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BioRxiv : the Preprint Server For... Jun 2024Studying the human placenta through in vitro cell culture methods is necessary due to limited access and amenability of human placental tissue to certain experimental...
Studying the human placenta through in vitro cell culture methods is necessary due to limited access and amenability of human placental tissue to certain experimental methods as well as distinct anatomical and physiological differences between animal and human placentas. Selecting an in vitro culture model of the human placenta is challenging due to representation of different trophoblast cell types with distinct biological roles and limited comparative studies that define key characteristics of these models. Therefore, the aim of this research was to create a comprehensive transcriptomic comparison of common in vitro models of the human placenta compared to bulk placental tissue from the CANDLE and GAPPS cohorts (N=1083). We performed differential gene expression analysis on publicly available RNA sequencing data from 6 common in vitro models of the human placenta (HTR-8/SVneo, BeWo, JEG-3, JAR, Primary Trophoblasts, and Villous Explants) and compared to CANDLE and GAPPS bulk placental tissue or cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast cell types derived from bulk placental tissue. All in vitro placental models had a substantial number of differentially expressed genes (DEGs, FDR<0.01) compared to the CANDLE and GAPPS placentas (Average DEGs=10,873), and the individual trophoblast cell types (Average DEGs=5,346), indicating that there are vast differences in gene expression compared to bulk and cell-type specific human placental tissue. Hierarchical clustering identified 53 gene clusters with distinct expression profiles across placental models, with 22 clusters enriched for specific KEGG pathways, 7 clusters enriched for high-expression placental genes, and 7 clusters enriched for absorption, distribution, metabolism, and excretion genes. In vitro placental models were classified by fetal sex based on expression of Y-chromosome genes that identified HTR-8/SVneo cells as being of female origin, while JEG-3, JAR, and BeWo cells are of male origin. Overall, none of the models were a close approximation of the transcriptome of bulk human placental tissue, highlighting the challenges with model selection. To enable researchers to select appropriate models, we have compiled data on differential gene expression, clustering, and fetal sex into an accessible web application: "Comparative Transcriptomic Placental Model Atlas (CTPMA)" which can be utilized by researchers to make informed decisions about their selection of in vitro placental models.
PubMed: 38915703
DOI: 10.1101/2024.06.14.598695 -
BioRxiv : the Preprint Server For... Jun 2024PARP1 (ARTD1) and Tankyrases (TNKS1/TNKS2; PARP5a/5b) are poly-ADP-ribose polymerases (PARPs) with catalytic and non-catalytic functions that regulate both the genome...
PARP1 (ARTD1) and Tankyrases (TNKS1/TNKS2; PARP5a/5b) are poly-ADP-ribose polymerases (PARPs) with catalytic and non-catalytic functions that regulate both the genome and proteome during zygotic genome activation (ZGA), totipotent, and pluripotent embryonic stages. Here, we show that primed, conventional human pluripotent stem cells (hPSC) cultured continuously under non-specific TNKS1/TNKS2/PARP1-inhibited chemical naive reversion conditions underwent epigenetic reprogramming to clonal blastomere-like stem cells. TIRN stem cells concurrently expressed hundreds of gene targets of the ZGA-priming pioneer factor DUX4, as well as a panoply of four-cell (4C)-specific (e.g., TPRXL, HOX clusters), eight-cell (8C)-specific (e.g., DUXA, GSC, GATA6), primitive endoderm-specific (e.g., GATA4, SOX17), trophectoderm-specific (e.g., CDX2, TFAP2C), and naive epiblast-specific (e.g., DNMT3L, NANOG, POU5F1(OCT4)) factors; all in a hybrid, combinatorial single-cell manner. Mapping of proteomic and single-cell expressions of TIRN cells against human preimplantation embryo references identified them as relatively homogenous 4C-8C stage populations. Injection of TIRN cells into murine 8C-16C-staged embryos resulted in efficient totipotent-like single cell contributions of human cells to both extra-embryonic (trophectoderm, placenta) and embryonic (neural, fetal liver, hematopoietic) lineages in human-murine blastocyst and fetal chimeras. Pairing of proteome with ubiquitinome analyses of TIRN cells revealed a global shutdown of ADP-ribosylation, and a perturbed TNKS/PARP1 equilibrium which not only impacted the protein levels of hundreds of TNKS/PARP1 substrates