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Search Results (530)

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Keywords = placental function

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16 pages, 1471 KiB  
Article
Alteration in sB7-H4 Serum Levels and Placental Biomarker Expression after Therapeutic Plasma Exchange in Early-Onset Preeclampsia Patients
by Liyan Duan, Yuyang Ma, Beatrix Reisch, Elina Hadrovic, Pawel Mach, Rainer Kimmig, Michael Jahn, Angela Köninger, Antonella Iannaccone and Alexandra Gellhaus
Int. J. Mol. Sci. 2024, 25(20), 11082; https://doi.org/10.3390/ijms252011082 - 15 Oct 2024
Viewed by 244
Abstract
Therapeutic plasma exchange (TPE) is a widely used treatment for numerous diseases including pregnancy-related conditions. Our prior study on 20 early-onset preeclampsia patients undergoing TPE revealed a significant extension in pregnancy duration and reduced serum levels of sFlt-1, sFlt-1/PlGF, and sEndoglin. Here, we [...] Read more.
Therapeutic plasma exchange (TPE) is a widely used treatment for numerous diseases including pregnancy-related conditions. Our prior study on 20 early-onset preeclampsia patients undergoing TPE revealed a significant extension in pregnancy duration and reduced serum levels of sFlt-1, sFlt-1/PlGF, and sEndoglin. Here, we investigated the impact of TPE on serum sB7-H4, an immunological checkpoint molecule, and placental proteins (Flt-1, Eng, B7-H4, iNOS, TNF-α) in TPE-treated early-onset preeclampsia patients (N = 12, 23 + 2–28 + 5 weeks), conventionally treated counterparts (N = 12, 23 + 5–30 weeks), and gestational age-matched controls (N = 8, 22 + 4–31 + 6 weeks). Immunoblotting, ELISA, and co-immunohistochemistry were used for biomarker analysis, including placental inflammation factors (iNOS, TNF-α). The results showed that TPE extended pregnancy by a median of 6.5 days in this cohort of early-onset preeclampsia. Serum sB7-H4, sFlt-1, and sEndoglin levels decreased, along with reduced expression of their membrane-bound proteins in placental tissue upon TPE treatment. Moreover, TPE-treated patients displayed reduced placental inflammation compared to preeclampsia patients receiving standard-of-care treatment. In conclusion, TPE may improve pregnancy outcomes in early-onset preeclampsia by lowering circulating levels of sB7-H4, sFlt-1, and sEndoglin, as well as reducing placental inflammation. This translational approach holds promise for enhancing placental function and extending gestation in high-risk pregnancies including very preterm PE or HELLP cases. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Pregnancy Complications)
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Figure 1
<p>Serum levels of key biomarkers which decreased following therapeutic plasma exchange in early-onset PE patients. Serum levels of sFlt-1 (<b>A</b>), sFlt-1/PlGF (<b>B</b>), sEng (<b>C</b>), and sB7-H4 (<b>D</b>) before and after all the TPE treatment in PE patients. Data represent means ± SD. Significance: * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Serum levels of sFlt-1, sFlt-1/PlGF, and sEng, showing a decreased trend but not statistically significant before and after the first therapeutic plasma exchange in PE patients. Serum levels of sFlt-1 (<b>A</b>), sFlt-1/PlGF (<b>B</b>), sEng (<b>C</b>), and sB7-H4 (<b>D</b>) before and after the first TPE treatment in PE patients. Data represent means ± SD.</p>
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<p>Placental Flt-1, Eng, and B7-H4 protein levels were notably reduced in PE patients treated with TPE compared to those receiving the standard of care treatment. (<b>A</b>) Representative immunoblot images of Flt-1, Eng, and B7-H4 protein expression in the placenta of control (N = 8), PE (N = 12), and PE + TPE (N = 12) patients. The original blots are presented in <a href="#app1-ijms-25-11082" class="html-app">Supplementary Figure S1</a>. (<b>B</b>) Statistical analysis of A to represent the Flt-1 protein levels in placenta. (<b>C</b>) Statistical analysis of A to represent the Eng protein levels in placenta. (<b>D</b>) Statistical analysis of A to represent the B7-H4 protein levels in placenta. Data represent medians ± interquartile ranges with minimum/maximum values as whiskers. Significance: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Placental Flt-1, Eng, and B7-H4 protein levels seem to be decreased in placental villi in PE patients treated with TPE compared to those receiving the standard-of-care treatment. (<b>A</b>–<b>C</b>) Double immunolabeling of Flt-1 (green) and CK7 (red) in placentas from controls and PE patients without and with TPE treatment. The STBs show strong Flt-1 staining in the untreated PE group. (<b>D</b>–<b>F</b>) Double immunolabeling of Eng (green) and CK7 (red), highlighting reduced Eng staining on the basal side of the STB in TPE-treated patients. (<b>G</b>–<b>I</b>) Double immunolabeling of B7-H4 (green) and CK7 (red), with the untreated PE group showing higher B7-H4 expression in the STB. DAPI was used to counterstain DNA (blue). The triangles point to the STB. The scale bar represents 75 μm.</p>
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<p>Placental inflammation was notably reduced in PE patients treated with TPE compared to those receiving the standard-of-care treatment. (<b>A</b>) Representative immunoblot images of TNF-α and iNOS protein expression in the placenta of control (N = 8), PE (N = 12), and PE + TPE (N = 12) patients. (<b>B</b>,<b>C</b>) Statistical analysis of A. (<b>D</b>) Double immunolabeling of iNOS (green) and CK7 (red) in placentas of control, PE, and PE + TPE patients. DAPI was used to counterstain DNA (blue). Data represent medians ± interquartile ranges with minimum/maximum values as whiskers. Significance: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01. The scale bar represents 75 μm.</p>
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<p>Schematic diagram of TPE treatment in early-onset PE. TPE demonstrated efficacy in extending the gestational period for patients with early-onset PE. TPE removes a portion of maternal plasma, replacing it with fresh frozen plasma and/or 4% human albumin, leading to a reduction in these circulating factors. During plasma exchange, there is a notable reduction in the circulating maternal levels of sFlt-1, sEng, and sB7-H4, alongside a corresponding decrease in the membrane-bound proteins (Flt-1, Eng, and B7-H4) within placental tissues, which are the original source of these secreted proteins. This reduction aligns with an amelioration in placental functionality. Specifically, the observed decrease in placental inflammation (iNOS and TNF-α) and cellular apoptosis (cleaved caspase 3), along with the increase in proliferation (Cyclin D1, p21) after TPE treatment, may potentially be associated with the role of B7-H4. Diagram created with BioRender.com.</p>
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12 pages, 2354 KiB  
Article
Vitamin D Receptor—Interplay in COVID-19-Negative, -Infected, and -Vaccinated Women during Pregnancy
by Constantin Condac, Ludmila Lozneanu, Daniela Roxana Matasariu, Alexandra Ursache, Iuliana Elena Bujor, Maria Elena Niță, Vasile Lucian Boiculese, Mihai Sava, Paula Țăroi and Victoria Bîrluțiu
J. Clin. Med. 2024, 13(20), 6140; https://doi.org/10.3390/jcm13206140 (registering DOI) - 15 Oct 2024
Viewed by 355
Abstract
Background: The trophoblast is a significant source of vitamin D synthesis during pregnancy, with the literature suggesting its role in fetal growth. We aim to underline a possible mechanism that would explain negative fetal outcomes in COVID-19-positive mothers by examining the relationship between [...] Read more.
