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Archives of Disease in Childhood. Fetal... Jun 2024The placenta contains valuable clinical information that is linked to fetal development, neonatal morbidity and mortality, and future health outcomes. Both gross... (Review)
Review
The placenta contains valuable clinical information that is linked to fetal development, neonatal morbidity and mortality, and future health outcomes. Both gross inspection and histopathological examination of the placenta may identify intrinsic or secondary placental lesions, which can contribute directly to adverse neonatal outcomes or indicate the presence of an unfavourable intrauterine environment. Placental examination therefore forms an essential component of the care of high-risk neonates and at perinatal post-mortem examination. In this article, we describe the clinical value of placental examination for paediatricians and perinatal clinicians. We discuss common pathological findings on general inspection of the placenta with photographic examples and provide an overview of the placental pathological examination, including how to interpret key findings. We also address the medico-legal and financial implications of placental examinations and describe current and future clinical considerations for clinicians in regard to placental examination.
Topics: Humans; Pregnancy; Female; Placenta; Infant, Newborn; Placenta Diseases
PubMed: 37751993
DOI: 10.1136/archdischild-2023-325674 -
Cell Communication and Signaling : CCS Dec 2023Yes-associated protein (YAP) is a pivotal regulator in cellular proliferation, survival, differentiation, and migration, with significant roles in embryonic development,... (Review)
Review
Yes-associated protein (YAP) is a pivotal regulator in cellular proliferation, survival, differentiation, and migration, with significant roles in embryonic development, tissue repair, and tumorigenesis. At the maternal-fetal interface, emerging evidence underscores the importance of precisely regulated YAP activity in ensuring successful pregnancy initiation and progression. However, despite the established association between YAP dysregulation and adverse pregnancy outcomes, insights into the impact of aberrant YAP levels in fetal-derived, particularly trophoblast cells, and the ensuing dysfunction at the maternal-fetal interface remain limited. This review comprehensively examines YAP expression and its regulatory mechanisms in trophoblast cells throughout pregnancy. We emphasize its integral role in placental development and maternal-fetal interactions and delve into the correlations between YAP dysregulation and pregnancy complications. A nuanced understanding of YAP's functions during pregnancy could illuminate intricate molecular mechanisms and pave the way for innovative prevention and treatment strategies for pregnancy complications. Video Abstract.
Topics: Pregnancy; Female; Humans; Placenta; Trophoblasts; Transcription Factors; Adaptor Proteins, Signal Transducing; Pregnancy Complications
PubMed: 38098027
DOI: 10.1186/s12964-023-01371-2 -
Life Sciences Apr 2024Ferroptosis, a novel mode of cell death characterized by lipid peroxidation and oxidative stress, plays an important role in the pathogenesis of preeclampsia (PE). The...
AIMS
Ferroptosis, a novel mode of cell death characterized by lipid peroxidation and oxidative stress, plays an important role in the pathogenesis of preeclampsia (PE). The aim of this study is to determine the role of Nox2 in the ferroptosis of trophoblast cells, along with the underlying mechanisms.
METHODS
The mRNA and protein levels of Nox2, STAT3, and GPX4 in placental tissues and trophoblast cells were respectively detected by qRT-PCR and western blot analysis. CCK8, transwell invasion and tube formation assays were used to evaluate the function of trophoblast cells. Ferroptosis was evaluated using flow cytometry and the lipid peroxidation assay. Glycolysis and mitochondrial respiration were investigated by detecting the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) using Seahorse extracellular flux technology. The t-test or one-way ANOVA was used for statistical analysis.
KEY FINDINGS
Nox2 was up-regulated while STAT3 and GPX4 were down-regulated in PE placental tissues. Nox2 knockdown inhibited ferroptosis in trophoblast cells, which was shown by enhanced proliferation and invasion, decreased ROS and lipid peroxide levels, and reduced glycolysis and mitochondrial dysfunction. Nox2 negatively correlated with MVD in PE placentas, and Nox2 knockdown restored ferroptosis-inhibited tube formation. Nox2 could interact with STAT3. Inhibiting Nox2 restored ferroptosis-induced alterations in the mRNA and protein levels of STAT3 and GPX4.
SIGNIFICANCE
Nox2 may trigger ferroptosis through the STAT3/GPX4 pathway, subsequently leading to regulation of mitochondrial respiration, transition of glycolysis, and inhibition of placental angiogenesis. Therefore, targeted inhibition of Nox2 is expected to become a new therapeutic target for PE.
Topics: Female; Humans; Pregnancy; Cell Line; Ferroptosis; Placenta; Pre-Eclampsia; RNA, Messenger; STAT3 Transcription Factor; Trophoblasts
PubMed: 38460811
DOI: 10.1016/j.lfs.2024.122555 -
Biology of Reproduction Aug 2023The present study aimed to investigate the regulation of placentas and uterus remodeling and involvement of estradiol in gestational diabetes mellitus. To achieve this,...
