Role of Oxidative Stress and Inflammation in Maternal-Perinatal Well-Being

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 45384

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Pathological Anatomy Service, Central University Hospital of Defence-UAH Madrid, 28801 Alcala de Henares, Spain
Interests: placenta; histology; pathology
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Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
Interests: personalized medicine; clinical medicine; new therapies; medical–patient relationship
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Guest Editor
1. Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain
2. Department of Obstetrics and Gynecology, University Hospital Gregorio Marañón, 28009 Madrid, Spain
3. Health Research Institute Gregorio Marañón, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28009 Madrid, Spain
4. Maternal and Infant Research Investigation Unit, Alonso Family Foundation (UDIMIFFA), 28009 Madrid, Spain
Interests: pregnancy; maternal–perinatal well-being
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E-Mail Website
Guest Editor
1. Department of Public and Maternal and Child Health, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain. 2. Department of Obstetrics and Gynecology, University Hospital Gregorio Marañón, 28009 Madrid, Spain. 3. Health Research Institute Gregorio Marañón, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28009 Madrid, Spain. 4. Maternal and Infant Research Investigation Unit, Alonso Family Foundation (UDIMIFFA), 28009 Madrid, Spain.
Interests: pregnancy; maternal–perinatal well-being
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Guest Editor

E-Mail Website
Guest Editor
1. Department of Medicine and Medical Specialities, IRYCYS, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
2. Immune System Diseases-Rheumatology and Internal Medicine Service, University Hospital Príncipe de Asturias, (CIBEREHD), 28806 Alcala de Henares, Spain
Interests: immune system; systemic diseases; semiology; cytokines; translational medicine
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Special Issue Information

Dear Colleagues,

Maternal–fetal well-being depends on the proper integration and function of many physiological events and tissue structures during and after pregnancy. The human placenta is a tissue structure that can be affected by many situations throughout pregnancy. In this sense, the human placenta’s multiple mechanisms for adapting to all the different situations that affect maternal–fetal well-being are notable. One of the processes that most affects tissue structures is oxidative stress and inflammation. Therefore, the structures involved in maternal–fetal well-being must be studied in order to have a comprehensive view of the repercussions of the different pathologies and events that can modify maternal–fetal well-being.

Dr. Miguel Ortega
Dr. Miguel A. Saez
Dr. Miguel Ángel Alvarez de Mon
Prof. Dr. Coral Bravo
Prof. Dr. Julia Bujan
Prof. Dr. Juan Antonio De León-Luis
Prof. Dr. Natalio García-Honduvilla
Prof. Dr. Melchor Álvarez de Mon
Guest Editors

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Keywords

  • maternal–fetal well-being
  • placenta
  • umbilical cord
  • oxidative stress
  • inflammation
  • immune system
  • psychoneuroendocrinology
  • psychological stress
  • complications in maternal–fetal well-being

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Published Papers (15 papers)

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Research

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15 pages, 6566 KiB  
Article
Vitamin B12 Supplementation Improves Oocyte Development by Modulating Mitochondria and Yolk Protein in a Caffeine-Ingested Caenorhabditis elegans Model
by Hyemin Min, Mijin Lee, Sangwon Kang and Yhong-Hee Shim
Antioxidants 2024, 13(1), 53; https://doi.org/10.3390/antiox13010053 - 28 Dec 2023
Cited by 3 | Viewed by 1841
Abstract
Vitamin B12 is an essential cofactor involved in the function of two enzymes: cytosolic methionine synthase and mitochondrial methylmalonic-CoA mutase. In our previous studies, caffeine (1,3,7-trimethylxanthine), the most popular bioactivator, was shown to reduce yolk protein (vitellogenin) and fertility in a Caenorhabditis elegans [...] Read more.