Background: The trophoblast is a significant source of vitamin D synthesis during pregnancy, with the literature suggesting its role in fetal growth. We aim to underline a possible mechanism that would explain negative fetal outcomes in COVID-19-positive mothers by examining the relationship between altered placental structure and function and throphoblast cells‘ vitamin D receptor levels. Methods: The study included 170 placental samples collected from women who gave birth at term without complications, divided into three groups: COVID-19-positive and unvaccinated, COVID-19-negative and vaccinated, and COVID-19-negative and unvaccinated, with exclusion criteria for any other medical complications. Immunohistochemistry (IHC) was performed to detect vitamin D receptor (VDR) expression, and immediate fetal outcomes (weight and Apgar score) were assessed. Results: We found lower gestational age at birth, lower birth weight, and reduced placental VDR (vitamin D receptor) levels in COVID-19-positive women compared to COVID-19-vaccinated and COVID-19-negative women. Conclusions: The presence of the vitamin D receptor in the placenta is related to fetal and placental growth. Its deficiency may contribute to negative fetal outcomes in COVID-19-positive cases. Full article
(This article belongs to the Special Issue New Advances in COVID-19 and Pregnancy)
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<p>Representative histopathological changes in placenta (H&amp;E). (<b>A</b>) COVID-19-positive pregnant women: small, well-vascularized chorionic villi. Syncytial knots and intervillous fibrin (HE × 10). (<b>B</b>) COVID-19-vaccinated pregnant women: chorionic villi, congestion, and fibrosis (HE × 20). (<b>C</b>) COVID-19-negative and unvaccinated pregnant women: different sizes of chorionic villi, congestion, and area of fibrosis (HE × 10).</p>
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<p>Representative images—immunohistochemical visualization of VDR in mononuclear cells of trophoblasts. (<b>A</b>) COVID-19-positive pregnant women (×20). (<b>B</b>) COVID-19-vaccinated pregnant women (×20). (<b>C</b>) COVID-19-negative and unvaccinated pregnant women (×10).</p>
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20 pages, 762 KiB  
Review
Cannabis Use during Pregnancy: An Update
by Angeliki Gerede, Sofoklis Stavros, Christos Chatzakis, Eleftherios Vavoulidis, Panagiota Papasozomenou, Ekaterini Domali, Konstantinos Nikolettos, Efthymios Oikonomou, Anastasios Potiris, Panagiotis Tsikouras and Nikolaos Nikolettos
Medicina 2024, 60(10), 1691; https://doi.org/10.3390/medicina60101691 - 15 Oct 2024
Viewed by 402
Abstract
The use of cannabis during pregnancy has emerged as a mounting cause for concern due to its potential adverse consequences on both the mother and her offspring. This review will focus on the dangers associated with prenatal exposure to cannabis, particularly those related [...] Read more.
The use of cannabis during pregnancy has emerged as a mounting cause for concern due to its potential adverse consequences on both the mother and her offspring. This review will focus on the dangers associated with prenatal exposure to cannabis, particularly those related to neurodevelopment. It will also discuss the features of maternal and placental functioning that are likely to have long-term effects on the offspring’s development. The most pertinent and up-to-date materials can be found through a literature search. The literature emphasizes the substantial hazards associated with prenatal exposure to cannabis. These include impairments in cognitive function and difficulties in behavior in this particular instance. Structural and functional alterations in the brain can be noticed in offspring. The use of cannabis has been associated with an increased likelihood of experiencing pregnancy-related complications, such as giving birth prematurely and having a baby with a low birth weight. Additionally, it has been connected to potential negative effects on mental and emotional well-being. Studies have shown that when a pregnant woman is exposed to cannabis, it can negatively impact the functioning of the placenta and the growth of the fetus. This might potentially contribute to the development of placental insufficiency and restricted growth in the womb. Longitudinal studies reveal that children who were exposed to cannabis in the womb experience additional long-term developmental challenges, such as decreased cognitive abilities, reduced academic performance, and behavioral issues. In order to address the problem of cannabis usage during pregnancy, it is essential to adopt a comprehensive and coordinated strategy. This method should integrate and synchronize public health policy, education, and research initiatives. By implementing these targeted strategies, it is possible to mitigate potential health and welfare concerns for both present and future generations. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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<p>Flow diagram of the selection process of the included studies.</p>
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14 pages, 5396 KiB  
Article
Impaired Endothelium-Dependent Vasodilation and Increased Levels of Soluble Fms-like Tyrosine Kinase-1 Induced by Reduced Uterine Perfusion Pressure in Pregnant Rats: Evidence of Protective Effects with Sodium Nitrite Treatment in Preeclampsia
by Maria Luiza Santos Da Silva, Sáskia Estela Biasotti Gomes, Laisla Zanetoni Martins, Serginara David Rodrigues, Cristal de Jesus Toghi and Carlos Alan Dias-Junior
Int. J. Mol. Sci. 2024, 25(20), 11051; https://doi.org/10.3390/ijms252011051 - 15 Oct 2024
Viewed by 246
Abstract
Preeclampsia (PE) is a hypertensive disorder of pregnancy and is associated with increases in soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) levels. Placental ischemia and hypoxia are hypothesized as initial pathophysiological events of PE. Nitrite (NO metabolite) may be [...] Read more.
Preeclampsia (PE) is a hypertensive disorder of pregnancy and is associated with increases in soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) levels. Placental ischemia and hypoxia are hypothesized as initial pathophysiological events of PE. Nitrite (NO metabolite) may be recycled back to NO in ischemic and hypoxic tissues. Therefore, this study examined the sodium nitrite effects in an experimental model of PE. Pregnant rats received saline (Preg group) or sodium nitrite (Preg + Na-Nitrite group). Pregnant rats submitted to the placental ischemia received saline (RUPP group) or sodium nitrite (RUPP + Na-Nitrite group). Blood pressure, placental and fetal weights, and the number of pups were recorded. Plasma levels of NO metabolites and sFlt-1 were also determined. Vascular and endothelial functions were also measured. Blood pressure, placental and fetal weights, the number of pups, NO metabolites, sFlt-1 levels, vascular contraction, and endothelium-dependent vasodilation in the RUPP + Na-Nitrite rats were brought to levels comparable to those in Preg rats. In conclusion, sodium nitrite may counteract the reductions in NO and increases in sFlt-1 levels induced by the placental ischemia model of PE, thus suggesting that increased blood pressure and vascular and endothelial dysfunctions may be attenuated by sodium nitrite-derived NO. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Treatment of Pregnancy Complications)
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<p>Effects of sodium nitrite on systolic blood pressure (SBP) measured on pregnancy day 21 in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (<span class="html-italic">n</span> = 8–10 animals per group). Values represent the mean ± SEM. <sup>&amp;</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the Preg, RUPP, and RUPP+Na-Nitrite groups; * <span class="html-italic">p</span> &lt; 0.05 vs. the Preg group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the RUPP group.</p>
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<p>Effects of sodium nitrite on placental weight recorded in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (<span class="html-italic">n</span> = 8–10 mothers per group). Values represent the mean ± SEM. <sup>&amp;</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the Preg and RUPP groups; * <span class="html-italic">p</span> &lt; 0.05 vs. the Preg group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the RUPP group.</p>
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<p>Effects of sodium nitrite on fetal weight recorded in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (<span class="html-italic">n</span> = 8–10 mothers per group). Values represent the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. the Preg group; <sup>&amp;</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the Preg and Preg+Na-Nitrite groups; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the RUPP group.</p>
