International Journal of Molecular Sciences

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5 pages, 180 KiB

Open AccessEditorial

Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child

by Joško Osredkar

Int. J. Mol. Sci. 2023, 24(6), 5958; https://doi.org/10.3390/ijms24065958 - 22 Mar 2023

Cited by 1 | Viewed by 952

Abstract

In all living organisms, there is a delicate balance between oxidation caused by reactive species (RS, also called free radicals) and antioxidant defence [...] Full article

(This article belongs to the Special Issue Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child)

Research

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14 pages, 1095 KiB

Open AccessArticle

Altered Thermal Behavior of Blood Plasma Proteome Related to Inflammatory Cytokines in Early Pregnancy Loss

by Regina Komsa-Penkova, Avgustina Danailova, Sashka Krumova, Galya Georgieva, Ina Giosheva, Lidia Gartcheva, Ivan Iliev, Emil Gartchev, Kameliya Kercheva, Alexey Savov and Svetla Todinova

Int. J. Mol. Sci. 2022, 23(15), 8764; https://doi.org/10.3390/ijms23158764 - 6 Aug 2022

Cited by 5 | Viewed by 1827

Abstract

Early pregnancy loss (EPL) is a relatively common pathology of which almost 50% of cases remain idiopathic. In the search for novel biomarkers, differential scanning calorimetry (DSC) is intensively used to characterize the thermodynamic behavior of blood plasma/serum proteome in health and disease. [...] Read more.

Early pregnancy loss (EPL) is a relatively common pathology of which almost 50% of cases remain idiopathic. In the search for novel biomarkers, differential scanning calorimetry (DSC) is intensively used to characterize the thermodynamic behavior of blood plasma/serum proteome in health and disease. Herein, for the first time, we investigate the DSC denaturation profiles of blood plasma derived from patients suffering EPL compared to healthy pregnant and non-pregnant women. Data analysis reveals that 58% of the EPL thermograms differ significantly from those of healthy pregnant women. Thermal stabilization of a fraction of albumin-assigned transition with concomitant suppression of the major and enhancement of the globulin-assigned transition are characteristic features of EPL calorimetric profiles that could be used as a new indicator of a risk pregnancy. The presented results suggest an altered composition or intermolecular interactions of the plasma proteome of women with EPL. In addition, the alterations of the EPL thermograms correlate with the increased blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and a higher prevalence of the polymorphism in the plasminogen activator inhibitor type-1 (PAI-1) gene, suggesting an expression of an overall enhanced immune response. The concomitant changes in plasma thermograms confirm the potential of the DSC approach for distinguishing changes in the pathological state of the blood plasma proteome. Full article

(This article belongs to the Special Issue Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child)

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15 pages, 2667 KiB

Open AccessArticle

Gamma Secretase Inhibitors as Potential Therapeutic Targets for Notch Signaling in Uterine Leiomyosarcoma

by Yasmin Abedin, Sofia Gabrilovich, Emily Alpert, Erica Rego, Salma Begum, Qingshi Zhao, Debra Heller, Mark H. Einstein and Nataki C. Douglas

Int. J. Mol. Sci. 2022, 23(11), 5980; https://doi.org/10.3390/ijms23115980 - 26 May 2022

Cited by 4 | Viewed by 2464

Abstract

Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer with few effective therapeutics. The Notch signaling pathway is evolutionarily conserved with oncogenic properties, but it has not been well studied in uLMS. The purpose of our study was to determine expression of Notch [...] Read more.

Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer with few effective therapeutics. The Notch signaling pathway is evolutionarily conserved with oncogenic properties, but it has not been well studied in uLMS. The purpose of our study was to determine expression of Notch family genes and proteins and to investigate the therapeutic effect of γ-secretase inhibitors (GSIs), indirect inhibitors of Notch signaling, in uLMS. We determined expression of Notch genes and proteins in benign uterine smooth muscle tissue, fibroids, and uLMS samples by immunostaining and in two uLMS cell lines, SK-UT-1B (uterine primary) and SK-LMS-1 (vulvar metastasis) by RT-PCR, Western blot and immunostaining. We exposed our cell lines to GSIs, DAPT and MK-0752, and measured expression of HES1, a downstream effector of Notch. Notch proteins were differentially expressed in uLMS. Expression of NOTCH3 and NOTCH4 was higher in uLMS samples than in benign uterine smooth muscle and fibroids. Expression of NOTCH4 was higher in SK-LMS-1 compared to SK-UT-1B. Exposure of SK-UT-1B and SK-LMS-1 to DAPT and MK-0752 decreased expression of HES1 and decreased uLMS cell viability in a dose- and time-dependent manner that was unique to each GSI. Our findings suggest that GSIs are potential therapeutics for uLMS, albeit with limited efficacy. Full article

(This article belongs to the Special Issue Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child)

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15 pages, 2500 KiB

Open AccessArticle

Dysregulation of Oxygen Sensing/Response Pathways in Pregnancies Complicated by Idiopathic Intrauterine Growth Restriction and Early-Onset Preeclampsia

by Sharon A. McCracken, Sean K. M. Seeho, Tamara Carrodus, Jenny H. Park, Narelle Woodland, Eileen D. M. Gallery, Jonathan M. Morris and Anthony W. Ashton

Int. J. Mol. Sci. 2022, 23(5), 2772; https://doi.org/10.3390/ijms23052772 - 2 Mar 2022

Cited by 6 | Viewed by 2370

Abstract

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are the leading causes of maternal and fetal morbidity/mortality. The central deficit in both conditions is impaired placentation due to poor trophoblast invasion, resulting in a hypoxic milieu in which oxidative stress contributes to the pathology. [...] Read more.

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are the leading causes of maternal and fetal morbidity/mortality. The central deficit in both conditions is impaired placentation due to poor trophoblast invasion, resulting in a hypoxic milieu in which oxidative stress contributes to the pathology. We examine the factors driving the hypoxic response in severely preterm PE (n = 19) and IUGR (n = 16) placentae compared to the spontaneous preterm (SPT) controls (n = 13) using immunoblotting, RT-PCR, immunohistochemistry, proximity ligation assays, and Co-IP. Both hypoxia-inducible factor (HIF)-1α and HIF-2α are increased at the protein level and functional in pathological placentae, as target genes prolyl hydroxylase domain (PHD)2, PHD3, and soluble fms-like tyrosine kinase-1 (sFlt-1) are increased. Accumulation of HIF-α-subunits occurs in the presence of accessory molecules required for their degradation (PHD1, PHD2, and PHD3 and the E3 ligase von Hippel–Lindau (VHL)), which were equally expressed or elevated in the placental lysates of PE and IUGR. However, complex formation between VHL and HIF-α-subunits is defective. This is associated with enhanced VHL/DJ1 complex formation in both PE and IUGR. In conclusion, we establish a significant mechanism driving the maladaptive responses to hypoxia in the placentae from severe PE and IUGR, which is central to the pathogenesis of both diseases. Full article

(This article belongs to the Special Issue Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child)

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12 pages, 1313 KiB

Open AccessArticle

Intrauterine Nitric Oxide Deficiency Weakens Differentiation of Vascular Smooth Muscle in Newborn Rats

by Anastasia A. Shvetsova, Anna A. Borzykh, Ekaterina K. Selivanova, Oxana O. Kiryukhina, Dina K. Gaynullina and Olga S. Tarasova

Int. J. Mol. Sci. 2021, 22(15), 8003; https://doi.org/10.3390/ijms22158003 - 27 Jul 2021

Cited by 4 | Viewed by 1795

Abstract

Nitric oxide (NO) deficiency during pregnancy is a key reason for preeclampsia development. Besides its important vasomotor role, NO is shown to regulate the cell transcriptome. However, the role of NO in transcriptional regulation of developing smooth muscle has never been studied before. [...] Read more.

