but several viruses known to pass through the placenta are not easy to remove, even with these methods. Therefore, in this narrative review, we examine the characteristics of several viruses that are important to consider in xenotransplantation due to their ability to cross the placenta, and investigate how these viruses can be detected. This review is intended to help maintain DPF facilities by preventing animals infected with the virus from entering DPF facilities and to help select pigs suitable for xenotransplantation.
PubMed: 38927388
DOI: 10.3390/biomedicines12061181 -
Biomedicines May 2024Inherited thrombophilia (IT) has been implicated as a potential causal factor of adverse pregnancy outcomes (APOs), including recurrent miscarriage with and without the...
Inherited thrombophilia (IT) has been implicated as a potential causal factor of adverse pregnancy outcomes (APOs), including recurrent miscarriage with and without the presence of antiphospholipid syndrome (APS). The aim of this study was to assess the prevalence and impact of IT on fetal-maternal outcomes and thrombotic risk in women within the spectrum of obstetric APS. Three hundred and twenty-eight women with APS-related obstetric morbidity ever pregnant were included. Of these, 74 met the APS classification criteria, 169 were non-criteria (NC)-APS, and 85 were seronegative (SN)-APS. Patients with other autoimmune diseases were excluded. APOs included early pregnancy loss, fetal death, preeclampsia, abruptio placentae, and preterm birth. Successful pregnancy was defined as the achievement of a live newborn. A literature search was also performed. The mean age of the overall group was 33.9 ± 5.3 years, and the patients were followed up for 35 (11-79) months. During the study period, there were 1332 pregnancies. Nearly 14% of the patients had an associated IT. IT patients more frequently received the standard-of-care (SoC) therapy. The presence of IT was not associated with worse maternal-fetal outcomes in patients treated with SoC treatment. Overall, IT patients had a lower frequency of newborns without treatment, especially those without definite APS. In addition, IT did not increase the risk of thrombosis during pregnancy or the postpartum period. A detailed analysis of the literature review identified only four publications related to our study and did not show conclusive evidence of the impact of IT on patients with obstetric APS. The group of women with APS-related obstetric morbidity and IT who did not receive treatment, especially those without definite APS, had a worse prognosis in terms of a live birth. However, with SoC therapy, the prognosis is similar in those patients without IT. The association of IT with APS does not seem to predispose to the development of thrombosis during pregnancy and/or the postpartum period.
PubMed: 38927381
DOI: 10.3390/biomedicines12061174 -
Biomolecules Jun 2024Preeclampsia, a hypertensive disease of pregnancy of unknown etiology, is intensely studied as a model of cardiovascular disease (CVD) not only due to multiple shared... (Review)
Review
Preeclampsia, a hypertensive disease of pregnancy of unknown etiology, is intensely studied as a model of cardiovascular disease (CVD) not only due to multiple shared pathologic elements but also because changes that develop over decades in CVD appear and resolve within days in preeclampsia. Those affected by preeclampsia and their offspring experience increased lifetime risks of CVD. At the systemic level, preeclampsia is characterized by increased cellular, membrane, and blood levels of cholesterol; however, cholesterol-dependent signaling, such as canonical Wnt/βcatenin, Hedgehog, and endothelial nitric oxide synthase, is downregulated indicating a cholesterol deficit with the upregulation of cholesterol synthesis and efflux. Hypoxia-related signaling in preeclampsia also appears to be paradoxical with increased Hypoxia-Inducible Factors in the placenta but measurably increased oxygen in maternal blood in placental villous spaces. This review addresses the molecular mechanisms by which excessive systemic cholesterol and deficient cholesterol-dependent signaling may arise from the effects of dietary lipid variance and environmental membrane modifiers causing the cellular hypoxia that characterizes preeclampsia.
Topics: Humans; Pre-Eclampsia; Pregnancy; Female; Cholesterol; Hypoxia; Placenta; Signal Transduction; Animals
PubMed: 38927094
DOI: 10.3390/biom14060691 -
BMC Pregnancy and Childbirth Jun 2024Preeclampsia (PE) is a pregnancy-related multi-organ disease and a significant cause of incidence rate and mortality of pregnant women and newborns worldwide. Delivery...