via a rewiring of the ubiquitin-proteosome system (UPS), but also de-repressed expression of hundreds of developmental genes associated with PARP1 suppression. ChIP-Seq analysis of core NANOG-SOX2-OCT4 (NSO) pluripotency factors in TIRN cells identified reprogrammed DUX4-accessible distal and cis-regulatory enhancer regions that were co-bound by PARP1 (NSOP). These NSOP enhancer regions possessed co-binding motifs for hundreds of the same ZGA-associated, embryonic, and extraembryonic lineage-specifying pioneer factors (e.g., HOX, FOX, GATA, SOX, TBX, CDX families) that were concurrently co-expressed in TIRN cells; suggesting that PARP1 and DUX4 cooperate with NSO pluripotency core factors to regulate the epigenetic plasticity of a human totipotency program. These findings provide the first demonstration that global, proteome-wide perturbations of post-translational modifications (i.e., ADP-ribosylation, ubiquitination) can regulate epigenetic reprogramming during human embryogenesis. Totipotent TIRN stem cells will provide a valuable cell culture model for studying the proteogenomic regulation of lineage specification from human blastomere stages and may facilitate the efficient generation of human organs in interspecies chimeras.
PubMed: 38915486
DOI: 10.1101/2024.06.14.598510 -
Frontiers in Public Health 2024Microplastics (MPs) are particles with a diameter of <5 mm. The disposal of plastic waste into the environment poses a significant and pressing issue concern globally.... (Review)
Review
Microplastics (MPs) are particles with a diameter of <5 mm. The disposal of plastic waste into the environment poses a significant and pressing issue concern globally. Growing worry has been expressed in recent years over the impact of MPs on both human health and the entire natural ecosystem. MPs impact the feeding and digestive capabilities of marine organisms, as well as hinder the development of plant roots and leaves. Numerous studies have shown that the majority of individuals consume substantial quantities of MPs either through their dietary intake or by inhaling them. MPs have been identified in various human biological samples, such as lungs, stool, placenta, sputum, breast milk, liver, and blood. MPs can cause various illnesses in humans, depending on how they enter the body. Healthy and sustainable ecosystems depend on the proper functioning of microbiota, however, MPs disrupt the balance of microbiota. Also, due to their high surface area compared to their volume and chemical characteristics, MPs act as pollutant absorbers in different environments. Multiple policies and initiatives exist at both the domestic and global levels to mitigate pollution caused by MPs. Various techniques are currently employed to remove MPs, such as biodegradation, filtration systems, incineration, landfill disposal, and recycling, among others. In this review, we will discuss the sources and types of MPs, the presence of MPs in different environments and food, the impact of MPs on human health and microbiota, mechanisms of pollutant adsorption on MPs, and the methods of removing MPs with algae and microbes.
Topics: Humans; Microplastics; Ecosystem; Water Pollutants, Chemical; Environmental Monitoring
PubMed: 38912266
DOI: 10.3389/fpubh.2024.1411389 -
Medical Image Computing and... Oct 2023The placenta is a valuable organ that can aid in understanding adverse events during pregnancy and predicting issues post-birth. Manual pathological examination and...
The placenta is a valuable organ that can aid in understanding adverse events during pregnancy and predicting issues post-birth. Manual pathological examination and report generation, however, are laborious and resource-intensive. Limitations in diagnostic accuracy and model efficiency have impeded previous attempts to automate placenta analysis. This study presents a novel framework for the automatic analysis of placenta images that aims to improve accuracy and efficiency. Building on previous vision-language contrastive learning (VLC) methods, we propose two enhancements, namely Pathology Report Feature Recomposition and Distributional Feature Recomposition, which increase representation robustness and mitigate feature suppression. In addition, we employ efficient neural networks as image encoders to achieve model compression and inference acceleration. Experiments validate that the proposed approach outperforms prior work in both performance and efficiency by significant margins. The benefits of our method, including enhanced efficacy and deployability, may have significant implications for reproductive healthcare, particularly in rural areas or low- and middle-income countries.