Vitamin B12 is an essential cofactor involved in the function of two enzymes: cytosolic methionine synthase and mitochondrial methylmalonic-CoA mutase. In our previous studies, caffeine (1,3,7-trimethylxanthine), the most popular bioactivator, was shown to reduce yolk protein (vitellogenin) and fertility in a Caenorhabditis elegans model. Based on the previous finding that methionine supplementation increases vitellogenesis in C. elegans, we investigated the role of vitamin B12 in methionine-mediated vitellogenesis during oogenesis in caffeine-ingested animals (CIA). Vitamin B12 supplementation improved vitellogenesis and reduced oxidative stress by decreasing mitochondrial function in CIA. Furthermore, the decreased number of developing oocytes and high levels of reactive oxygen species in oocytes from CIA were recovered with vitamin B12 supplementation through a reduction in mitochondrial stress, which increased vitellogenesis. Taken together, vitamin B12 supplementation can reverse the negative effects of caffeine intake by enhancing methionine-mediated vitellogenesis and oocyte development by reducing mitochondrial stress. Full article
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12 pages, 496 KiB  
Article
Changes in Oxidative Stress and Intestinal Permeability during Pregnancy in Women with Gestational Diabetes Mellitus Treated with Metformin or Insulin and Healthy Controls: A Randomized Controlled Trial
by Andrea Fernández-Valero, Nerea Peña-Montero, Fuensanta Lima-Rubio, Carolina Gutiérrez-Repiso, Teresa María Linares-Pineda, María José Picón-César, Raquel Sancho-Marín, Francisco J. Tinahones, Sonsoles Morcillo and María Molina-Vega
Antioxidants 2023, 12(11), 1981; https://doi.org/10.3390/antiox12111981 - 8 Nov 2023
Cited by 1 | Viewed by 1378
Abstract
Both oxidative stress and intestinal permeability are increased in hyperglycemic situations and have been shown to be reduced by metformin in type 2 diabetes mellitus (T2DM) patients. The aim of this study was to elucidate the effect of metformin on oxidative stress and [...] Read more.
Both oxidative stress and intestinal permeability are increased in hyperglycemic situations and have been shown to be reduced by metformin in type 2 diabetes mellitus (T2DM) patients. The aim of this study was to elucidate the effect of metformin on oxidative stress and intestinal permeability in women with gestational diabetes mellitus (GDM) treated with metformin compared to those treated with insulin and healthy controls. A total of 120 women were included from August 2016 to February 2022: 41 received metformin (MET group), 38 received insulin (INS group), and 41 were healthy controls. Baseline and antenatal visits were carried out at 25.4 ± 4.8 and 36.1 ± 0.8 weeks of pregnancy, respectively. Advanced oxidation protein products (AOPPs), total antioxidant capacity (TAC), and zonulin levels were measured at every visit. Zonulin levels from baseline to prepartum visit increased significantly in both healthy controls (0.6 ± 0.9 to 1.2 ± 1.7 ng/mL, p = 0.004) and the INS group (0.4 ± 0.3 to 0.6 ± 0.5 ng/mL, p = 0.034) but did not significantly change in the MET group (0.4 ± 0.4 to 0.5 ± 0.4 ng/mL, p = 0.202). However, TAC and AOPP levels significantly increased in women with GDM, both in the INS and MET groups but not in the healthy controls. In conclusion, in our population, metformin has been shown to avoid an increase in intestinal permeability but failed to avoid an increase in oxidative stress related to hyperglycemia. Full article
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12 pages, 288 KiB  
Article
Evaluation of Vitamin E Isoforms in Placental Tissue and Their Relationship with Maternal Dietary Intake and Plasma Concentrations in Mother–Infant Dyads
by Ishani Jhamb, Alyssa Freeman, Michelle R. Lotfi, Matthew VanOrmer, Corrine Hanson, Ann Anderson-Berry and Melissa Thoene
Antioxidants 2023, 12(10), 1797; https://doi.org/10.3390/antiox12101797 - 24 Sep 2023
Viewed by 1195
Abstract
α-tocopherol is a vitamin E isoform with potent antioxidant activity, while the γ-tocopherol isoform of vitamin E exerts more pro-inflammatory effects. In maternal–fetal environments, increased plasma α-tocopherol concentrations are associated with positive birth outcomes, while higher γ-tocopherol concentrations are linked with negative pregnancy [...] Read more.