The present study aimed to investigate the regulation of placentas and uterus remodeling and involvement of estradiol in gestational diabetes mellitus. To achieve this, we established in vitro and in vivo models for gestational diabetes mellitus placentas by culturing human placental choriocarcinoma cells (BeWo) under hyperglycemic concentration and treating pregnant rats with streptozotocin. We evaluated the expression of angiogenesis-related proteins. The expression of the anti-angiogenic factor, excess placental soluble fms-like tyrosine kinase 1 was increased in our in vitro gestational diabetes mellitus model compared with the control. Moreover, the expressions of placental soluble fms-like tyrosine kinase 1 and the von Willebrand factor were also significantly elevated in the placenta of streptozotocin-treated rats. These data indicate the disruption of angiogenesis in the gestational diabetes mellitus placentas. The expression levels of connexin 43, a component of the gap junction and collagen type I alpha 2 chain, a component of the extracellular matrix, were decreased in the gestational diabetes mellitus uterus. These results suggest that uterus decidualization and placental angiogenesis are inhibited in gestational diabetes mellitus rats. Our results also showed upregulation of the expression of genes regulating estradiol synthesis as well as estrogen receptors in vivo models. Accordingly, the concentration of estradiol measured in the culture medium under hyperglycemic conditions, as well as in the serum and placenta of the streptozotocin-treated rats, was significantly elevated compared with the control groups. These results suggest that the dysregulated remodeling of the placenta and uterus may result in the elevation of estradiol and its signaling pathway in the gestational diabetes mellitus animal model to maintain pregnancy.
Topics: Pregnancy; Female; Rats; Animals; Humans; Placenta; Diabetes, Gestational; Vascular Endothelial Growth Factor Receptor-1; Streptozocin; Uterus; Estradiol; Vascular Endothelial Growth Factor A
PubMed: 37255320
DOI: 10.1093/biolre/ioad059 -
Fetal and Pediatric Pathology 2024The placenta, the foremost and multifaceted organ in fetal and maternal biology, is pivotal in facilitating optimal intrauterine fetal development. Remarkably, despite... (Review)
Review
The placenta, the foremost and multifaceted organ in fetal and maternal biology, is pivotal in facilitating optimal intrauterine fetal development. Remarkably, despite its paramount significance, the placenta remains enigmatic, meriting greater comprehension given its central influence on the health trajectories of both the fetus and the mother. Preeclampsia (PE) and intrauterine fetal growth restriction (IUGR), prevailing disorders of pregnancy, stem from compromised placental development. PE, characterized by heightened mortality and morbidity risks, afflicts 5-7% of global pregnancies, its etiology shrouded in ambiguity. Pertinent pathogenic hallmarks of PE encompass inadequate restructuring of uteroplacental spiral arteries, placental ischemia, and elevated levels of vascular endothelial growth factor receptor-1 (VEGFR-1), also recognized as soluble FMS-like tyrosine kinase-1 (sFlt-1). During gestation, the placental derivation of sFlt-1 accentuates its role as an inhibitory receptor binding to VEGF-A and placental growth factor (PlGF), curtailing target cell accessibility. This review expounds upon the placenta's defining cellular component of the trophoblast, elucidates the intricacies of PE pathogenesis, underscores the pivotal contribution of sFlt-1 to maternal pathology and fetal safeguarding, and surveys recent therapeutic strides witnessed in the past decade.
Topics: Pregnancy; Humans; Female; Placenta; Pre-Eclampsia; Placenta Growth Factor; Vascular Endothelial Growth Factor A; Placentation; Fetal Growth Retardation
PubMed: 37906285
DOI: 10.1080/15513815.2023.2274823 -
Tissue & Cell Jun 2024GATA3 plays critical roles in the development and function of various tissues and organs throughout the body. Likewise, TGF-β signaling is critical for placental...
GATA3 plays critical roles in the development and function of various tissues and organs throughout the body. Likewise, TGF-β signaling is critical for placental development and can interact with GATA3. We aimed to investigate the involvement of the multifunctional cytokine and transcription factor in trophoblast development. By using immunohistochemistry, we evaluated the localization and expression level of GATA3 and TGF-β in placentas at term of normal pregnancy and with pre-eclampsia. Up-regulation of both GATA3 and TGF-β was observed in pathological placentas, with localization in the villus epithelium (syncytiotrophoblast) stroma and decidua. Our data show altered expression of TGF-β and GATA3, which downstream could lead to a cascade of events that negatively influence trophoblast development and contribute to the pathogenesis of pre-eclampsia.