PubMed: 38911098
DOI: 10.1007/978-3-031-43987-2_12 -
Case Reports in Women's Health Jun 2024Caesarean scar pregnancy (CSP) occurs when the gestational sac implants in the region of a scar from a previous caesarean delivery. CSP can lead to life-threatening...
Caesarean scar pregnancy (CSP) occurs when the gestational sac implants in the region of a scar from a previous caesarean delivery. CSP can lead to life-threatening complications, including severe haemorrhage, uterine rupture, placenta accreta spectrum (PAS) and hysterectomy. A 40-year-old woman with one previous caesarean was referred to the specialist centre at 17 weeks of gestation with concerns about CSP. At 19 weeks, she was admitted with abdominal pain. Due to raised body habitus, accurate ultrasound assessment was challenging, necessitating reliance on magnetic resonance imaging (MRI). The patient desired to continue the pregnancy, but due to pain and concerns about uterine rupture she consented to a laparotomy to potentially terminate the pregnancy. Findings during the laparotomy were reassuring, leading to the decision not to terminate the pregnancy. The patient remained hospitalised until delivery by caesarean-hysterectomy at 33 weeks. Histopathology confirmed the PAS diagnosis. This case highlights the importance of achieving early diagnosis and obtaining clear sonographic findings. It emphasises the pitfalls of relying on MRI due to its tendency to over-diagnose severity. It emphasises the urgency for improved training in this domain. Early sonographic diagnosis allows safer performance of termination of pregnancy. It also provides women who continue with the pregnancy useful prognostic signs to facilitate decisions on the optimal gestation for delivery. Determining optimal conservative management for CSP remains an ongoing challenge. This case emphasises the importance of multidisciplinary discussion, comprehensive patient counselling and involving patients in their care planning, to create an individualised and adaptable treatment plan.
PubMed: 38911044
DOI: 10.1016/j.crwh.2024.e00626 -
Endocrine Journal Jun 2024Although growth hormone (GH) and prolactin (PRL) are usually recognized as pituitary hormones, their expression is not restricted to the adenohypophysis and can also be...
Although growth hormone (GH) and prolactin (PRL) are usually recognized as pituitary hormones, their expression is not restricted to the adenohypophysis and can also be found in extra-pituitary tissues including placenta. Furthermore, GH, PRL, and their receptors structurally belong to the cytokine family of proteins, and indeed they have remarkable pleiotropic effects. In this review, we analyzed the biological roles of GH/PRL from an evolutionary perspective. We have recognized that the biological significance of GH/PRL can be summarized as follows: cytokines (metabokines) that regulate the shift of nutrients and even of whole bodies to live in the most appropriate environment(s) for conducting growth and reproduction. In this sense, the common keyword of the two metabokines is "shift" for environmental adaptation. Considering that these metabokines flexibly changed their biological roles, GH/PRL may have played important roles during vertebrate evolution.
PubMed: 38910132
DOI: 10.1507/endocrj.EJ24-0118 -
Placenta Jun 2024Fetal growth restriction (FGR) is a clinically important human pregnancy disorder that is thought to originate early in pregnancy and while its aetiology is not well...