α-tocopherol is a vitamin E isoform with potent antioxidant activity, while the γ-tocopherol isoform of vitamin E exerts more pro-inflammatory effects. In maternal–fetal environments, increased plasma α-tocopherol concentrations are associated with positive birth outcomes, while higher γ-tocopherol concentrations are linked with negative pregnancy outcomes. However, little is known about tocopherol concentrations in placental tissue and their role in modulating placental oxidative stress, a process that is implicated in many complications of pregnancy. The objectives of this research are to evaluate the concentrations of α- and γ-tocopherol in placental tissue and assess relationships with maternal and umbilical cord plasma concentrations. A total of 82 mother–infant dyads were enrolled at the time of delivery, and maternal and umbilical cord blood samples and placenta samples were collected. α- and γ-tocopherol concentrations in these samples were analyzed by high-performance liquid chromatography (HPLC). γ-tocopherol concentrations demonstrated significant, positive correlations among all sample types (p-values < 0.001). Placental tissue had a significantly lower ratio of α:γ-tocopherol concentrations when compared to maternal plasma and umbilical cord plasma (2.9 vs. 9.9 vs. 13.2, respectively; p < 0.001). Additional research should explore possible mechanisms for tocopherol storage and transfer in placental tissue and assess relationships between placental tocopherol concentrations and measures of maternal–fetal oxidative stress and clinical outcomes of pregnancy. Full article
10 pages, 1525 KiB  
Communication
Effect of SARS-CoV-2 Infection and COVID-19 Vaccination on Oxidative Status of Human Placenta: A Preliminary Study
by Kristína Macáková, Petra Pšenková, Nadja Šupčíková, Barbora Vlková, Peter Celec and Jozef Záhumenský
Antioxidants 2023, 12(7), 1403; https://doi.org/10.3390/antiox12071403 - 9 Jul 2023
Viewed by 2570
Abstract
Infection with SARS-CoV-2 during pregnancy increases the risk of pregnancy complications associated with inflammation, which could lead to oxidative stress in the placenta. Whether vaccination against COVID-19 has any effect is unclear. This study aimed to analyze the effects of SARS-CoV-2 infection and [...] Read more.
Infection with SARS-CoV-2 during pregnancy increases the risk of pregnancy complications associated with inflammation, which could lead to oxidative stress in the placenta. Whether vaccination against COVID-19 has any effect is unclear. This study aimed to analyze the effects of SARS-CoV-2 infection and vaccination against COVID-19 during pregnancy on oxidative stress in the placenta and on extracellular DNA (ecDNA) in umbilical cord plasma. Placenta samples from healthy uninfected and unvaccinated control patients who recovered from COVID-19 and women vaccinated against COVID-19 during pregnancy were collected. Biomarkers of oxidative damage and antioxidant capacity were assessed in the placenta homogenates. EcDNA and deoxyribonuclease activity were quantified in umbilical cord plasma using real-time PCR and the single radial enzyme diffusion method, respectively. Markers of oxidative damage to lipids and proteins as well as antioxidant capacity in the placenta did not differ between the study groups. No differences were observed in total, nuclear or mitochondrial ecDNA, or deoxyribonuclease activity in the umbilical cord plasma. Taking into account the limits of a small observational study, our results suggest that the infection with SARS-CoV-2 and vaccination against COVID-19 do not induce any major disturbances in the balance between the production of free radicals and antioxidant activity in the placenta. This is in line with the minor effects on fetal outcomes and ecDNA as a suggested marker of fetal well-being. Full article
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16 pages, 1688 KiB  
Article
Maternal and Neonatal Factors Modulating Breast Milk Cytokines in the First Month of Lactation
by David Ramiro-Cortijo, Gloria Herranz Carrillo, Pratibha Singh, Miguel Rebollo-Hernanz, Pilar Rodríguez-Rodríguez, Santiago Ruvira, María Martín-Trueba, Camilia R. Martin and Silvia M. Arribas
Antioxidants 2023, 12(5), 996; https://doi.org/10.3390/antiox12050996 - 25 Apr 2023
Cited by 5 | Viewed by 2696
Abstract
Breast milk (BM) cytokines support and modulate infant immunity, being particularly relevant in premature neonates with adverse outcomes (NAO). This study aimed to examine, in a cohort of Spanish breastfeeding women, changes in BM cytokines in the first month of lactation, their modulation [...] Read more.
