International Journal of Molecular Sciences

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15 pages, 6021 KiB

Open AccessArticle

Exploring the Importance of Differential Expression of Autophagy Markers in Term Placentas from Late-Onset Preeclamptic Pregnancies

by Luis M. Garcia-Puente, Cielo García-Montero, Oscar Fraile-Martinez, Julia Bujan, Juan A. De León-Luis, Coral Bravo, Patrocinio Rodríguez-Benitez, Laura López-González, Raul Díaz-Pedrero, Melchor Álvarez-Mon, Natalio García-Honduvilla, Miguel A. Saez and Miguel A. Ortega

Int. J. Mol. Sci. 2024, 25(4), 2029; https://doi.org/10.3390/ijms25042029 - 7 Feb 2024

Cited by 1 | Viewed by 782

Abstract

Preeclampsia (PE) is a serious hypertensive disorder affecting 4–5% of pregnancies globally, leading to maternal and perinatal morbidity and mortality and reducing life expectancy in surviving women post-gestation. Late-onset PE (LO-PE) is a clinical type of PE diagnosed after 34 weeks of gestation, [...] Read more.

Preeclampsia (PE) is a serious hypertensive disorder affecting 4–5% of pregnancies globally, leading to maternal and perinatal morbidity and mortality and reducing life expectancy in surviving women post-gestation. Late-onset PE (LO-PE) is a clinical type of PE diagnosed after 34 weeks of gestation, being less severe than the early-onset PE (EO-PE) variant, although both entities have a notable impact on the placenta. Despite the fact that most studies have focused on EO-PE, LO-PE does not deserve less attention since its prevalence is much higher and little is known about the role of the placenta in this pathology. Via RT-qPCR and immunohistochemistry methods, we measured the gene and protein expressions of several macroautophagy markers in the chorionic villi of placentas from women who underwent LO-PE (n = 68) and compared them to normal pregnancies (n = 43). We observed a markedly distinct expression pattern, noticing a significant drop in NUP62 expression and a considerable rise in the gene and protein expressions of ULK1, ATG9A, LC3, ATG5, STX-17, and LAMP-1 in the placentas of women with LO-PE. A major induction of autophagic processes was found in the placental tissue of patients with LO-PE. Abnormal signaling expression of these molecular patterns in this condition aids in the understanding of the complexity of pathophysiology and proposes biomarkers for the clinical management of these patients. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications)

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19 pages, 938 KiB

Open AccessArticle

Comparative Evaluation of Adipokine Metrics for the Diagnosis of Gestational Diabetes Mellitus

by Maciej Kamiński, Radzisław Mierzyński, Elżbieta Poniedziałek-Czajkowska, Agata Sadowska, Maciej Sotowski and Bożena Leszczyńska-Gorzelak

Int. J. Mol. Sci. 2024, 25(1), 175; https://doi.org/10.3390/ijms25010175 - 22 Dec 2023

Viewed by 788

Abstract

Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Adipokines, predominantly secreted by adipose tissue, are involved in numerous metabolic processes. The exact role of adipokines in the pathogenesis of GDM is still not well known, and numerous [...] Read more.

Gestational diabetes mellitus (GDM) is one of the most common medical disorders in pregnancy. Adipokines, predominantly secreted by adipose tissue, are involved in numerous metabolic processes. The exact role of adipokines in the pathogenesis of GDM is still not well known, and numerous adipokines have been analysed throughout pregnancy and proposed as biomarkers of GDM. This study aimed to evaluate serum adiponectin, chemerin, lipocalin and apelin levels in GDM and non-GDM women, to assess them as clinically useful biomarkers of the occurrence of GDM and to demonstrate the correlation between the levels of the above adipokines in the blood serum and the increased risk of the development of GDM. The role of these adipokines in the pathogenesis of GDM was also analysed. The statistically significant differences between the levels of adiponectin (7234.6 vs. 9837.5 ng/mL, p < 0.0001), chemerin (264.0 vs. 206.7 ng/mL, p < 0.0001) and lipocalin (39.5 vs. 19.4 ng/mL, p < 0.0001) were observed between pregnant women with GDM and healthy ones. The diagnostic usefulness of the tested adipokines in detecting GDM was also assessed. The research results confirm the hypothesis on the significance of adiponectin, chemerin, lipocalin and apelin in the pathophysiological mechanisms of GDM. We speculate that these adipokines could potentially be established as novel biomarkers for the prediction and early diagnosis of GDM. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications)