Fetal growth restriction (FGR) is a clinically important human pregnancy disorder that is thought to originate early in pregnancy and while its aetiology is not well understood, the disorder is associated with placental insufficiency. Currently treatment for FGR is limited by increased surveillance using ultrasound monitoring and premature delivery, or corticosteroid medication in the third trimester to prolong pregnancy. There is a pressing need for novel strategies to detect and treat FGR at its early stage. Homeobox genes are well established as master regulators of early embryonic development and increasing evidence suggests they are also important in regulating early placental development. Most important is that specific homeobox genes are abnormally expressed in human FGR. This review focusses on identifying the molecular pathways controlled by homeobox genes in the normal and FGR-affected placenta. This information will begin to address the knowledge gap in the molecular aetiology of FGR and lay the foundation for identifying potential diagnostic and therapeutic targets.
PubMed: 38908943
DOI: 10.1016/j.placenta.2024.06.010 -
BMJ Open Jun 2024To identify determinants of puerperal sepsis among postpartum women attending East Shoa Zone public hospitals, Central Ethiopia, 2023.
OBJECTIVE
To identify determinants of puerperal sepsis among postpartum women attending East Shoa Zone public hospitals, Central Ethiopia, 2023.
DESIGN AND SETTING
An institutional-based, unmatched case-control study was conducted from 19 June 2023 to 4 September 2023, in East Shoa Zone public hospitals.
PARTICIPANTS
495 postpartum women (100 cases and 395 controls) were selected using systematic sampling techniques. Data were collected through face-to-face interviews and from medical charts using a pretested, structured questionnaire. The AOR with its corresponding 95% CI was used to identify determinant variables. Findings were presented in texts and tables.
OUTCOME MEASURES
The medical charts of participants were reviewed to identify those who had developed puerperal sepsis.
RESULTS
Anaemia (AOR 6.05; 95% CI 2.57 to 14.26), undernourishment (AOR 4.43; 95% CI 1.96 to 10.01), gestational diabetes mellitus (AOR 3.26; 95% CI 1.22 to 8.74), postpartum haemorrhage (AOR 3.17; 95% CI 1.28 to 7.87), obstructed labour (AOR 2.76; 95% CI 1.17 to 6.52), multiparity (AOR 2.54; 95% CI 1.17 to 5.50), placenta previa (AOR 2.27; 95% CI 1.11 to 4.67) and vaginal examination ≥5 times (AOR 2.19; 95% CI 1.05 to 4.54) were the independent determinants of puerperal sepsis in this study.
CONCLUSION
This study found that gestational diabetes mellitus, anaemia, undernourishment, placenta previa, obstructed labour, postpartum haemorrhage and five or more per-vaginal examinations during labour were the determinants of puerperal sepsis. Therefore, it is recommended that obstetric care providers strictly adhere to guidelines on the number of vaginal exams that should be performed throughout labour and that they perform these exams using the appropriate infection-prevention techniques. In addition, they should provide comprehensive health education on nutrition during pregnancy and postnatal periods and the importance of iron supplements.
Topics: Humans; Female; Ethiopia; Case-Control Studies; Adult; Hospitals, Public; Sepsis; Pregnancy; Puerperal Infection; Risk Factors; Young Adult; Postpartum Period; Postpartum Hemorrhage; Anemia; Adolescent; Diabetes, Gestational
PubMed: 38908838
DOI: 10.1136/bmjopen-2023-083230 -
American Journal of Obstetrics and... Jun 2024It is estimated that over 2 million cases of fetal death occur worldwide every year, but, despite the high incidence, several basic and clinical characteristics of this...
BACKGROUND
It is estimated that over 2 million cases of fetal death occur worldwide every year, but, despite the high incidence, several basic and clinical characteristics of this disorder are still unclear. Placenta is suggested to play a central role in fetal death. Placenta produces hormones, cytokines and growth factors that modulate functions of the placental-maternal unit. Fetal death has been correlated with impaired secretion of some of these regulatory factors.
OBJECTIVE(S)
The aim of the present study was to evaluate, in placentas collected from fetal death, the gene expression of inflammatory, proliferative and protective factors.