Breast milk (BM) cytokines support and modulate infant immunity, being particularly relevant in premature neonates with adverse outcomes (NAO). This study aimed to examine, in a cohort of Spanish breastfeeding women, changes in BM cytokines in the first month of lactation, their modulation by neonatal factors (sex, gestational age, and NAO), maternal factors (obstetric complications, C-section, and diet), and their relationship with oxidative status. Sixty-three mother-neonate dyads were studied at days 7 and 28 of lactation. Dietary habits were assessed by a 72-h dietary recall, and the maternal dietary inflammatory index (mDII) was calculated. BM cytokines (IL-10, IL-13, IL-8, MCP-1, and TNFα) were assessed by ultra-sensitive chemiluminescence. Total antioxidant capacity was assessed by the ABTS method and lipid peroxidation by the MDA+HNE kit. From days 7 to 28 of lactation, the levels of IL-10 and TNFα remained stable, while IL-13 increased (β = 0.85 ± 0.12, p < 0.001) and IL-8 and MCP-1 levels decreased (β = −0.64 ± 0.27, p = 0.019; β = −0.98 ± 0.22, p < 0.001; respectively). Antioxidant capacity and lipid peroxidation also decrease during lactation. Neonatal sex did not influence any of the cytokines, but BM from mothers with male infants had a higher antioxidant capacity. Gestational age was associated with male sex and NAO, being inversely correlated with the BM proinflammatory cytokines IL-8, MCP-1, and TNFα. From days 7 to 28 of lactation, BM from women with NAO infants increased MCP-1 levels and had a larger drop in antioxidant capacity, with the opposite trend in lipid peroxidation. MCP-1 was also significantly higher in women undergoing C-section; this cytokine declined in women who decreased mDII during lactation, while IL-10 increased. Linear mixed regression models evidenced that the most important factors modulating BM cytokines were lactation period and gestational age. In conclusion, during the first month of lactation, BM cytokines shift towards an anti-inflammatory profile, influenced mainly by prematurity. BM MCP-1 is associated with maternal and neonatal inflammatory processes. Full article
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19 pages, 2303 KiB  
Article
Preeclampsia Affects Lipid Metabolism and HDL Function in Mothers and Their Offspring
by Julia T. Stadler, Hubert Scharnagl, Christian Wadsack and Gunther Marsche
Antioxidants 2023, 12(4), 795; https://doi.org/10.3390/antiox12040795 - 24 Mar 2023
Cited by 9 | Viewed by 2952
Abstract
Preeclampsia (PE) is linked to an overall increased cardiovascular risk for both the mother and child. Functional impairment of high-density lipoproteins (HDL) may contribute to the excess cardiovascular risk associated with PE. In this study, we investigated the effects of PE on maternal [...] Read more.
Preeclampsia (PE) is linked to an overall increased cardiovascular risk for both the mother and child. Functional impairment of high-density lipoproteins (HDL) may contribute to the excess cardiovascular risk associated with PE. In this study, we investigated the effects of PE on maternal and neonatal lipid metabolism, and the parameters of HDL composition and function. The study cohort included 32 normotensive pregnant women, 18 women diagnosed with early-onset PE, and 14 women with late-onset PE. In mothers, early- and late-onset PE was associated with atherogenic dyslipidemia, characterized by high plasma triglycerides and low HDL-cholesterol levels. We observed a shift from large HDL to smaller HDL subclasses in early-onset PE, which was associated with an increased plasma antioxidant capacity in mothers. PE was further associated with markedly increased levels of HDL-associated apolipoprotein (apo) C-II in mothers, and linked to the triglyceride content of HDL. In neonates of early-onset PE, total cholesterol levels were increased, whereas HDL cholesterol efflux capacity was markedly reduced in neonates from late-onset PE. In conclusion, early- and late-onset PE profoundly affect maternal lipid metabolism, potentially contributing to disease manifestation and increased cardiovascular risk later in life. PE is also associated with changes in neonatal HDL composition and function, demonstrating that complications of pregnancy affect neonatal lipoprotein metabolism. Full article
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23 pages, 11235 KiB  
Article
Monosodium Glutamate Perturbs Human Trophoblast Invasion and Differentiation through a Reactive Oxygen Species-Mediated Pathway: An In-Vitro Assessment
by Indrani Mukherjee, Subhrajit Biswas, Sunil Singh, Joyeeta Talukdar, Mohammed S. Alqahtani, Mohamed Abbas, Tapas Chandra Nag, Asit Ranjan Mridha, Surabhi Gupta, Jai Bhagwan Sharma, Supriya Kumari, Ruby Dhar and Subhradip Karmakar
Antioxidants 2023, 12(3), 634; https://doi.org/10.3390/antiox12030634 - 3 Mar 2023
Cited by 2 | Viewed by 2122
Abstract
The overproduction of reactive oxygen species (ROS) has been associated with various human diseases. ROS exert a multitude of biological effects with both physiological and pathological consequences. Monosodium glutamate (MSG), a sodium salt of the natural amino acid glutamate, is a flavor-enhancing food [...] Read more.