Topics: Pre-Eclampsia; Humans; Pregnancy; Female; GATA3 Transcription Factor; Placenta; Transforming Growth Factor beta; Adult; Trophoblasts
PubMed: 38759523
DOI: 10.1016/j.tice.2024.102402 -
Results and Problems in Cell... 2024Placentation is the development of a temporary arrangement between the maternal uterus and blastocyst-derived placental tissues designed to transport nutrients, gases,... (Review)
Review
Placentation is the development of a temporary arrangement between the maternal uterus and blastocyst-derived placental tissues designed to transport nutrients, gases, and other products from the mother to the embryo and fetus. Placentation differs histologically among species, but all types of placentation share the common trait of utilizing highly complex cell-to-cell and tissue-to-tissue morphological and biochemical interactions to remodel the uterine-placental interface. An elegant series of electron microscopy (EM) images supports the classification of ovine placentation as synepitheliochorial, because uterine luminal epithelial (LE) cells are maintained at the uterine-placental interface through incorporation into trophoblast syncytial plaques. In this review, we utilize immunofluorescence microscopy to provide further insights into early syncytialization of the ovine placenta. These observations, based on results using immunofluorescence microscopy, complement and expand, not replace, our understanding of syncytialization in sheep.
Topics: Pregnancy; Sheep; Animals; Female; Placenta; Placentation; Trophoblasts; Blastocyst; Fetus
PubMed: 37996676
DOI: 10.1007/978-3-031-37936-9_7 -
IEEE Transactions on Ultrasonics,... Dec 2023The placenta, a highly vascularized interface between the mother and fetus, undergoes dramatic anatomical and functional changes during pregnancy. These changes occur... (Review)
Review
The placenta, a highly vascularized interface between the mother and fetus, undergoes dramatic anatomical and functional changes during pregnancy. These changes occur both during healthy development and adverse pathologies of pregnancy, such as preeclampsia (PE). Abnormal placental development can lead to life-long health impacts on both the mother and child. Photoacoustic (PA) imaging, extensively developed for preclinical imaging applications in oncology and cardiovascular disease, uses optical energy to generate acoustic waves through thermoelastic expansion of light-absorbing chromophores within tissue. Recently, PA imaging has been used to study preclinical placental anatomy and function. If clinical translation of PA imaging of the placenta is achieved, the impact on maternal-fetal health could be expansive. This perspective highlights the recent progress in PA imaging for placental monitoring and discusses the progress needed for human clinical translation.
Topics: Child; Pregnancy; Female; Humans; Placenta; Photoacoustic Techniques; Pre-Eclampsia; Fetus; Spectrum Analysis
PubMed: 37030823
DOI: 10.1109/TUFFC.2023.3263361 -
Reproductive Biology and Endocrinology... Oct 2023Cathepsin C (Cat C) is involved in the inflammatory-immune system and can be degraded by cathepsin D (Cat D). Preeclampsia (PE) and the inflammation-immunity...
BACKGROUND
Cathepsin C (Cat C) is involved in the inflammatory-immune system and can be degraded by cathepsin D (Cat D). Preeclampsia (PE) and the inflammation-immunity relationship is currently a hot research topic, but there are still few studies. The aim was to investigate the expression and significance of Cat C and D in the serum of nonpregnant women, patients in various stages of pregnancy and patients with PE, and in the placenta of patients with normal pregnancy and PE.
METHODS
Sixty young healthy nonpregnant women were selected: 180 normal pregnant women, including 60 each in the first, second, and third trimesters, and 100 women with PE, including 39 women with severe preeclampsia. The levels of Cat C and D in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the expression levels of Cat C and D in placentas were detected by immunohistochemistry (IHC).
RESULTS
The serum of Cat C in the first trimester was significantly lower than that in the nonpregnant group (P < 0.001), whereas Cat D was significantly higher than that in the nonpregnant group (P < 0.01). The levels of Cat C and D in the second trimester and third trimester were significantly higher than those in the first trimester (P < 0.05), but there was no significant difference in Cat C and D between the second trimester and third trimester. The levels of Cat C in the serum and placentas of patients with PE were significantly higher than those in the third trimester (P < 0.001) and positively correlated with the severity of PE (P < 0.001), whereas the levels of Cat D in the serum and placentas of patients with PE were significantly lower than those in the third trimester (P < 0.001) and negatively correlated with the severity of PE (P < 0.001). Age, primigravida proportion, and body mass index were significantly higher in the PE group than in the control group (P < 0.05), which were high-risk factors for PE.
CONCLUSIONS
Cat C and D are associated with the maintenance of normal pregnancy. In patients with preeclampsia, a significant increase in Cat C and a significant decrease in Cat D levels may lead to the occurrence and development of preeclampsia.
Topics: Female; Humans; Pregnancy; Cathepsin C; Cathepsin D; Placenta; Pre-Eclampsia; Pregnancy Trimester, First
PubMed: 37794357
DOI: 10.1186/s12958-023-01138-x -
Archives of Gynecology and Obstetrics Dec 2023
Topics: Female; Humans; Pregnancy; Lipoma; Pelvis; Placenta
PubMed: 37052676
DOI: 10.1007/s00404-023-07039-z