STUDY DESIGN
Cases of fetal death in singleton pregnancy were retrospectively selected, excluding pregnancies complicated by fetal anomalies, gestational diabetes, intrauterine growth restriction and moderate to severe maternal diseases. A group of placentas collected from healthy singleton term pregnancies were used as controls. Groups were compared regarding maternal and gestational age, fetal sex and birth weight. Placental mRNA expression of inflammatory (IL-6), proliferative (Activin A, TGF-β1) and regulatory (VEGF, VEGFR2, ATP-binding cassette (ABC) transporters ABCB1 and ABCG2, sphingosine 1-phosphate (S1P) signaling pathway) markers was conducted using real-time PCR. Statistical analysis and graphical representation of the data were performed using the GraphPad Prism 5 software. For the statistical analysis, Student's t-test was used, and P values < 0.05 were considered significant.
RESULTS
Placental mRNA expression of IL-6 and VEGFR2 resulted significantly higher in the fetal death group compared to controls (P<0.01), while activin A, ABCB1 and ABCG2 expression resulted significantly lower (P<0.01). A significant alteration in the S1P signaling pathway was found in the fetal death group, with an increased expression of the specific receptor isoforms sphingosine 1-phosphate receptor 1, 3 and 4 (S1P, S1P, S1P) and of sphingosine kinase 2 (SK2), one of the enzyme isoforms responsible for S1P synthesis (P<0.01).
CONCLUSION
(s): The present study confirmed a significantly increased expression of placental IL-6 and VEGFR2 mRNA, and for the first time showed an increased expression of S1P receptors and SK2 as well as a decreased expression of activin A and of selected ATP-binding cassette transporters, suggesting that multiple inflammatory and protective factors are deranged in placenta of fetal death.
PubMed: 38908653
DOI: 10.1016/j.ajog.2024.06.011 -
American Journal of Obstetrics and... Jun 2024To investigate the association between actual and planned modes of delivery, neonatal mortality, and short-term outcomes among preterm pregnancies ≤32 weeks of gestation. (Review)
Review
Cesarean delivery is associated with lower neonatal mortality among breech pregnancies - a systematic review and meta-analysis of preterm deliveries ≤32 weeks of gestation.
OBJECTIVE
To investigate the association between actual and planned modes of delivery, neonatal mortality, and short-term outcomes among preterm pregnancies ≤32 weeks of gestation.
DATA SOURCES
A systematic literature search was conducted in three main databases (PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 16, 2022. The protocol was registered in advance in the International Prospective Register of Systematic Reviews (CRD42022377870).
STUDY ELIGIBILITY CRITERIA
Eligible studies examined pregnancies ≤ 32nd gestational week. All infants received active care, and the outcomes were reported separately by different modes of delivery. Singleton and twin pregnancies at vertex and breech presentations were included. Studies that included pregnancies complicated with preeclampsia and abruptio placentae were excluded. Primary outcomes were neonatal mortality and intraventricular hemorrhage.
STUDY APPRAISAL AND SYNTHESIS METHODS
Articles were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random effects model-based odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. ROBINS-I was used to assess the risk of bias.
RESULTS
A total of nineteen observational studies were included involving a total of 16,042 preterm infants in this systematic review and meta-analysis. Actual cesarean delivery improves survival (odds ratio, 0.62; 95% confidence interval, 0.42 to 0.9) and decreases the incidence of intraventricular hemorrhage (odds ratio, 0.70; confidence interval, 0.57 to 0.85) compared to vaginal delivery. Planned cesarean delivery does not improve the survival of very and extremely preterm infants compared to vaginal delivery (odds ratio, 0.87; 95% confidence interval, 0.53 to 1.44). Subset analysis found significantly lower odds of death for singleton breech preterm deliveries born by both planned (odds ratio, 0.56; 95% confidence interval, 0.32 to 0.98) and actual (odds ratio, 0.34; 95% confidence interval, 0.13 to 0.88) cesarean delivery.
CONCLUSION
Cesarean delivery should be the mode of delivery for preterm ≤32 weeks of gestation breech births due to the higher mortality in preterm infants born via vaginal delivery.
PubMed: 38908650
DOI: 10.1016/j.ajog.2024.06.015