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<p>Effects of sodium nitrite on litter size (total number of pups) noted in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (<span class="html-italic">n</span> = 8–10 mothers per group). Values represent the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. the Preg group; <sup>&amp;</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the Preg and Preg+Na-Nitrite groups; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the RUPP group.</p>
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<p>Effects of sodium nitrite on plasmatic NO metabolites (nitrite+nitrate levels) in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (<span class="html-italic">n</span> = 8–10 animals per group). Values represent the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. the Preg group; <sup>&amp;</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the Preg and Preg+Na-Nitrite groups; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the RUPP group.</p>
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<p>Effects of sodium nitrite on circulating sFlt-1 levels in plasma from the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (<span class="html-italic">n</span> = 8–10 animals per group). Values represent the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. the Preg, Preg+Na-Nitrite, and RUPP+Na-Nitrite groups.</p>
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<p>Effects of sodium nitrite on the vascular reactivity of the thoracic aorta rings in the contraction induced by phenylephrine with (<span class="html-italic">n</span> = 2 rings per animal, (<b>A</b>)) or without (<span class="html-italic">n</span> = 2 rings per animal, (<b>B</b>)) endothelium in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (<span class="html-italic">n</span> = 8–10 animals per group). Values represent the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. the Preg, Preg+Na-Nitrite, and RUPP+Na-Nitrite groups; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 for the RUPP and RUPP+Na-Nitrite vs. the Preg and Preg+Na-Nitrite groups.</p>
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<p>Effects of sodium nitrite on the vascular reactivity of acetylcholine-induced relaxations in the endothelium-intact thoracic aortas (<span class="html-italic">n</span> = 2 rings per animal, (<b>A</b>)) or endothelium-denuded thoracic aortas (<span class="html-italic">n</span> = 2 rings per animal, (<b>B</b>)) or endothelium intact thoracic aortas pre-incubated with L-NAME (<span class="html-italic">n</span> = 2 rings per animal, (<b>C</b>)) in the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (<span class="html-italic">n</span> = 8–10 animals per group). Values represent the mean ± SEM. * <span class="html-italic">p</span> &lt; 0.05 vs. the Preg, Preg+Na-Nitrite, and RUPP+Na-Nitrite groups; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 vs. the Preg group.</p>
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<p>Effects of sodium nitrite on the vascular reactivity of sodium nitroprusside-induced relaxations in the endothelium-intact thoracic aortas (<span class="html-italic">n</span> = 2 rings per animal, (<b>A</b>)) or endothelium-denuded thoracic aortas (<span class="html-italic">n</span> = 2 rings per animal, (<b>B</b>)) from the Preg, Preg+Na-Nitrite, RUPP, and RUPP+Na-Nitrite groups (<span class="html-italic">n</span> = 8–10 animals per group). Values represent the mean ± SEM.</p>
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16 pages, 2333 KiB  
Review
The Research Progress of DNA Methylation in the Development and Function of the Porcine Placenta
by Zhiyuan Zhang, Jiawei Su, Jiaming Xue, Liyao Xiao, Linjun Hong, Gengyuan Cai and Ting Gu
Int. J. Mol. Sci. 2024, 25(19), 10687; https://doi.org/10.3390/ijms251910687 - 4 Oct 2024
Viewed by 506
Abstract
The pig is the most widely consumed domestic animal in China, providing over half of the meat supply in food markets. For livestock, a key economic trait is the reproductive performance, which is significantly influenced by placental development. The placenta, a temporary fetal [...] Read more.
The pig is the most widely consumed domestic animal in China, providing over half of the meat supply in food markets. For livestock, a key economic trait is the reproductive performance, which is significantly influenced by placental development. The placenta, a temporary fetal organ, is crucial for establishing maternal–fetal communication and supporting fetal growth throughout pregnancy. DNA methylation is an epigenetic modification that can regulate the gene expression by recruiting proteins involved in gene silencing or preventing transcription factor binding. To enhance our understanding of the molecular mechanisms underlying DNA methylation in porcine placental development, this review summarizes the structure and function of the porcine placenta and the role of DNA methylation in placental development. Full article
(This article belongs to the Section Molecular Biology)
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<p>Diagram of the structure of the porcine placental barrier: maternal side above the dividing line and fetal side below the dividing line.</p>
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<p>Diagram of the morphologic structure of the pig placenta. Tr: trophoblast; GE: Glandular epithelial cells; BV: blood vessel.</p>
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<p>Diagram of DNA methylation and demethylation mechanisms.</p>
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102 pages, 805 KiB  
Review
Short-Half-Life Chemicals: Maternal Exposure and Offspring Health Consequences—The Case of Synthetic Phenols, Parabens, and Phthalates
by Delphine Rousseau-Ralliard, Jeanne Bozec, Marion Ouidir, Nicolas Jovanovic, Véronique Gayrard, Namya Mellouk, Marie-Noëlle Dieudonné, Nicole Picard-Hagen, Maria-José Flores-Sanabria, Hélène Jammes, Claire Philippat and Anne Couturier-Tarrade
Toxics 2024, 12(10), 710; https://doi.org/10.3390/toxics12100710 - 29 Sep 2024
Viewed by 571
Abstract
Phenols, parabens, and phthalates (PPPs) are suspected or known endocrine disruptors. They are used in consumer products that pregnant women and their progeny are exposed to daily through the placenta, which could affect offspring health. This review aims to compile data from cohort [...] Read more.
Phenols, parabens, and phthalates (PPPs) are suspected or known endocrine disruptors. They are used in consumer products that pregnant women and their progeny are exposed to daily through the placenta, which could affect offspring health. This review aims to compile data from cohort studies and in vitro and in vivo models to provide a summary regarding placental transfer, fetoplacental development, and the predisposition to adult diseases resulting from maternal exposure to PPPs during the gestational period. In humans, using the concentration of pollutants in maternal urine, and taking the offspring sex into account, positive or negative associations have been observed concerning placental or newborn weight, children’s BMI, blood pressure, gonadal function, or age at puberty. In animal models, without taking sex into account, alterations of placental structure and gene expression linked to hormones or DNA methylation were related to phenol exposure. At the postnatal stage, pollutants affect the bodyweight, the carbohydrate metabolism, the cardiovascular system, gonadal development, the age of puberty, sex/thyroid hormones, and gamete quality, but these effects depend on the age and sex. Future challenges will be to explore the effects of pollutants in mixtures using models and to identify the early signatures of in utero exposure capable of predicting the health trajectory of the offspring. Full article
(This article belongs to the Section Reproductive and Developmental Toxicity)
14 pages, 6064 KiB  
Article
Hypothermically Stored Amnion Is Robust and Provides a Scaffold for Supporting Wound Healing by Retaining the Characteristics of Native Tissue
by Katrina A. Harmon, Kelly A. Kimmerling, Justin T. Avery and Katie C. Mowry
Int. J. Mol. Sci. 2024, 25(19), 10347; https://doi.org/10.3390/ijms251910347 - 26 Sep 2024
Viewed by 341
Abstract
Placental-derived products have been used since the early 1900s for wound applications and have shown clinical utility in supporting wound healing. A hypothermically stored amniotic membrane (HSAM) was developed using a proprietary process to allow for the retention of the extracellular matrix (ECM), [...] Read more.