The overproduction of reactive oxygen species (ROS) has been associated with various human diseases. ROS exert a multitude of biological effects with both physiological and pathological consequences. Monosodium glutamate (MSG), a sodium salt of the natural amino acid glutamate, is a flavor-enhancing food additive, which is widely used in Asian cuisine and is an ingredient that brings out the “umami” meat flavor. MSG consumption in rats is associated with ROS generation. Owing to its consumption as part of the fast-food culture and concerns about its possible effects on pregnancy, we aimed to study the impact of MSG on placental trophoblast cells. MSG exposure influenced trophoblast invasion and differentiation, two of the most critical functions during placentation through enhanced production of ROS. Similar findings were also observed on MSG-treated placental explants, as confirmed by elevated Nrf2 levels. Ultrastructural studies revealed signs of subcellular injury by MSG exposure. Mechanistically, MSG-induced oxidative stress with endoplasmic reticulum stress pathways involving Xbp1s and IRE1α was observed. The effect of MSG through an increased ROS production indicates that its long-term exposure might have adverse health effect by compromising key trophoblast functions. Full article
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19 pages, 1564 KiB  
Article
Characterization of Maternal Circulating MicroRNAs in Obese Pregnancies and Gestational Diabetes Mellitus
by Anaïs Serati, Chiara Novielli, Gaia Maria Anelli, Maria Mandalari, Francesca Parisi, Irene Cetin, Renata Paleari and Chiara Mandò
Antioxidants 2023, 12(2), 515; https://doi.org/10.3390/antiox12020515 - 17 Feb 2023
Cited by 4 | Viewed by 3008
Abstract
Maternal obesity (MO) is expanding worldwide, contributing to the onset of Gestational Diabetes Mellitus (GDM). MO and GDM are associated with adverse maternal and foetal outcomes, with short- and long-term complications. Growing evidence suggests that MO and GDM are characterized by epigenetic alterations [...] Read more.
Maternal obesity (MO) is expanding worldwide, contributing to the onset of Gestational Diabetes Mellitus (GDM). MO and GDM are associated with adverse maternal and foetal outcomes, with short- and long-term complications. Growing evidence suggests that MO and GDM are characterized by epigenetic alterations contributing to the pathogenesis of metabolic diseases. In this pilot study, plasma microRNAs (miRNAs) of obese pregnant women with/without GDM were profiled at delivery. Nineteen women with spontaneous singleton pregnancies delivering by elective Caesarean section were enrolled: seven normal-weight (NW), six obese without comorbidities (OB/GDM(−)), and six obese with GDM (OB/GDM(+)). miRNA profiling with miRCURY LNA PCR Panel allowed the analysis of the 179 most expressed circulating miRNAs in humans. Data acquisition and statistics (GeneGlobe and SPSS software) and Pathway Enrichment Analysis (PEA) were performed. Data analysis highlighted patterns of significantly differentially expressed miRNAs between groups: OB/GDM(−) vs. NW: n = 4 miRNAs, OB/GDM(+) vs. NW: n = 1, and OB/GDM(+) vs. OB/GDM(−): n = 14. For each comparison, PEA revealed pathways associated with oxidative stress and inflammation, as well as with nutrients and hormones metabolism. Indeed, miRNAs analysis may help to shed light on the complex epigenetic network regulating metabolic pathways in both the mother and the foeto-placental unit. Future investigations are needed to deepen the pregnancy epigenetic landscape in MO and GDM. Full article
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13 pages, 2502 KiB  
Article
Evidence of Increased Oxidative Stress in the Placental Tissue of Women Who Suffered an Episode of Psychosis during Pregnancy
by Miguel A. Ortega, Oscar Fraile-Martinez, Cielo García-Montero, Sonia Rodriguez-Martín, Rosa M. Funes Moñux, Coral Bravo, Juan A. De Leon-Luis, Jose V. Saz, Miguel A. Saez, Luis G. Guijarro, Guillermo Lahera, Jorge Monserrat, Fernando Mora, Javier Quintero, Julia Bujan, Natalio García-Honduvilla, Melchor Alvarez-Mon and Miguel Angel Alvarez-Mon
Antioxidants 2023, 12(1), 179; https://doi.org/10.3390/antiox12010179 - 12 Jan 2023
Cited by 4 | Viewed by 2102
Abstract
Psychosis is a complex clinical syndrome resulting in a loss of contact with reality and alterations in behavior and sensorial and motor functions. Although the onset of psychosis can be related to any medical condition, most cases of psychosis are not fully understood. [...] Read more.