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15 pages, 4981 KiB

Open AccessArticle

The Influence of Nicotine on Trophoblast-Derived Exosomes in a Mouse Model of Pathogenic Preeclampsia

by Ayane Kubo, Keiichi Matsubara, Yuko Matsubara, Hirotomo Nakaoka and Takashi Sugiyama

Int. J. Mol. Sci. 2023, 24(13), 11126; https://doi.org/10.3390/ijms241311126 - 5 Jul 2023

Cited by 1 | Viewed by 1239

Abstract

Preeclampsia (PE) is a serious complication of pregnancy with a pathogenesis that is not fully understood, though it involves the impaired invasion of extravillous trophoblasts (EVTs) into the decidual layer during implantation. Because the risk of PE is actually decreased by cigarette smoking, [...] Read more.

Preeclampsia (PE) is a serious complication of pregnancy with a pathogenesis that is not fully understood, though it involves the impaired invasion of extravillous trophoblasts (EVTs) into the decidual layer during implantation. Because the risk of PE is actually decreased by cigarette smoking, we considered the possibility that nicotine, a critical component of tobacco smoke, might protect against PE by modifying the content of exosomes from EVTs. We investigated the effects of nicotine on our PE model mouse and evaluated blood pressure. Next, exosomes were extracted from nicotine-treated extravillous trophoblasts (HTR-8/SVneo), and the peptide samples were evaluated by DIA (Data Independent Acquisition) proteomic analysis following nano LC-MS/MS. Hub proteins were identified using bioinformatic analysis. We found that nicotine significantly reduced blood pressure in a PE mouse model. Furthermore, we identified many proteins whose abundance in exosomes was modified by nicotine treatment of EVTs, and we used bioinformatic annotation and network analysis to select five key hub proteins with potential roles in the pathogenesis or prevention of PE. EVT-derived exosomes might influence the pathogenesis of PE because the cargo delivered by exosomes can signal to and modify the receiving cells and their environment. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications)

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24 pages, 3835 KiB

Open AccessArticle

Introducing and Implementing Genetic Assessment in Cardio-Obstetrics Clinical Practice: Clinical and Genetic Workup of Patients with Cardiomyopathy

by Ghadeera Al Mansoori, Wael Al Mahmeed, Saleema Wani, Bashir Taha Salih, Tarek El Ansari, Fathima Farook, Zenab Farooq, Howaida Khair, Kornelia Zaręba, Nahid Al Dhahouri, Anjana Raj, Roger S. Foo, Bassam R. Ali, Fatma Al Jasmi and Nadia Akawi

Int. J. Mol. Sci. 2023, 24(11), 9119; https://doi.org/10.3390/ijms24119119 - 23 May 2023

Cited by 1 | Viewed by 1450

Abstract

Cardiovascular disease (CVD) during pregnancy varies significantly worldwide, influenced by factors such as access to healthcare, delayed diagnosis, causes, and risk factors. Our study sought to explore the spectrum of CVD present in pregnant women in the United Arab Emirates to better understand [...] Read more.

Cardiovascular disease (CVD) during pregnancy varies significantly worldwide, influenced by factors such as access to healthcare, delayed diagnosis, causes, and risk factors. Our study sought to explore the spectrum of CVD present in pregnant women in the United Arab Emirates to better understand this population’s unique needs and challenges. Central to our study is an emphasis on the importance of implementing a multidisciplinary approach that involves the collaboration of obstetricians, cardiologists, geneticists, and other healthcare professionals to ensure that patients receive comprehensive and coordinated care. This approach can also help identify high-risk patients and implement preventive measures to reduce the occurrence of adverse maternal outcomes. Furthermore, increasing awareness among women about the risk of CVD during pregnancy and obtaining detailed family histories can help in the early identification and management of these conditions. Genetic testing and family screening can also aid in identifying inherited CVD that can be passed down through families. To illustrate the significance of such an approach, we provide a comprehensive analysis of five women’s cases from our retrospective study of 800 women. The findings from our study emphasize the importance of addressing maternal cardiac health in pregnancy and the need for targeted interventions and improvements in the existing healthcare system to reduce adverse maternal outcomes. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications)