Placental-derived products have been used since the early 1900s for wound applications and have shown clinical utility in supporting wound healing. A hypothermically stored amniotic membrane (HSAM) was developed using a proprietary process to allow for the retention of the extracellular matrix (ECM), viable cells, and key proteins. To evaluate its utility, we characterized the HSAM and compared it to a native unprocessed amniotic membrane (uAM) and a dehydrated amniotic membrane (dAM), as well as assessing the functionality of the HSAM as a scaffold to promote cell growth. The HSAM, uAM, and dAM were compared using scanning electron microscopy (SEM), histology, and thickness. Scaffold durability was assessed in vitro using mechanical testing and a simulated wound fluid (SWF) model. The ability of the HSAM to act as a scaffold was evaluated using an in vitro attachment model. The HSAM showed similar structural characteristics compared to the uAM; however, the dAM was significantly more compact. There were no significant differences between the HSAM and the uAM following degradation in an SWF model. ECM- and placental-related proteins were shared between the HSAM and uAM, and the HSAM enhanced the attachment and proliferation of fibroblasts in vitro. The HSAM is substantially similar to the uAM by retaining key regulatory proteins, resisting degradation in SWF, and acting as a scaffold for cellular growth and invasion. Full article
(This article belongs to the Special Issue Recent Advances in Wound Healing: 2nd Edition)
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<p>Characterization of tissues by scanning electron microscopy (SEM) and histology. Representative SEM images of the (<b>A</b>) epithelial and (<b>B</b>) stromal layers, along with (<b>C</b>) a cross-sectional view. (<b>D</b>) Representative hematoxylin and eosin (H&amp;E) staining of tissues. Magnification for SEM = 600×; H&amp;E = 20×; scale bars for images are 50 µm. uAM: unprocessed amniotic membrane; HSAM: hypothermically stored amniotic membrane; dAM: dehydrated amniotic membrane; arrow: epithelial layer; S: spongy layer.</p>
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<p>Characterization of tissues by thickness measurements and tensile testing. (<b>A</b>) Total thickness measurements in the uAM, HSAM, and dAM following processing. (<b>B</b>) Maximum displacement and (<b>C</b>) maximum force for the uAM and HSAM. Average ± standard deviation reported; **** denotes <span class="html-italic">p</span> &lt; 0.0001. uAM: unprocessed amniotic membrane; HSAM: hypothermically stored amniotic membrane; dAM: dehydrated amniotic membrane; ns: not significant.</p>
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<p>Durability of tissues in simulated wound fluid (SWF). (<b>A</b>) Tissue weight of remaining tissue and (<b>B</b>) rate of degradation after 17 days in SWF. Representative scanning electron microscopy (SEM) images of changes in the (<b>C</b>) epithelial and (<b>D</b>) stromal layers following degradation in SWF. Average ± standard deviation reported; * denotes <span class="html-italic">p</span> &lt; 0.05. Magnification for SEM = 200×; scale bars for images are 200 µm. uAM: unprocessed amniotic membrane; HSAM: hypothermically stored amniotic membrane.</p>
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<p>Characterization ECM properties and functionality as a scaffold. Representative (<b>A</b>) Masson’s Trichrome staining and immunohistochemistry (IHC) of relevant extracellular matrix markers and (<b>B</b>) IHC of relevant placental-related growth factors. Magnification for Masson’s Trichrome, IHC, and H&amp;E: 20×; scale bars for all images are 50 µm. uAM: unprocessed amniotic membrane; HSAM: hypothermically stored amniotic membrane; arrow: epithelial layer; S: spongy layer; HGF: hepatocyte growth factor; IGF-1: insulin-like growth factor 1; TGF-β1: transforming growth factor beta 1.</p>
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<p>Fibroblast attachment and proliferation following seeding with human dermal fibroblasts (NHDF) and mouse fibroblasts (L929) onto hypothermically stored amniotic membranes. Cell number from AlamarBlue assessment showing metabolic activity of NHDFs (<b>A</b>) and L929s (<b>B</b>). (<b>C</b>) Representative immunofluorescence staining of seeded and non-seeded scaffolds at day 3 and 14; 40× magnification. Average ± standard deviation reported; ns denotes not significant; * denotes <span class="html-italic">p</span> &lt; 0.05; ** denotes <span class="html-italic">p</span> &lt; 0.01; *** denotes <span class="html-italic">p</span> &lt; 0.001; **** denotes <span class="html-italic">p</span> &lt; 0.0001 compared to non-seeded controls. Blue: nuclei; green: TGF-β1; red: f-actin (phalloidin); arrow: epithelial layer; S: spongy layer; Scale bar: 25 µm.</p>
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<p>Structural characterization of fibroblasts seeded onto hypothermically stored amniotic membranes. Representative scanning electron microscopy images of non-seeded and human fibroblasts seeded (<b>A</b>) and mouse fibroblast seeded (<b>B</b>) grafts. For SEM, representative images are at 100× (scale bar: 500 µm) and 500× (scale bar: 100 µm).</p>
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18 pages, 8177 KiB  
Article
Combining Transcriptomics and Proteomics to Screen Candidate Genes Related to Bovine Birth Weight
by Xiuyuan Wang, Ruili Liu, Zhenpeng Chen, Renzheng Zhang, Yanfang Mei, Xiuping Miao, Xuejin Bai and Yajuan Dong
Animals 2024, 14(18), 2751; https://doi.org/10.3390/ani14182751 - 23 Sep 2024
Viewed by 532
Abstract
The placenta is a vital organ in bovine reproduction, crucial for blood supply, nutrient transport, and embryonic development. It plays an essential role in the intrauterine growth of calves. However, the molecular mechanisms governing placental function in calves remain inadequately understood. Methods: We [...] Read more.
The placenta is a vital organ in bovine reproduction, crucial for blood supply, nutrient transport, and embryonic development. It plays an essential role in the intrauterine growth of calves. However, the molecular mechanisms governing placental function in calves remain inadequately understood. Methods: We established transcriptome and proteome databases for low-birth-weight (LB) and high-birth-weight (HB) calf placentae, identifying key genes and proteins associated with birth weight through bioinformatics analyses that included functional enrichment and protein–protein interactions (PPIs). Both mRNA and protein levels were validated. Results: A total of 1494 differentially expressed genes (DEGs) and 294 differentially expressed proteins (DEPs) were identified when comparing the LB group to the HB group. Furthermore, we identified 53 genes and proteins exhibiting significant co-expression across both transcriptomic and proteomic datasets; among these, 40 were co-upregulated, 8 co-downregulated, while 5 displayed upregulation at the protein level despite downregulation at the mRNA level. Functional enrichment analyses (GO and KEGG) and protein–protein interaction (PPI) analysis indicate that, at the transcriptional level, the primary factor contributing to differences in calf birth weight is that the placenta of the high-birth-weight (HB) group provides more nutrients to the fetus, characterized by enhanced nutrient transport (SLC2A1 and SLC2A11), energy metabolism (ACSL1, MICALL2, PAG2, COL14A1, and ELOVL5), and lipid synthesis (ELOVL5 and ELOVL7). In contrast, the placenta of the low-birth-weight (LB) group prioritizes cell proliferation (PAK1 and ITGA3) and angiogenesis. At the protein level, while the placentae from the HB group exhibit efficient energy production and lipid synthesis, they also demonstrate reduced immunity to various diseases such as systemic lupus erythematosus and bacterial dysentery. Conversely, the LB group placentae excel in regulating critical biological processes, including cell migration, proliferation, differentiation, apoptosis, and signal transduction; they also display higher disease immunity markers (COL6A1, TNC CD36, CD81, Igh-1a, and IGHG) compared to those of the HB group placentae. Co-expression analysis further suggests that increases in calf birth weight can be attributed to both high-efficiency energy production and lipid synthesis within the HB group placentae (ELOVL5, ELOVL7, and ACSL1), alongside cholesterol biosynthesis and metabolic pathways involving CYP11A1 and CYP17A1. Conclusion: We propose that ELOVL5, ELOVL7, ACSL1, CYP11A1, and CYP17A1 serve as potential protein biomarkers for regulating calf birth weight through the modulation of the fatty acid metabolism, lipid synthesis, and cholesterol levels. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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<p>Phenotypes of the placenta and fetus. (<b>A</b>) Placenta and neonates from the LB group (left) and HB group (right). (<b>B</b>) Bar chart of the neonate phenotype data. (<b>C</b>) Statistical bar chart of the placental phenotype data. A <span class="html-italic">t</span> test was used, with * indicating <span class="html-italic">p</span> &lt; 0.05 and ns indicating no statistically significant difference. The birth weight, thigh circumference, and chest circumference of the HB litter were significantly higher than those of the LB litter (<span class="html-italic">p</span> &lt; 0.05). This suggests that the HB neonates have greater intrauterine development. The placental weight, length, and thickness in the HB group were significantly higher than those in the LB group (<span class="html-italic">p</span> &lt; 0.05), but there was no significant difference in the placental width.</p>