Psychosis is a complex clinical syndrome resulting in a loss of contact with reality and alterations in behavior and sensorial and motor functions. Although the onset of psychosis can be related to any medical condition, most cases of psychosis are not fully understood. Psychosis may manifest for the first time during pregnancy, which is detrimental to maternofetal well-being. The impact of having a first episode of psychosis during pregnancy on the placenta has not yet been explored. Oxidative stress is thought to take part in the etiopathogenesis of this complex disorder, and this condition can also affect the placenta as it is highly sensitive to changes in the maternal environment. In this sense, the aim of the present work was to study the gene and protein expression through RT–qPCR and immunohistochemistry, respectively, of oxidative stress markers (NOX-1, NOX-2, iNOS, eNOS and PARP) in the placental tissue of women who underwent a first episode of psychosis during pregnancy (FE-PW) in comparison to healthy pregnant women. Our results showed augmented gene and protein expression of NOX-1, NOX-2, iNOS and PARP in the placental tissue of FE-PW. For the first time, we demonstrated that oxidative stress may have an important pathophysiological role in this tissue, aiding in explaining the impact of psychosis on pregnancy and the need for future studies in this field to guide better clinical management of these patients. Full article
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13 pages, 4003 KiB  
Article
Irregular Expression of Cellular Stress Response Markers in the Placenta of Women with Chronic Venous Disease
by Cielo García-Montero, Oscar Fraile-Martinez, Sonia Rodriguez-Martín, Rosa M. Funes Moñux, Jose V. Saz, Coral Bravo, Juan A. De Leon-Luis, María Ruiz-Minaya, Leonel Pekarek, Miguel A. Saez, Alberto García-Lledo, Melchor Alvarez-Mon, Julia Bujan, Natalio García-Honduvilla and Miguel A. Ortega
Antioxidants 2022, 11(11), 2277; https://doi.org/10.3390/antiox11112277 - 17 Nov 2022
Cited by 10 | Viewed by 1925
Abstract
Pregnancy comprises a period in a woman’s life in which the circulatory system is subjected to hemodynamical and biochemical changes. During this period, while restructuring blood vessels and exchanging maternal-fetal products there is an increased risk of developing chronic venous disease (CVD), which [...] Read more.
Pregnancy comprises a period in a woman’s life in which the circulatory system is subjected to hemodynamical and biochemical changes. During this period, while restructuring blood vessels and exchanging maternal-fetal products there is an increased risk of developing chronic venous disease (CVD), which may have an echo in life after childbirth for both mother and child. Previously, we investigated that pregnancy-associated CVD involves changes in placental architecture at angiogenesis, lymphangiogenesis and villi morphology compared with healthy controls (HC) with no history of CVD. We aimed to more deeply investigate the oxidative stress response in placenta from women with CVD versus HC through several markers (NRF2, KEAP1, CUL3, GSK-3β). An observational, analytical, and prospective cohort study was conducted on 114 women in their third trimester of pregnancy (32 weeks). A total of 62 participants were clinically diagnosed with CVD. In parallel, 52 controls with no history of CVD (HC) were studied. Gene and protein expressions of NRF2, KEAP1, CUL3, GSK-3β were analyzed by real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry. Nrf2 gene and protein expression was significantly greater in placental villi of women with CVD, while Keap1, CUL-3 and GSK-3β gene and protein expressions were significantly lower. Our results defined an aberrant gene and protein expression of Nrf2 and some of their main regulators Keap1, CUL-3 and GSK-3 β in the placenta of women with CVD, which could be an indicator of an oxidative environment observed in this tissue. Full article
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19 pages, 2897 KiB  
Article
Sex-Dependent Responses to Maternal Exposure to PM2.5 in the Offspring
by Hui Chen, David Van Reyk, Annabel Oliveira, Yik Lung Chan, Stephanie EL Town, Benjamin Rayner, Carol A Pollock, Sonia Saad, Jacob George, Matthew P Padula and Brian G Oliver
Antioxidants 2022, 11(11), 2255; https://doi.org/10.3390/antiox11112255 - 15 Nov 2022
Cited by 4 | Viewed by 2410
Abstract
Objective: Particulate matter (PM) with a diameter of 2.5 μm or less (PM2.5) can cross the blood-placental barrier causing adverse foetal outcomes. However, the impact of maternal exposure to low-levels of PM2.5 on liver health and the metabolic profile [...] Read more.