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18 pages, 5663 KiB

Open AccessArticle

Decidual Stromal Cell Ferroptosis Associated with Abnormal Iron Metabolism Is Implicated in the Pathogenesis of Recurrent Pregnancy Loss

by Fengrun Sun, Liyuan Cui, Jinfeng Qian, Mengdie Li, Lanting Chen, Chunqin Chen, Dajin Li, Songcun Wang and Meirong Du

Int. J. Mol. Sci. 2023, 24(9), 7836; https://doi.org/10.3390/ijms24097836 - 25 Apr 2023

Cited by 7 | Viewed by 2645

Abstract

Iron is necessary for various critical biological processes, but iron overload is also dangerous since labile iron is redox-active and toxic. We found that low serum iron and decidual local iron deposition existed simultaneously in recurrent pregnancy loss (RPL) patients. Mice fed with [...] Read more.

Iron is necessary for various critical biological processes, but iron overload is also dangerous since labile iron is redox-active and toxic. We found that low serum iron and decidual local iron deposition existed simultaneously in recurrent pregnancy loss (RPL) patients. Mice fed with a low-iron diet (LID) also showed iron deposition in the decidua and adverse pregnancy outcomes. Decreased ferroportin (cellular iron exporter) expression that inhibited the iron export from decidual stromal cells (DSCs) might be the reason for local iron deposition in DSCs from low-serum-iron RPL patients and LID-fed mice. Iron supplementation reduced iron deposition in the decidua of spontaneous abortion models and improved pregnancy outcomes. Local iron overload caused ferroptosis of DSCs by downregulating glutathione (GSH) and glutathione peroxidase 4 levels. Both GSH and cystine (for the synthesis of GSH) supplementation reduced iron-induced lipid reactive oxygen species (ROS) and cell death in DSCs. Ferroptosis inhibitor, cysteine, and GSH supplementation all effectively attenuated DSC ferroptosis and reversed embryo loss in the spontaneous abortion model and LPS-induced abortion model, making ferroptosis mitigation a potential therapeutic target for RPL patients. Further study that improves our understanding of low-serum-iron-induced DSC ferroptosis is needed to inform further clinical evaluations of the safety and efficacy of iron supplementation in women during pregnancy. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications)

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15 pages, 2987 KiB

Open AccessArticle

Membrane Lesions and Reduced Life Span of Red Blood Cells in Preeclampsia as Evidenced by Atomic Force Microscopy

by Ina Giosheva, Velichka Strijkova, Regina Komsa-Penkova, Sashka Krumova, Ariana Langari, Avgustina Danailova, Stefka G. Taneva, Tanya Stoyanova, Lora Topalova, Emil Gartchev, Galya Georgieva and Svetla Todinova

Int. J. Mol. Sci. 2023, 24(8), 7100; https://doi.org/10.3390/ijms24087100 - 12 Apr 2023

Cited by 2 | Viewed by 1557

Abstract

Preeclampsia (PE) presents with maternal de novo hypertension and significant proteinuria and is one of the leading causes of maternal and perinatal morbidity and mortality with unknown etiology. The disease is associated with inflammatory vascular response and severe red blood cell (RBC) morphology [...] Read more.

Preeclampsia (PE) presents with maternal de novo hypertension and significant proteinuria and is one of the leading causes of maternal and perinatal morbidity and mortality with unknown etiology. The disease is associated with inflammatory vascular response and severe red blood cell (RBC) morphology changes. This study examined the nanoscopic morphological changes of RBCs from PE women versus normotensive healthy pregnant controls (PCs) and non-pregnant controls (NPCs) applying atomic force microscopy (AFM) imaging. The results revealed that the membrane of fresh PE RBCs differed significantly from healthy ones by the presence of invaginations and protrusions and an increased roughness value (R_rms) (4.7 ± 0.8 nm for PE vs. 3.8 ± 0.5 nm and 2.9 ± 0.4 nm for PCs and NPCs, respectively). PE-cells aging resulted in more pronounced protrusions and concavities, with exponentially increasing R_rms values, in contrast to the controls, where the R_rms parameter decreased linearly with time. The R_rms, evaluated on a 2 × 2 µm² scanned area, for senescent PE cells (13 ± 2.0 nm) was significantly higher (p < 0.01) than that of PCs (1.5 ± 0.2 nm) and NPCs (1.9 ± 0.2 nm). Furthermore, the RBCs from PE patients appeared fragile, and often only ghosts were observed instead of intact cells at 20–30 days of aging. Oxidative-stress simulation on healthy cells led to RBC membrane features similar to those observed for PE cells. The results demonstrate that the most pronounced effects on RBCs in PE patients are related to impaired membrane homogeneity and strongly altered roughness values, as well as to vesiculation and ghost formation in the course of cell aging. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications)