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<p>Comparison of the DEGs and DEPs between the LB and HB calves. (<b>A</b>) Principal component analysis of all quantitative RNA. (<b>B</b>) DEGs volcano map. (<b>C</b>) Principal component analysis of all quantitative protein. (<b>D</b>) DEPs volcano map. (<b>E</b>) Intra-transcriptome correlation heat map. (<b>F</b>) DEGs heat map. (<b>G</b>) Intra-proteome correlation heat map. (<b>H</b>) DEPs heat map. In (<b>B</b>,<b>D</b>), a red dot indicates that the <span class="html-italic">p</span>-value and log2(FC) of the DEGs/DEPs reached the threshold, a green dot indicates that the log2(FC) of the DEGs/DEPs reached the threshold, and a blue dot indicates that the <span class="html-italic">p</span>-value of the DEGs/DEPs reached the threshold. Gray dots indicate insignificant differences. A total of 1494 DEGs and 294 DEPs were detected. There were 1036 upregulated genes and 217 upregulated proteins. There were 458 downregulated genes and 77 downregulated proteins. The <span class="html-italic">x</span>-axis represents the log2(fold change) and the <span class="html-italic">y</span>-axis represents the −log10 (<span class="html-italic">p</span>-value). The dashed line represents the threshold (fold change &gt; 1.5, <span class="html-italic">p</span> &lt; 0.05), plotted according to its log2(fold change) and −log10 (<span class="html-italic">p</span>-value). For (<b>E</b>,<b>G</b>), each column and row in the graph represents a sample; the bluer the color, the higher the correlation; the yellower the color, the lower the correlation. For (<b>F</b>,<b>H</b>), each column in the figure represents a sample, and each row represents a gene. The expression levels of the genes in the different samples are indicated by different colors. The redder the color, the higher the expression level, and the greener the color, the lower the expression level.</p>
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<p>GO and KEGG pathways are enriched. (<b>A</b>,<b>B</b>) GO (left) and KEGG (right) enrichment analysis of up- and downregulated DEGs. (<b>C</b>,<b>D</b>) GO (left) and KEGG enrichment analysis of up- and downregulated DEPs (right). For the GO enrichment analysis diagram, the <span class="html-italic">x</span>-axis represents the gene count and the −log10 (<span class="html-italic">p</span>-value); the <span class="html-italic">y</span>-axis represents the names of the gene enrichment GO classes. Blue represents the biological process category, orange represents the cell component category, and green represents the molecular function category. For the KEGG enrichment analysis diagram, the <span class="html-italic">y</span>-axis represents the name of the KEGG class for the pathways, and the <span class="html-italic">x</span>-axis represents the Rich factor. The size of the dots corresponds to the count, as shown in the legend.</p>
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<p>Correlation analysis between the proteomics and transcriptomics data. (<b>A</b>) The Venn diagram of the DEGs/DEPs. Pink represents the downregulated DEPs, lighter blue represents the upregulated DEPs, darker blue represents the upregulated DEGs, and light green represents the downregulated DEGs. A total of 53 pairs of DEGs/DEPs displayed discrepancies in the LB vs. HB fetal calf comparison (mRNA and protein levels), which were classified into 40 upregulated and 8 downregulated. (<b>B</b>) Nine quadrant diagrams. Different points represent genes/proteins with different expression trends. Gray indicates the non-overlapping genes/proteins. Red represents the significant differences in protein and gene expression, green represents the differences in protein expression, and blue represents the differences in transcriptional expression. (<b>C</b>) The significant pathways of co-expressed DEGs/DEPs. The <span class="html-italic">y</span>-axis represents the names of the gene-enriched KEGG categories, and the <span class="html-italic">x</span>-axis represents the Rich factor. The genes in the pathway are shown on the left. (<b>D</b>) The GO enrichment analysis of the co-expressed DEGs/DEPs. The <span class="html-italic">x</span>-axis represents gene count and −log10 (<span class="html-italic">p</span>-value); the <span class="html-italic">y</span>-axis represents the names of the gene enrichment GO classes. (<b>E</b>) Predicted regulatory PPI networks based on the shared co-expressed DEGs/DEPs with the same trend and their potential targeted genes. The confidence level is 0.7. The red exhibits the upregulated DEGs/DEPs and the blue exhibits the downregulated DEGs/DEPs.</p>
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<p>Data validation through qRT-PCR and Western blot. (<b>A</b>) Comparison of the 16 mRNAs using qRT-PCR and RNA-Seq, where the orange reflects the qRT-PCR outcomes and the blue indicates the RNA-Seq outcomes. The <span class="html-italic">x</span>-axis represents the names of the genes, and the <span class="html-italic">y</span>-axis represents the log2(FC). (<b>B</b>–<b>D</b>) The Western blot results analysis of PAK1 and ITGA3 in different groups. Values are expressed as means ± SEM (<span class="html-italic">n</span> = 3). The left <span class="html-italic">y</span>-axis is the protein expression, the right <span class="html-italic">y</span>-axis is the FPKM value, and the <span class="html-italic">x</span>-axis is the grouping. <span class="html-italic">ACSL1</span>, acyl-CoA synthetase long-chain family member 1; <span class="html-italic">ELOVL5</span>, ELOVL fatty acid elongase 5; <span class="html-italic">ELOVL7</span>, ELOVL fatty acid elongase 7; <span class="html-italic">IQGAP2</span>, IQ motif containing GTPase-activating protein 2; <span class="html-italic">ITGA3</span>, integrin subunit alpha 3; <span class="html-italic">PAK1</span>, p21 (RAC1)-activated kinase 1; <span class="html-italic">CYP11A1</span>, cytochrome P450 family 11 subfamily A member 1; <span class="html-italic">CYP17A1</span>, cytochrome P450 family 17 subfamily A member 1; <span class="html-italic">PDLIM1</span>, PDZ and LIM domain 1; <span class="html-italic">TMAB4X</span>, thymosin beta 4 X-linked; <span class="html-italic">COL14A1</span>, collagen type XIV alpha 1 chain; <span class="html-italic">SERPINH1</span>, serpin family H member 1; <span class="html-italic">CD81</span>, CD81 molecule; <span class="html-italic">SLC23A2</span>, solute carrier family 23 member 2; <span class="html-italic">TAGLN</span>, transgelin; <span class="html-italic">S100A13</span>, S100 calcium-binding protein A13.</p>
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12 pages, 11776 KiB  
Article
Shedding Light on the COVID-19 Pandemic: Placental Expression of Cell Biomarkers in Negative, Vaccinated, and Positive Pregnant Women
by Constantin Condac, Ludmila Lozneanu, Daniela Roxana Matasariu, Alexandra Ursache, Iuliana Elena Bujor, Maria Elena Niță, Vasile Lucian Boiculese and Victoria Bîrluțiu
J. Clin. Med. 2024, 13(18), 5546; https://doi.org/10.3390/jcm13185546 - 19 Sep 2024
Viewed by 494
Abstract
Background: We investigated the expression of inflammation, placental development, and function markers, including cluster of differentiation 44 (CD44), osteopontin (OPN), and cyclooxygenase-2 (COX-2), to shed light on the controversy regarding the impact of the COVID-19 epidemic on fetal development and pregnancy outcomes. [...] Read more.