Objective: Particulate matter (PM) with a diameter of 2.5 μm or less (PM2.5) can cross the blood-placental barrier causing adverse foetal outcomes. However, the impact of maternal exposure to low-levels of PM2.5 on liver health and the metabolic profile is unclear. This study aimed to investigate hepatic responses to long-term gestational low-dose PM2.5 exposure, and whether the removal of PM after conception can prevent such effects. Method: Female Balb/c mice (8 weeks) were exposed to PM2.5 (5 μg/day) for 6 weeks prior to mating, during gestation and lactation to model living in a polluted environment (PM group). In a sub-group, PM2.5 exposure was stopped post-conception to model mothers moving to areas with clean air (pre-gestation, Pre) group. Livers were studied in 13-week old offspring. Results: Female offspring in both PM and Pre groups had increased liver triglyceride and glycogen levels, glucose intolerance, but reduced serum insulin and insulin resistance. Male offspring from only the Pre group had increased liver and serum triglycerides, increased liver glycogen, glucose intolerance and higher fasting glucose level. Markers of oxidative stress and inflammation were increased in females from PM and Pre groups. There was also a significant sex difference in the hepatic response to PM2.5 with differential changes in several metabolic markers identified by proteomic analysis. Conclusions: Maternal PM exposure exerted sex-dependent effects on liver health with more severe impacts on females. The removal of PM2.5 during gestation provided limited protection in the offspring’s metabolism regardless of sex. Full article
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Review

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14 pages, 1568 KiB  
Review
Role of Oxidative Stress and Inflammation in Gestational Diabetes Mellitus
by Renata Saucedo, Clara Ortega-Camarillo, Aldo Ferreira-Hermosillo, Mary Flor Díaz-Velázquez, Claudia Meixueiro-Calderón and Jorge Valencia-Ortega
Antioxidants 2023, 12(10), 1812; https://doi.org/10.3390/antiox12101812 - 29 Sep 2023
Cited by 14 | Viewed by 2982
Abstract
Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. It is related to several gestational and fetal adverse outcomes. Moreover, women with GDM and their infants have a high risk of developing type 2 diabetes in the future. The pathogenesis [...] Read more.
Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. It is related to several gestational and fetal adverse outcomes. Moreover, women with GDM and their infants have a high risk of developing type 2 diabetes in the future. The pathogenesis of GDM is not completely understood; nevertheless, two factors that contribute to its development are oxidative stress and inflammation. Oxidative stress and inflammation are related; reactive oxygen species (ROS) production can activate inflammatory cells and enhance the production of inflammatory mediators. Inflammation, in turn, leads to an increased ROS release, causing a vicious circle to ensue. Inflammatory responses can be achieved via the activation of the NF-κB signaling pathway. Herein, we review the English literature regarding oxidative stress and inflammation evaluated simultaneously in the same population, attempting to identify mechanisms through which these factors contribute to the development of GDM. Furthermore, the modulation of oxidative stress and inflammation by different therapies used in women with GDM and in cell models of GDM is included in the review. Probiotics and nutrient supplementations have been shown to reduce biomarkers of inflammation and oxidative stress in vitro and in women with GDM. Full article
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23 pages, 2727 KiB  
Review
Microbiome Changes in Pregnancy Disorders
by Luca Giannella, Camilla Grelloni, Dayana Quintili, Alessia Fiorelli, Ramona Montironi, Sonila Alia, Giovanni Delli Carpini, Jacopo Di Giuseppe, Arianna Vignini and Andrea Ciavattini
Antioxidants 2023, 12(2), 463; https://doi.org/10.3390/antiox12020463 - 12 Feb 2023
Cited by 14 | Viewed by 6620
Abstract
The human microbiota comprises all microorganisms, such as bacteria, fungi, and viruses, found within a specific environment that live on our bodies and inside us. The last few years have witnessed an explosion of information related to the role of microbiota changes in [...] Read more.