Nitric oxide (NO) deficiency during pregnancy is a key reason for preeclampsia development. Besides its important vasomotor role, NO is shown to regulate the cell transcriptome. However, the role of NO in transcriptional regulation of developing smooth muscle has never been studied before. We hypothesized that in early ontogeny, NO is important for the regulation of arterial smooth muscle-specific genes expression. Pregnant rats consumed NO-synthase inhibitor L-NAME (500 mg/L in drinking water) from gestational day 10 till delivery, which led to an increase in blood pressure, a key manifestation of preeclampsia. L-NAME reduced blood concentrations of NO metabolites in dams and their newborn pups, as well as relaxations of pup aortic rings to acetylcholine. Using qPCR, we demonstrated reduced abundances of the smooth muscle-specific myosin heavy chain isoform, α-actin, SM22α, and L-type Ca²⁺-channel mRNAs in the aorta of newborn pups from the L-NAME group compared to control pups. To conclude, the intrauterine NO deficiency weakens gene expression specific for a contractile phenotype of arterial smooth muscle in newborn offspring. Full article

(This article belongs to the Special Issue Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child)

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Review

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9 pages, 1041 KiB

Open AccessReview

Oxidative Stress as a Potential Underlying Cause of Minimal and Mild Endometriosis-Related Infertility

by Gabija Didziokaite, Gabija Biliute, Jogaile Gudaite and Violeta Kvedariene

Int. J. Mol. Sci. 2023, 24(4), 3809; https://doi.org/10.3390/ijms24043809 - 14 Feb 2023

Cited by 8 | Viewed by 3872

Abstract

Oxidative stress (OS) plays an important role in a variety of physiological and pathological processes of the female reproductive system. In recent years the relationship between OS and endometriosis has been of particular interest, and a theory has been suggested that OS may [...] Read more.

Oxidative stress (OS) plays an important role in a variety of physiological and pathological processes of the female reproductive system. In recent years the relationship between OS and endometriosis has been of particular interest, and a theory has been suggested that OS may be a cause of endometriosis development. While the link between endometriosis and infertility is well established, minimal or mild stages of endometriosis are not considered to cause infertility. Increasing evidence of OS as a leading agent in the development of endometriosis has brought up a theory of minimal/mild endometriosis itself being one of the manifestations of high OS rather than a separate disease which directly causes infertility. Moreover, further development of the disease is thought to contribute to an increased production of reactive oxygen species (ROS) thus leading to the progression of endometriosis itself as well as to other pathological processes in the female reproductive system. Therefore, in case of minimal or mild endometriosis, the less invasive treatment could be offered in order to stop the ongoing cycle of endometriosis-reinforced excess ROS production and to reduce their harmful effects. In this article the existing connection between OS, endometriosis, and infertility is explored. Full article

(This article belongs to the Special Issue Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child)

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14 pages, 1135 KiB

Open AccessReview

The Significance of COVID-19 Diseases in Lipid Metabolism Pregnancy Women and Newborns

by Miljana Z. Jovandaric, Milan Dokic, Ivana R. Babovic, Srboljub Milicevic, Jelena Dotlic, Branislav Milosevic, Miljan Culjic, Luka Andric, Nemanja Dimic, Olga Mitrovic, Aleksandra Beleslin, Jovana Nikolic, Zorica Jestrovic and Sandra Babic

Int. J. Mol. Sci. 2022, 23(23), 15098; https://doi.org/10.3390/ijms232315098 - 1 Dec 2022

Cited by 5 | Viewed by 2232

Abstract

Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2. Elderly people, people with immunodeficiency, autoimmune and malignant diseases, as well as people with chronic diseases have a higher risk of developing more severe forms of the disease. Pregnant women and children can [...] Read more.

Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2. Elderly people, people with immunodeficiency, autoimmune and malignant diseases, as well as people with chronic diseases have a higher risk of developing more severe forms of the disease. Pregnant women and children can becomesick, although more often they are only the carriers of the virus. Recent studies have indicated that infants can also be infected by SARS-CoV-2 and develop a severe form of the disease with a fatal outcome. Acute Respiratory Distress Syndrome (ARDS) ina pregnant woman can affect the supply of oxygen to the fetus and initiate the mechanism of metabolic disorders of the fetus and newborn caused by asphyxia. The initial metabolic response of the newborn to the lack of oxygen in the tissues is the activation of anaerobic glycolysis in the tissues and an increase in the concentration of lactate and ketones. Lipid peroxidation, especially in nerve cells, is catalyzed by iron released from hemoglobin, transferrin and ferritin, whose release is induced by tissue acidosis and free oxygen radicals. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through various pathways, resulting in a decrease in the antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in the cells, ultimately leading to oxidative cell stress, and finally, death. Conclusion: damage to the mitochondria as a result of lipid peroxidation caused by the COVID-19 disease can cause the death of a newborn and pregnant women as well as short time and long-time sequelae. Full article

(This article belongs to the Special Issue Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child)

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23 pages, 695 KiB

Open AccessReview

Maternal Distress during Pregnancy and the Postpartum Period: Underlying Mechanisms and Child’s Developmental Outcomes—A Narrative Review

by Ljiljana Jeličić, Aleksandra Veselinović, Milica Ćirović, Vladimir Jakovljević, Saša Raičević and Miško Subotić

Int. J. Mol. Sci. 2022, 23(22), 13932; https://doi.org/10.3390/ijms232213932 - 11 Nov 2022

Cited by 9 | Viewed by 5695

Abstract

Maternal mental health may be considered a determining factor influencing fetal and child development. An essential factor with potentially negative consequences for a child’s psychophysiological development is the presence of maternal distress during pregnancy and the postpartum period. The review is organized and [...] Read more.

Maternal mental health may be considered a determining factor influencing fetal and child development. An essential factor with potentially negative consequences for a child’s psychophysiological development is the presence of maternal distress during pregnancy and the postpartum period. The review is organized and presented to explore and describe the effects of anxiety, stress, and depression in pregnancy and the postpartum period on adverse child developmental outcomes. The neurobiology of maternal distress and the transmission mechanisms at the molecular level to the fetus and child are noted. In addition, the paper discusses the findings of longitudinal studies in which early child development is monitored concerning the presence of maternal distress in pregnancy and the postpartum period. This topic gained importance in the COVID-19 pandemic context, during which a higher frequency of maternal psychological disorders was observed. The need for further interdisciplinary research on the relationship between maternal mental health and fetal/child development was highlighted, especially on the biological mechanisms underlying the transmission of maternal distress to the (unborn) child, to achieve positive developmental outcomes and improve maternal and child well-being. Full article

(This article belongs to the Special Issue Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child)

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14 pages, 697 KiB

Open AccessReview

Impact of Oxidative Stress on Molecular Mechanisms of Cervical Ripening in Pregnant Women

by Maciej W. Socha, Wojciech Flis, Mateusz Wartęga and Martyna Stankiewicz

Int. J. Mol. Sci. 2022, 23(21), 12780; https://doi.org/10.3390/ijms232112780 - 24 Oct 2022

Cited by 6 | Viewed by 2043

Abstract

Uterine cervix is one of the essential factors in labor and maintaining the proper course of pregnancy. During the last days of gestation, the cervix undergoes extensive changes manifested by transformation from a tight and rigid to one that is soft and able [...] Read more.

Uterine cervix is one of the essential factors in labor and maintaining the proper course of pregnancy. During the last days of gestation, the cervix undergoes extensive changes manifested by transformation from a tight and rigid to one that is soft and able to dilate. These changes can be summarized as “cervical ripening”. Changes in the cervical tissue can be referred to as remodeling of the extracellular matrix. The entire process is the result of a close relationship between biochemical and molecular pathways, which is strictly controlled by inflammatory and endocrine factors. When the production of reactive oxygen species exceeds the antioxidant capacity, oxidative stress occurs. A physiologic increase of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is observed through pregnancy. ROS play important roles as second messengers in many intracellular signaling cascades contributing to the course of gestation. This review considers their involvement in the cervical ripening process, emphasizing the molecular and biochemical pathways and the clinical implications. Full article

(This article belongs to the Special Issue Impact of Endogenic and Exogenic Oxidative Stress Triggers on Pregnant Woman, Fetus, and Child)

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