Background: We investigated the expression of inflammation, placental development, and function markers, including cluster of differentiation 44 (CD44), osteopontin (OPN), and cyclooxygenase-2 (COX-2), to shed light on the controversy regarding the impact of the COVID-19 epidemic on fetal development and pregnancy outcomes. Methods: We immunohistochemically analyzed placental tissue from 170 patients (65 COVID-positive and unvaccinated women; 35 Pfeizer-vaccinated and COVID-negative women; and 70 COVID-negative and unvaccinated women, without any other associated pathology) for particularities in the expression of these three molecules. Results: CD44 expression was highest in COVID-negative and unvaccinated women, moderate in COVID-positive cases, and lowest in vaccinated and COVID-negative women. OPN expression was highest in COVID-negative and Pfeizer-vaccinated cases, moderate in COVID-negative and unvaccinated cases, and lowest in COVID-positive cases. COX-2 expression was increased in COVID-negative and unvaccinated women, modestly elevated in COVID-positive and unvaccinated cases, and lowest in vaccinated cases. Conclusions: These findings reflected an alteration in the placental structure and consequent function due to altered expression of the three studied molecules. Full article
(This article belongs to the Special Issue New Advances in COVID-19 and Pregnancy)
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<p>Flow chart of our included cases.</p>
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<p>Representative histopathological changes in the placenta (HE). (<b>A</b>) COVID-19-positive pregnant women: small, well-vascularized chorionic villi. Syncytial knots and intervillous fibrin (HEx10). (<b>B</b>) COVID-19-vaccinated pregnant women: chorionic villi, congestion, and fibrosis (HEx20). (<b>C</b>) COVID-19-negative and unvaccinated pregnant women: different size of chorionic villi, congestion, and area of fibrosis (HEx10).</p>
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<p>Representative immunohistochemical analysis of CD44, OPN, and anti-COX-2 in trophoblastic mononuclear cells. The arrows indicate positive staining. (<b>A</b>) COVID-19-positive pregnant women (×20). (<b>B</b>) COVID-19-vaccinated pregnant women (×20). (<b>C</b>) COVID-19-negative and unvaccinated pregnant women (×20). (<b>D</b>) COVID-19-positive pregnant women (×20). (<b>E</b>) COVID-19-vaccinated pregnant women (×20). (<b>F</b>) COVID-19-negative and unvaccinated pregnant women (×20). (<b>G</b>) COVID-19-posietive pregnant women (×20). (<b>H</b>) COVID-19-vaccinated pregnant women (×20). (<b>I</b>) COVID-19-negative and unvaccinated pregnant women (×20).</p>
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<p>Scatterplots representing the correlations between our three biomarkers.</p>
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27 pages, 12992 KiB  
Article
ITRAQ Based Proteomics Reveals the Potential Mechanism of Placental Injury Induced by Prenatal Stress
by Yujie Li, Junlin Hou, Liping Yang, Tong Zhang, Yu Jiang, Zhixing Du, Huizi Ma, Gai Li, Jianghui Zhu and Ping Chen
Int. J. Mol. Sci. 2024, 25(18), 9978; https://doi.org/10.3390/ijms25189978 - 16 Sep 2024
Viewed by 670
Abstract
Maternal stress experienced during prenatal development is recognized as a significant risk factor for neurodevelopmental and neuropsychiatric disorders across the offspring’s lifespan. The placental barrier serves a crucial function in safeguarding the fetus from detrimental exposures during gestation. However, previous investigations have not [...] Read more.
Maternal stress experienced during prenatal development is recognized as a significant risk factor for neurodevelopmental and neuropsychiatric disorders across the offspring’s lifespan. The placental barrier serves a crucial function in safeguarding the fetus from detrimental exposures during gestation. However, previous investigations have not yet comprehensively elucidated the extensive connections between prenatal stress and the expression of placental proteins. In this study, we used iTRAQ-based quantitative proteomics to elucidate the placental adaptive mechanisms of pregnant rats in response to fear-induced stress. Our results showed that during pregnancy, exposure to fear-induced stress led to a pathological hypercoagulable state in the mother’s body. Placental circulation was also disrupted, significantly reducing placental efficiency and blood oxygen saturation in newborn rats. Proteomic analyses showed that most of the DEPs were annotated to the PI3K-Akt and ECM-receptor interaction signaling pathway. In addition, the expressions of CDC37, HSP90β, AKT, p-AKT and p-mTOR were down-regulated significantly in the placenta. Our results demonstrated that prenatal fear-induced stress led to inhibition of the cellular signal transduction of placental PI3K/AKT/mTOR, which affected biological processes such as rRNA processing, translation, protein folding, protein stability, and oxygen transport in the placenta. These abnormalities in biological functions could potentially damage the barrier function of the placenta and thereby result in abnormal development in the offspring. Full article
(This article belongs to the Collection Feature Papers in Molecular Informatics)
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Graphical abstract
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<p>Behavioral assessment of pregnant rats and their pups. The results of (<b>A</b>) the Sucrose Preference Test and the immobility time of pregnant rats are presented. (<b>B</b>) The results of Open-Field Test of pregnant rats. (<b>C</b>) The concentrations of serum stress hormones in pregnant rats. (<b>D</b>) The physical and reflex development of offspring. (<b>E</b>) The sucrose consumption and the immobility times in the Tail suspension test of pups. (<b>F</b>) The escape latency during the 4 training days in the MWM and (<b>G</b>) the swimming speeds, the retention time that rats spent in the target quadrant, and the number of times that the pups crossed the original platform during the probe test in the MWM. (<b>H</b>) The frequency of ambulation, rearing, and self-grooming in the open field-tests of the pups. (<b>I</b>) The result of the average litter size of pregnant rats. NC group, normal control group; FSM group, fear stress model group; SP, Sucrose Preference; IT, immobility time; AF, Ambulation frequency: number of floor units entered with all four feet; RF, Rearing frequency, number of instances of standing on the hindlimbs without touching the wall; SF, Self-grooming frequency: number of self-grooming actions performed; ACTH, Adrenocorticotropic hormone; CORT, Corticosterone; OFSM, offspring from the FSM group; ONC, offspring from the normal control group; EYO, eye opening; EAO, ear opening; IE, incisor eruption; ASR, auditory startle reflex; SRR, surface righting reflex; MWM, Morris water maze. Values are expressed as means ± standard deviations.* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 versus NC group or ONC group.</p>
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<p>Effects of prenatal fear stress on placental efficiency, coagulatory biomarkers, and placental histopathology in pregnant rats. (<b>A</b>) the morphological features of placental tissues; (<b>B</b>) the diameters and (<b>C</b>) the thicknesses of placentas; (<b>D</b>) the weights of the fetus and placentas, and the placental efficiency; (<b>E</b>) the blood oxygen saturations of pregnant rats and their pups; (<b>F</b>) quantification of red blood cells in placental blood vessels using imageJ; (<b>G</b>,<b>H</b>) the coagulatory biomarkers of pregnant rats using the detection kits; (<b>I</b>) Quantitative analysis of the vascular network distribution in placental tissue using imageJ; (<b>J</b>) the H&amp;E staining and Masson staining of the placentas were performed to evaluate the pathological changes of the placenta. The arrow indicates the presence of red blood cells within the blood vessels. NC group, normal control group; FSM group, fear stress model group; OFSM, offspring from the FSM group; ONC, offspring from the normal control group; PND 21, postnatal days of 21, PT, prothrombin time; APTT, activated partial thromboplastin time; TT, thrombin time; FIB, fibrinogen; ATIII, antithrombin III. Values are expressed as means ± standard deviations.* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 versus NC group or ONC group.</p>