The human microbiota comprises all microorganisms, such as bacteria, fungi, and viruses, found within a specific environment that live on our bodies and inside us. The last few years have witnessed an explosion of information related to the role of microbiota changes in health and disease. Even though the gut microbiota is considered the most important in maintaining our health, other regions of the human body, such as the oral cavity, lungs, vagina, and skin, possess their own microbiota. Recent work suggests a correlation between the microbiota present during pregnancy and pregnancy complications. The aim of our literature review was to provide a broad overview of this growing and important topic. We focused on the most significant changes in the microbiota in the four more common obstetric diseases affecting women’s health. Thus, our attention will be focused on hypertensive disorders, gestational diabetes mellitus, preterm birth, and recurrent miscarriage. Pregnancy is a unique period in a woman’s life since the body undergoes different adaptations to provide an optimal environment for fetal growth. Such changes also involve all the microorganisms, which vary in composition and quantity during the three trimesters of gestation. In addition, special attention will be devoted to the potential and fundamental advances in developing clinical applications to prevent and treat those disorders by modulating the microbiota to develop personalized therapies for disease prevention and tailored treatments. Full article
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28 pages, 1381 KiB  
Review
Effect of Resveratrol on Pregnancy, Prenatal Complications and Pregnancy-Associated Structure Alterations
by Iman Ramli, Anna Maria Posadino, Roberta Giordo, Grazia Fenu, Manal Fardoun, Rabah Iratni, Ali H. Eid, Hatem Zayed and Gianfranco Pintus
Antioxidants 2023, 12(2), 341; https://doi.org/10.3390/antiox12020341 - 31 Jan 2023
Cited by 11 | Viewed by 6621
Abstract
Adverse pregnancy outcomes are considered significant health risks for pregnant women and their offspring during pregnancy and throughout their lifespan. These outcomes lead to a perturbated in-utero environment that impacts critical phases of the fetus’s life and correlates to an increased risk of [...] Read more.
Adverse pregnancy outcomes are considered significant health risks for pregnant women and their offspring during pregnancy and throughout their lifespan. These outcomes lead to a perturbated in-utero environment that impacts critical phases of the fetus’s life and correlates to an increased risk of chronic pathological conditions, such as diabetes, obesity, and cardiovascular diseases, in both the mother’s and adult offspring’s life. The dietary intake of naturally occurring antioxidants promotes health benefits and disease prevention. In this regard, maternal dietary intake of polyphenolic antioxidants is linked to a reduced risk of maternal obesity and cardio-metabolic disorders, positively affecting both the fetus and offspring. In this work, we will gather and critically appraise the current literature highlighting the effect/s of the naturally occurring polyphenol antioxidant resveratrol on oxidative stress, inflammation, and other molecular and physiological phenomena associated with pregnancy and pregnancy conditions, such as gestational diabetes, preeclampsia, and preterm labor. The resveratrol impact on prenatal complications and pregnancy-associated structures, such as the fetus and placenta, will also be discussed. Finally, we will draw conclusions from the current knowledge and provide future perspectives on potentially exploiting resveratrol as a therapeutic tool in pregnancy-associated conditions. Full article
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Jump to: Research, Review

16 pages, 2728 KiB  
Systematic Review
The Impact of a Very Short Abstinence Period on Assisted Reproductive Technique Outcomes: A Systematic Review and Meta-Analysis
by Federica Barbagallo, Rossella Cannarella, Andrea Crafa, Sandro La Vignera, Rosita A. Condorelli, Claudio Manna and Aldo E. Calogero
Antioxidants 2023, 12(3), 752; https://doi.org/10.3390/antiox12030752 - 20 Mar 2023
Cited by 5 | Viewed by 3524
Abstract
Background: Previous studies supported the beneficial effects of a very short abstinence period on sperm quality. This systematic review and meta-analysis aimed to evaluate the effects of a very short abstinence period (within 4 h) on assisted reproductive technique (ART) outcomes. Methods: A [...] Read more.
Background: Previous studies supported the beneficial effects of a very short abstinence period on sperm quality. This systematic review and meta-analysis aimed to evaluate the effects of a very short abstinence period (within 4 h) on assisted reproductive technique (ART) outcomes. Methods: A literature search was performed using the Pubmed, Scopus, Web of Science, and Cochrane databases. A meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) for randomized controlled trials (RCTs). All eligible studies were selected following the PICOS (Population, Intervention, Comparison/Comparator, Outcomes, Study type) model. The following pregnancy outcomes after ART were considered: fertilization rate (FR), implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR). This study was registered on PROSPERO (CRD42023396429). Results: We evaluated 414 records for eligibility, and 7 studies were ultimately included. Our analysis showed that a very short abstinence period significantly increased the IR, CPR, and LBR after ART. No significant differences were found for the FR and MR. Conclusions: A second ejaculation collected very shortly after the first one could represent a simple strategy to improve the results of ART, especially in couples including patients with abnormal sperm parameters. Full article
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