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15 pages, 2835 KiB

Open AccessArticle

Tim-3 Coordinates Macrophage-Trophoblast Crosstalk via Angiogenic Growth Factors to Promote Pregnancy Maintenance

by Liyuan Cui, Fengrun Sun, Yuanyuan Xu, Mengdie Li, Lanting Chen, Chunqin Chen, Jinfeng Qian, Dajin Li, Meirong Du and Songcun Wang

Int. J. Mol. Sci. 2023, 24(2), 1538; https://doi.org/10.3390/ijms24021538 - 12 Jan 2023

Cited by 2 | Viewed by 1706

Abstract

T-cell immunoglobulin mucin-3 (Tim-3) is an important checkpoint that induces maternal–fetal tolerance in pregnancy. Macrophages (Mφs) play essential roles in maintaining maternal–fetal tolerance, remodeling spiral arteries, and regulating trophoblast biological behaviors. In the present study, the formation of the labyrinth zone showed striking [...] Read more.

T-cell immunoglobulin mucin-3 (Tim-3) is an important checkpoint that induces maternal–fetal tolerance in pregnancy. Macrophages (Mφs) play essential roles in maintaining maternal–fetal tolerance, remodeling spiral arteries, and regulating trophoblast biological behaviors. In the present study, the formation of the labyrinth zone showed striking defects in pregnant mice treated with Tim-3 neutralizing antibodies. The adoptive transfer of Tim-3⁺Mφs, rather than Tim-3⁻Mφs, reversed the murine placental dysplasia resulting from Mφ depletion. With the higher production of angiogenic growth factors (AGFs, including PDGF-AA, TGF-α, and VEGF), Tim-3⁺dMφs were more beneficial in promoting the invasion and tube formation ability of trophoblasts. The blockade of AGFs in Tim-3⁺Mφs led to the narrowing of the labyrinthine layer of the placenta, compromising maternal–fetal tolerance, and increasing the risk of fetal loss. Meanwhile, the AGFs-treated Tim-3⁻Mφs could resolve the placental dysplasia and fetal loss resulting from Mφ depletion. These findings emphasized the vital roles of Tim-3 in coordinating Mφs-extravillous trophoblasts interaction via AGFs to promote pregnancy maintenance and in extending the role of checkpoint signaling in placental development. The results obtained in our study also firmly demonstrated that careful consideration of reproductive safety should be taken when selecting immune checkpoint and AGF blockade therapies in real-world clinical care. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications)

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Review

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22 pages, 1837 KiB

Open AccessReview

Excessive Pregestational Weight and Maternal Obstetric Complications: The Role of Adipokines

by Jorge Valencia-Ortega, Juan Mario Solis-Paredes, Renata Saucedo, Guadalupe Estrada-Gutierrez and Ignacio Camacho-Arroyo

Int. J. Mol. Sci. 2023, 24(19), 14678; https://doi.org/10.3390/ijms241914678 - 28 Sep 2023

Viewed by 1048

Abstract

There is a high frequency of overweight and obesity in women of reproductive age. Women who start pregnancy with overweight or obesity have an increased risk of developing maternal obstetric complications such as gestational hypertension, pre-eclampsia, gestational diabetes mellitus, postpartum hemorrhage, and requiring [...] Read more.

There is a high frequency of overweight and obesity in women of reproductive age. Women who start pregnancy with overweight or obesity have an increased risk of developing maternal obstetric complications such as gestational hypertension, pre-eclampsia, gestational diabetes mellitus, postpartum hemorrhage, and requiring C-section to resolve the pregnancy with a higher risk of C-section surgical site infection. Excessive weight in pregnancy is characterized by dysregulation of adipokines, the functions of which partly explain the predisposition of pregnant women with overweight or obesity to these maternal obstetric complications. This review compiles, organizes, and analyzes the most recent studies on adipokines in pregnant women with excess weight and the potential pathophysiological mechanisms favoring the development of maternal pregnancy complications. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications)

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