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<p>The volcano map of the identified proteins and GO classification of DEPs were shown. (<b>A</b>) The volcano map of the identified proteins was plotted based on its logarithmic fold change and <span class="html-italic">p</span>-value. <span class="html-italic">x</span>-axis represents the log2-fold change of protein expressions in FSM group compared to the NC group; The <span class="html-italic">y</span>-axis corresponds to the <span class="html-italic">p</span>-value of this fold change. Red dots: significant difference proteins; blue dots: proteins with fold changes &gt; 0.83 or &lt;1.2, and <span class="html-italic">p</span>-value &lt; 0.05; grey and green dots: proteins with no significant difference in expression. (<b>B</b>–<b>D</b>) the GO classification of DEPs; (<b>B</b>) distributions of the DEPs for cellular components; (<b>C</b>) distributions of the DEPs for molecular functions; (<b>D</b>) distributions of the DEPs for biological processes. Only the top 20 Gene Ontology (GO) terms with significant differences (<span class="html-italic">p</span>-value &lt; 0.05) are shown.</p>
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<p>PPI network construction and hub genes extraction of DEPs. (<b>A</b>) The PPI network of the DEPs is shown. Network nodes represent proteins; edges represent protein–protein associations. Network analysis was set at high confidence (STRING score = 0.4) and high FDR stringency (0.01). Red indicates significantly increased; green indicates significantly decreased; width represents the degree of the interactions. (<b>B</b>) The top 10 hub genes were extracted with cytoHubba plug-in of Cytoscape software, and the eight algorithms are shown. Network nodes represent proteins; edges represent protein–protein associations. Color represents the score. MCC, Matthews Correlation Coefficient; DMNC, Neighborhood Component Centrality; MNC, Maximum Neighbor Connectivity; EPC, Edge Percolated Component.</p>
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<p>The results of KEGG enrichment of DEPs. (<b>A</b>) The significantly enriched pathways (<span class="html-italic">p</span>-value &lt; 0.05). (<b>B</b>) The significant interactions of the pathways (<span class="html-italic">p</span>-value &lt; 0.05). Circle-nodes represent DEPs. Arrow-shaped nodes represent the pathways. Edges represent connections between the nodes. Node color represents the pathways to which they belong. Yellow coloring represents the multiple pathways to which the proteins belong.</p>
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<p>The expressions of PI3K/AKT/mTOR pathway in the placenta of rats detected by western blotting assay. (<b>A</b>) Representative western blotting images of PI3K, AKT, and p-AKT; (<b>B</b>) Representative western blotting images of mTOR and p-mTOR. The protein expressions of PI3K (<b>C</b>), AKT (<b>D</b>), and p-AKT (<b>E</b>) determined by image J software (1.53n); (<b>F</b>) The p-AKT/AKT ratio calculated. The protein expressions of mTOR (<b>G</b>) and p-mTOR (<b>H</b>) determined by image J software (1.53n); (<b>I</b>) The p-mTOR/mTOR ratio calculated. (J) Representative western blotting images of CDC37 and HSP90β. The protein expressions of CDC37 (<b>K</b>), and HSP90β (<b>L</b>) determined by image J software (1.53n). Results presented as means ± SD (<span class="html-italic">n</span> = 6). ** <span class="html-italic">p</span> &lt; 0.01 and * <span class="html-italic">p</span> &lt; 0.05 versus ONC group.</p>
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<p>Schematic diagrams for prenatal stress-induced placental damage. Prenatal fear stress induces down-regulation of PI3K/AKT/mTOR pathway in placenta. These abnormalities in protein expression might damage the barrier function of the placenta and thereby cause abnormal development in the offspring.</p>
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<p>Fear stress schema illustration.</p>
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<p>Schematic diagrams for the experimental protocol.</p>
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27 pages, 1318 KiB  
Review
Impact of Ionizing Radiation Exposure on Placental Function and Implications for Fetal Programming
by Cameron Hourtovenko, Shayen Sreetharan, Sujeenthar Tharmalingam and T. C. Tai
Int. J. Mol. Sci. 2024, 25(18), 9862; https://doi.org/10.3390/ijms25189862 - 12 Sep 2024
Viewed by 650
Abstract
Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and [...] Read more.
Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta’s role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta’s role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta’s crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential. Full article
(This article belongs to the Special Issue The Effect of Ionizing Radiation on Human Cells)
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<p>An anatomical diagram of the matured mouse placenta. Metrial gland (MG), decidua (DA), basal zone (BZ), labyrinth zone (LZ), and chorionic plate (CP). Created in BioRender. Hourtovenko, C. (2024) <a href="http://BioRender.com/x27s327" target="_blank">BioRender.com/x27s327</a> (accessed on 10 September 2023).</p>
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11 pages, 759 KiB  
Review
The Role of the Endometrium in Implantation: A Modern View
by Pavel I. Deryabin and Aleksandra V. Borodkina
Int. J. Mol. Sci. 2024, 25(17), 9746; https://doi.org/10.3390/ijms25179746 - 9 Sep 2024
Viewed by 673
Abstract
According to the current data, the endometrium acts as a “sensor” of embryo quality, which promotes the implantation of euploid embryos and prevents the implantation and/or subsequent development of genetically abnormal embryos. The present review addresses the nature of the “sensory function” of [...] Read more.
According to the current data, the endometrium acts as a “sensor” of embryo quality, which promotes the implantation of euploid embryos and prevents the implantation and/or subsequent development of genetically abnormal embryos. The present review addresses the nature of the “sensory function” of the endometrium and highlights the necessity for assessing its functional status. The first section examines the evolutionary origin of the “sensory” ability of the endometrium as a consequence of spontaneous decidualization that occurred in placental animals. The second section details the mechanisms for implementing this function at the cellular level. In particular, the recent findings of the appearance of different cell subpopulations during decidualization are described, and their role in implantation is discussed. The pathological consequences of an imbalance among these subpopulations are also discussed. Finally, the third section summarizes information on currently available clinical tools to assess endometrial functional status. The advantages and disadvantages of the approaches are emphasized, and possible options for developing more advanced technologies for assessing the “sensory” function of the endometrium are proposed. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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<p>Schematic dendrogram reflecting the emergence of spontaneous decidualization during the evolution of mammals (adapted from [<a href="#B16-ijms-25-09746" class="html-bibr">16</a>]).</p>
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<p>Dynamics of decidualization of endometrial stromal cells (EnSC) relative to the progression of the menstrual and ovarian cycles in humans.</p>
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31 pages, 440 KiB  
Review
Nutraceuticals in Pregnancy: A Special Focus on Probiotics
by Angelica Perna, Noemi Venditti, Francesco Merolla, Sabato Fusco, Germano Guerra, Stefano Zoroddu, Antonio De Luca and Luigi Bagella
Int. J. Mol. Sci. 2024, 25(17), 9688; https://doi.org/10.3390/ijms25179688 - 7 Sep 2024
Viewed by 974
Abstract
The placenta is crucial to fetal development and performs vital functions such as nutrient exchange, waste removal and hormone regulation. Abnormal placental development can lead to conditions such as fetal growth restriction, pre-eclampsia and stillbirth, affecting both immediate and long-term fetal health. Placental [...] Read more.