OBJECTIVE
Preeclampsia (PE) is a pregnancy-related multi-organ disease and a significant cause of incidence rate and mortality of pregnant women and newborns worldwide. Delivery remains the only available treatment for PE. This study aims to establish a dynamic prediction model for PE.
METHODS
A total of 737 patients who visited our hospital from January 2021 to June 2022 were identified according to the inclusion and exclusion criteria, forming the primary dataset. Additionally, 176 singleton pregnant women who visited our hospital from July 2022 to November 2022 comprised the verification set. We investigated different gestational weeks of sFlt-1/PLGF (soluble FMS-like tyrosine kinase-1, placental growth factor) ratio combined with maternal characteristics and routine prenatal laboratory results in order to predict PE in each trimester. Multivariate logistic regression was used to establish the prediction model for PE at different gestational weeks. The discrimination, calibration, and clinical validity were utilized to evaluate predictive models as well as models in external validation queues.
RESULTS
At 20-24 weeks, the obtained prediction model for PE yielded an area under the curve of 0.568 (95% confidence interval, 0.479-0.657). At 25-29 weeks, the obtained prediction model for PE yielded an area under the curve of 0.773 (95% confidence interval, 0.703-0.842)and 0.731 (95% confidence interval, 0.653-0.809) at 30-34 weeks. After adding maternal factors, uterine artery pulsation index(Ut-IP), and other laboratory indicators to the sFlt-1/PLGF ratio, the predicted performance of PE improved. It found that the AUC improved to 0.826(95% confidence interval, 0.748 ∼ 0.904) at 20-24 weeks, 0.879 (95% confidence interval, 0.823 ∼ 0.935) at 25-29 weeks, and 0.862(95% confidence interval, 0.799 ∼ 0.925) at 30-34 weeks.The calibration plot of the prediction model indicates good predictive accuracy between the predicted probability of PE and the observed probability. Furthermore, decision-curve analysis showed an excellent clinical application value of the models.
CONCLUSION
Using the sFlt-1/PLGF ratio combined with multiple factors at 25-29 weeks can effectively predict PE, but the significance of re-examination in late pregnancy is not significant.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; Vascular Endothelial Growth Factor Receptor-1; Placenta Growth Factor; Adult; Biomarkers; Predictive Value of Tests; Gestational Age; Logistic Models; Retrospective Studies
PubMed: 38926668
DOI: 10.1186/s12884-024-06627-4 -
The Journal of Maternal-fetal &... Dec 2024Preeclampsia is associated with adverse perinatal outcomes, including fetal growth restriction (FGR) and preterm delivery. The maternal serum ratio of soluble fms-like... (Observational Study)
Observational Study
INTRODUCTION
Preeclampsia is associated with adverse perinatal outcomes, including fetal growth restriction (FGR) and preterm delivery. The maternal serum ratio of soluble fms-like tyrosine kinase receptor-1 (sFlt-1) to placental growth factor (PlGF) can be used to evaluate placental dysfunction in cases of preeclampsia and FGR. A need for delivery within 2 days has been recommended for sFlt-1/PlGF ratios > 655 (normal ratio < 38) measured before 34 weeks' gestation. However, few studies have assessed this recommendation in a real-world setting and there remains a need for further evidence-based guidance on the use of the ratio in delivery timing planning in this situation.
AIM
To assess the need for delivery within 2 days associated with sFlt-1/PlGF ratios > 655 before 34 weeks' gestation.
METHODS
A retrospective audit of all sFlt-1/PlGF ratio test results obtained at a single maternity hospital between September 2016 and November 2022. The primary outcome was time to delivery after recording a ratio > 655 in patients with a pregnancy between 20 + 0 and 33 + 6 weeks' gestation. Statistical analysis was performed using IBM SPSS Statistics v29.0.0.0.