The placenta is crucial to fetal development and performs vital functions such as nutrient exchange, waste removal and hormone regulation. Abnormal placental development can lead to conditions such as fetal growth restriction, pre-eclampsia and stillbirth, affecting both immediate and long-term fetal health. Placental development is a highly complex process involving interactions between maternal and fetal components, imprinted genes, signaling pathways, mitochondria, fetal sexomes and environmental factors such as diet, supplementation and exercise. Probiotics have been shown to make a significant contribution to prenatal health, placental health and fetal development, with associations with reduced risk of preterm birth and pre-eclampsia, as well as improvements in maternal health through effects on gut microbiota, lipid metabolism, vaginal infections, gestational diabetes, allergic diseases and inflammation. This review summarizes key studies on the influence of dietary supplementation on placental development, with a focus on the role of probiotics in prenatal health and fetal development. Full article
12 pages, 521 KiB  
Review
Hydroxychloroquine as an Adjunct Therapy for Diabetes in Pregnancy
by Nurul Iftida Basri, Padma Murthi and Rahana Abd Rahman
Int. J. Mol. Sci. 2024, 25(17), 9681; https://doi.org/10.3390/ijms25179681 - 6 Sep 2024
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Abstract
This review discusses the pathophysiology of diabetes in pregnancy in relation to the placental function. We review the potential use of hydroxychloroquine in improving pregnancy outcomes affected by diabetes. The review focuses on the mechanism of action of hydroxychloroquine and its potential effects [...] Read more.
This review discusses the pathophysiology of diabetes in pregnancy in relation to the placental function. We review the potential use of hydroxychloroquine in improving pregnancy outcomes affected by diabetes. The review focuses on the mechanism of action of hydroxychloroquine and its potential effects on diabetes. There are several pathways in which hydroxychloroquine mediates its effects: through the inflammasome complex, inflammatory cytokines, oxidative stress, modulatory effects, and antihyperglycemic effects. As a safe drug to be used in pregnancy, it is worth exploring the possible use hydroxychloroquine as an adjunct treatment to the current therapy of diabetes in pregnancy. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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<p>Inflammasomes—mediators of inflammation and diabetes. The activation of the inflammasome complex NLRP3 occurs when DAMPs (such as ROS) interact with Toll-like receptors (TLRs) and activate nuclear factor-kB (NFκβ) [<a href="#B31-ijms-25-09681" class="html-bibr">31</a>,<a href="#B32-ijms-25-09681" class="html-bibr">32</a>,<a href="#B33-ijms-25-09681" class="html-bibr">33</a>,<a href="#B34-ijms-25-09681" class="html-bibr">34</a>,<a href="#B35-ijms-25-09681" class="html-bibr">35</a>,<a href="#B36-ijms-25-09681" class="html-bibr">36</a>]. Caspase-1 activation then ensues, leading to the production of pro-inflammatory cytokines and eventual placental inflammation in diabetes [<a href="#B32-ijms-25-09681" class="html-bibr">32</a>,<a href="#B33-ijms-25-09681" class="html-bibr">33</a>,<a href="#B34-ijms-25-09681" class="html-bibr">34</a>,<a href="#B35-ijms-25-09681" class="html-bibr">35</a>]. Targeting the pathway with HCQ may inhibit (red sign showing inhibition) the activation of TLRs or NLRs and mitigate the innate immune signaling which leads to the pathophysiology of diabetes in pregnancy.</p>
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Article
Dietary Supplementation with 25-Hydroxyvitamin D3 on Reproductive Performance and Placental Oxidative Stress in Primiparous Sows during Mid-to-Late Gestation
by Jing Li, Qingyue Bi, Yu Pi, Xianren Jiang, Yanpin Li and Xilong Li
Antioxidants 2024, 13(9), 1090; https://doi.org/10.3390/antiox13091090 - 6 Sep 2024
Viewed by 638
Abstract
The placenta plays a crucial role in nutrient transport and waste exchange between the dam and fetus, sustaining fetal growth. While the positive effects of 25-hydroxyvitamin D3 (25-OH-D3) on animal performance have been reported, its impact on placental function remains [...] Read more.
The placenta plays a crucial role in nutrient transport and waste exchange between the dam and fetus, sustaining fetal growth. While the positive effects of 25-hydroxyvitamin D3 (25-OH-D3) on animal performance have been reported, its impact on placental function remains largely unknown. Therefore, this study aimed to investigate the effects of supplementing 25-OH-D3 in the diet of primiparous sows on reproductive performance, antioxidant capacity, placental oxidative stress, nutrient transport, and inflammatory response during mid-to-late gestation. A total of 45 healthy Landrace × Yorkshire primiparous sows on day 60 of gestation were selected and randomly allocated to three treatment groups based on body weight and backfat thickness: the control group (corn-soybean meal basal diet), the VD3 group (basal diet + 2000 IU VD3), and the 25-OH-D3 group (basal diet + 50 μg/kg 25-OH-D3). The results demonstrated that supplementation with 25-OH-D3 in the diet enhanced sows’ average litter weight and birth weight during mid-to-late gestation. Additionally, plasma malondialdehyde (MDA) concentrations in sows significantly decreased in the VD3 and 25-OH-D3 groups (p < 0.05). Furthermore, lower gene expressions of placental HO-1, GPX2, IL-8, and IL-6 were found in the VD3 or 25-OH-D3 groups (p < 0.05 or p < 0.10), while higher gene expressions of GLUT1 and SNAT2 in the placenta of sows were observed in the VD3 and 25-OH-D3 groups, respectively (p < 0.05). These findings indicate that the supplementation of VD3 and 25-OH-D3 in the diet of sows can improve their plasma oxidative stress status, enhance placental antioxidant capacity and nutrient transport, and reduce placental inflammatory responses, with more pronounced improvements in sow performance observed in sows fed diets supplemented with 25-OH-D3. Full article
(This article belongs to the Special Issue Oxidative Stress in Reproduction of Mammals)
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<p>The effect of supplementing VD<sub>3</sub> and 25-OH-D<sub>3</sub> to the sow diet on the mRNA expression of placental antioxidant-related genes during mid-to-late gestation. The results are presented as mean ± SEM, n = 8. * represents a significant difference (<span class="html-italic">p</span> &lt; 0.05). CT = control group fed with the basal diet; VD<sub>3</sub> = VD<sub>3</sub> group fed with the supplementation of 2000 IU/kg Vitamin D<sub>3</sub> in the basal diet; 25-OH-D<sub>3</sub> = 25-OH-D<sub>3</sub> group fed with the supplementation of 50 µg/kg 25-OH-D<sub>3</sub> in the basal diet. HO-1 = heme oxygenase-1; Nrf2 = nuclear factor-erythroid 2-related factor 2; SOD1 = superoxide dismutase 1; SOD2 = superoxide dismutase 2; CAT = catalase; GPX1 = glutathione peroxidase 1; GPX2 = glutathione peroxidase 2.</p>
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<p>The effect of supplementing VD<sub>3</sub> and 25-OH-D<sub>3</sub> into the sow diet on the mRNA expression of placental nutrient transport (<b>a</b>) and immune-related genes (<b>b</b>) during mid-to-late gestation. The results are presented as mean ± SEM, <span class="html-italic">n</span> = 8. * represents a significant difference (<span class="html-italic">p</span> &lt; 0.05). CT = control group fed with the basal diet; VD<sub>3</sub> = VD<sub>3</sub> group fed with the supplementation of 2000 IU/kg Vitamin D<sub>3</sub> in the basal diet; 25-OH-D<sub>3</sub> = 25-OH-D<sub>3</sub> group fed with the supplementation of 50 µg/kg 25-OH-D<sub>3</sub> in the basal diet. <span class="html-italic">GLUT1</span> = glucose transporter type 1; <span class="html-italic">SNAT2</span> = sodium coupled neutral amino acid transporter 2; <span class="html-italic">SNAT1</span> = sodium coupled neutral amino acid transporter 1; <span class="html-italic">VEGFA</span> = vascular endothelial growth factor A; <span class="html-italic">IL-8</span> = interleukin-8; <span class="html-italic">IL-6</span> = interleukin-6; <span class="html-italic">IL-1β</span> = interleukin-1β; <span class="html-italic">TNF-α</span> = tumor necrosis factor-α.</p>
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