RESULTS
During the study period a total of 33 patients with suspected or confirmed preeclampsia and/or FGR recorded sFlt-1/PlGF ratios > 655 before 34 + 0 weeks' gestation. Amongst cases with ratios > 655, median time to delivery was 4 days (IQR 1.0-9.0), with 14 (42.4%) delivering in ≤ 2 days, 8 (24.2%) delivering between 2 and 7 days and 11 (33.3%) delivering after 7 days. A significant inverse correlation was observed between time to delivery and gestational age at the time of ratio testing ( = -0.484, = 0.004).
DISCUSSION
This study provides updated recommendations on the use of the sFlt-1/PlGF ratio in predicting the risk of imminent delivery amongst those with high ratios > 655 measured before 34 weeks' gestation. Our results suggest that the risk of imminent delivery can be stratified based on ratio level and gestational age, which in combination with the results of other clinical assessments, can be used to plan delivery timing and allow for considerations of fetal lung maturing corticosteroid and neuroprotective magnesium sulfate therapies prior to delivery.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Vascular Endothelial Growth Factor Receptor-1; Placenta Growth Factor; Adult; Premature Birth; Pre-Eclampsia; Gestational Age; Biomarkers; Fetal Growth Retardation; Infant, Newborn
PubMed: 38926094
DOI: 10.1080/14767058.2024.2371047 -
Tierarztliche Praxis. Ausgabe G,... Jun 2024In horses, parturition is characterized by the fact that any delays may rapidly result in the death of the foal. Therefore, birth monitoring and the rapid detection of... (Review)
Review
In horses, parturition is characterized by the fact that any delays may rapidly result in the death of the foal. Therefore, birth monitoring and the rapid detection of dystocia are of great importance. For this purpose, the differentiation between behavior associated with physiological parturition and activities related to difficult parturition is important. The aim of this publication is to present the physiological behavior of mares during parturition on the basis of a literature review. The behavior of mares in the opening phase of parturition is highly individual. In general, it is characterized by an increase in movement activity. In this phase of parturition, 13 different behaviors have been described (e. g. lying down and standing up, cessation of feed intake, local sweating, frequent defecation and urination). Mares show a more uniform pattern of behavior in the expulsion phase and the following phase of expulsion of the fetal membranes and placenta. More than 95% of mares give birth in the lateral position. A mare usually remains in recumbency for several minutes following the expulsion of the fetus. Immediately after standing up, the mare begins to intensely interact with the foal. The expulsion of the fetal membranes and the placenta usually takes place in a standing position. From a clinical point of view, it is important to give consideration to the difficulty in recognizing the opening phase of parturition due to the mares' individual behavior patterns.
Topics: Horses; Female; Animals; Parturition; Pregnancy; Behavior, Animal
PubMed: 38925128
DOI: 10.1055/a-2321-4422 -
Biology of Reproduction Jun 2024Preeclampsia (PE) is a complication of pregnancy characterized by the new onset of hypertension after 20 weeks of gestation. The incidence of PE is steadily rising,...
Preeclampsia (PE) is a complication of pregnancy characterized by the new onset of hypertension after 20 weeks of gestation. The incidence of PE is steadily rising, posing a significant threat to the lives of both the pregnant woman and the fetus. Most studies on PE pathogenesis currently focus on the placenta, but maternal decidualization forms the foundation for placental growth and development. Recent studies have shown that impaired decidualization is also a cause of PE. Decidualization is a process where endometrial stromal cells gradually transform into secretory decidual cells during early pregnancy. While NSUN5 encodes a member of a conserved family of proteins, its role in pregnancy remains unknown. In this study, we conducted experiments and observed a significant downregulation of NSUN5 expression in severe preeclampsia decidual tissues compared to those of normal pregnant women. When inducing decidualization in vitro, we found an increase in NSUN5 expression. However, when we used siRNA to knockdown NSUN5 expression, the process of decidualization was prevented. Moreover, we observed a decrease in ATP content during both cell decidualization and after knockdown of NSUN5. Finally, through immunoprecipitation combined with mass spectrometry, we discovered that the protein ATP5B interacts with NSUN5. Furthermore, after knocking down ATP5B using siRNA, we observed impaired decidualization. Moreover, transfection with siRNA to suppress NSUN5 resulted in a decrease in ATP5B expression. These significant findings provide strong evidence that NSUN5 plays a crucial role in decidualization and is closely associated with the development of PE through its interaction with ATP5B.
PubMed: 38924712
DOI: 10.1093/biolre/ioae096 -
Placental apoptosis increased by hypoxia inducible Factor-1 stabilization is counteracted by leptin.Biology of Reproduction Jun 2024During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed towards the relevance of...
During pregnancy, apoptosis is a physiological event critical in the remodeling and aging of the placenta. Increasing evidence has pointed towards the relevance of hypoxia as modulator of trophoblast cell death. Previous reports have shown that leptin, a placental cytokine, promotes cell survival in both cell culture and placental explant models. The aim of this work is to establish the role of leptin in apoptosis under hypoxic condition in trophoblast cells. In this study, we evaluated the effect of cobalt chloride, a hypoxia mimicking agent that stabilizes the expression of hypoxia inducible factor-1 alpha (HIF-1α), on Swan-71 and human placental explants. Hypoxia chamber was also used to generate 2% oxygen. Apoptosis was determined by the presence of apoptotic nucleus, fragmentation of DNA and Caspase-3 and PARP-1 cleavage. The pro-apoptotic proteins BAX, BID, BAD and BAK and the anti-apoptotic effectors BCL-2, BCL-xL and MCL-1 were also analyzed. We found that HIF-1α stabilization increased the appearance of apoptotic nucleus, fragmentation of DNA, and Caspase-3 and PARP-1 cleavage. Hypoxia mimicking conditions enhanced the expression of pro-apoptotic effectors BAX, BID, BAD and BAK. HIF-1α stabilization also downregulated the level of BCL-2, BCL-xL and MCL-1. All these apoptotic parameters changes were reversed with leptin treatment. Moreover, we showed that leptin action on apoptosis modulation involves PI3K and MAPK signaling pathways. Obtained data demonstrate that HIF-1α stabilization induces apoptosis in human placenta and leptin counteracts this effect, reinforcing its role as a survival cytokine.
PubMed: 38924703
DOI: 10.1093/biolre/ioae095 -
Advanced Science (Weinheim,... Jun 2024The placenta links feto-maternal circulation for exchanges of nutrients, gases, and metabolic wastes between the fetus and mother, being essential for pregnancy process...
The placenta links feto-maternal circulation for exchanges of nutrients, gases, and metabolic wastes between the fetus and mother, being essential for pregnancy process and maintenance. The allantois and mesodermal components of amnion, chorion, and yolk sac are derived from extraembryonic mesoderm (Ex-Mes), however, the mechanisms contributing to distinct components of the placenta and regulation the interactions between allantois and epithelium during chorioallantoic fusion and labyrinth formation remains unclear. Isl1 is expressed in progenitors of the Ex-Mes and allantois the Isl1 mut mouse line is analyzed to investigate contribution of Isl1 Ex-Mes / allantoic progenitors to cells of the allantois and placenta. This study shows that Isl1 identifies the Ex-Mes progenitors for endothelial and vascular smooth muscle cells, and most of the mesenchymal cells of the placenta and umbilical cord. Deletion of Isl1 causes defects in allantois growth, chorioallantoic fusion, and placenta vessel morphogenesis. RNA-seq and CUT&Tag analyses revealed that Isl1 promotes allantoic endothelial, inhibits mesenchymal cell differentiation, and allantoic signals regulated by Isl1 mediating the inductive interactions between the allantois and chorion critical for chorionic epithelium differentiation, villous formation, and labyrinth angiogenesis. This study above reveals that Isl1 plays roles in regulating multiple genetic and epigenetic pathways of vascular morphogenesis, provides the insight into the mechanisms for placental formation, highlighting the necessity of Isl1 for placenta formation/pregnant maintenance.
PubMed: 38923264
DOI: 10.1002/advs.202400238