核因子红细胞系2相关因子2 (Nrf2)在病理性妊娠中的作用
The Role of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in Pathological Pregnancy
DOI: 10.12677/hjbm.2024.142022, PDF,   
作者: 焦芙蓉, 陈雪梅*:重庆医科大学,公共卫生学院,生殖与发育教育部国际合作联合实验室,重庆;徐翰婷:重庆医科大学,基础医学院,生殖与发育教育部国际合作联合实验室,重庆
关键词: Nrf2氧化应激不良妊娠结局生殖毒性Nrf2 Oxidative Stress Adverse Pregnancy Outcome Genotoxicity
摘要: 活性氧的产生和抗氧化还原系统之间的稳态平衡在维持正常妊娠中发挥重要作用,氧化还原系统的失衡会导致各种不良妊娠结局。核因子红细胞系2相关因子2 (nuclear factor erythroid 2-related factor 2, Nrf2)是一种抗氧化关键转录因子,活化的Nrf2可与抗氧化反应元件ARE结合激活各种抗氧化基因,增强细胞的先天抗氧化状态,维持机体氧化还原动态平衡,从而减少怀孕期间各种不利因素对母体及胎儿细胞的氧化应激和炎症损伤。本研究对Nrf2在先兆子痫、IUGR、流产、早产、妊娠期GDM和代谢综合征以及预防孕期环境毒素诱导的不良妊娠结局中的作用进行综述,并分析Nrf2在各种不良妊娠结局(APOs)中可能的作用机制。
Abstract: The homeostatic balance between the production of reactive oxygen species and the antiredox system plays an important role in maintaining a normal pregnancy, and the imbalance of the redox system leads to a variety of adverse pregnancy outcomes. Nuclear factor erythrocyte 2 related factor 2 (Nrf2) is a key antioxidant transcription factor, activated Nrf2 can combine with antioxidant response element ARE activate various antioxidant genes, enhance the innate antioxidant status of cells, maintain the body redox dynamic balance, during pregnancy to reduce various adverse factors on the maternal and fetal cell oxidative stress and inflammation damage. In this study, the role of Nrf2 in pre-eclampsia, IUGR, abortion, preterm birth, GDM and metabolic syndrome during pregnancy, and prevention of environmental toxin-induced adverse pregnancy outcomes during pregnancy were reviewed, and analyzed the possible mechanisms of Nrf2 in various adverse pregnancy outcomes (APOs).
文章引用:焦芙蓉, 徐翰婷, 陈雪梅. 核因子红细胞系2相关因子2 (Nrf2)在病理性妊娠中的作用[J]. 生物医学, 2024, 14(2): 201-211. https://doi.org/10.12677/hjbm.2024.142022

参考文献

[1] Marshall, N.E., Abrams, B., Barbour, L.A., et al. (2022) The Importance of Nutrition in Pregnancy and Lactation: Lifelong Consequences. American Journal of Obstetrics & Gynecology, 226, 607-632. [Google Scholar] [CrossRef] [PubMed]
[2] Papageorghiou, A.T., Kennedy, S.H., Salomon, L.J., et al. (2018) The INTERGROWTH-21 Fetal Growth Standards: Toward the Global Integration of Pregnancy and Pediatric Care. American Journal of Obstetrics & Gynecology, 218, S630-S640. [Google Scholar] [CrossRef] [PubMed]
[3] Nabhan, A.F. and Abdelmoula, Y.A. (2008) Amniotic Fluid Index versus Single Deepest Vertical Pocket as a Screening Test for Preventing Adverse Pregnancy Outcome. Cochrane Database Syst Rev, No. 3, CD006593. [Google Scholar] [CrossRef
[4] Shi, M., Chen, Z., Chen, M., et al. (2021) Continuous Activation of Polymorphonuclear Myeloid-Derived Suppressor Cells during Pregnancy Is Critical for Fetal Development. Cellular & Molecular Immunology, 18, 1692-1707. [Google Scholar] [CrossRef] [PubMed]
[5] Joo, E.H., Kim, Y.R., Kim, N., Jung, J.E., Han, S.H. and Cho, H.Y. (2021) Effect of Endogenic and Exogenic Oxidative Stress Triggers on Adverse Pregnancy Outcomes: Preeclampsia, Fetal Growth Restriction, Gestational Diabetes Mellitus and Preterm Birth. International Journal of Molecular Sciences, 22, Article 10122. [Google Scholar] [CrossRef] [PubMed]
[6] Quan, J.H., Gao, F.F., Ma, T.Z., et al. (2023) Toxoplasma gondii Induces Pyroptosis in Human Placental Trophoblast and Amniotic Cells by Inducing ROS Production and Activation of Cathepsin B and NLRP1/NLRP3/NLRC4/AIM2 Inflammasome. The American Journal of Pathology, 193, 2047-2065. [Google Scholar] [CrossRef] [PubMed]
[7] Menon, R., Boldogh, I., Urrabaz-Garza, R., et al. (2013) Senescence of Primary Amniotic Cells via Oxidative DNA Damage. PLOS ONE, 8, e83416. [Google Scholar] [CrossRef] [PubMed]
[8] Duhig, K., Chappell, L.C. and Shennan, A.H. (2016) Oxidative Stress in Pregnancy and Reproduction. Obstetric Medicine, 9, 113-116. [Google Scholar] [CrossRef
[9] Al-Gubory, K.H., Fowler, P.A. and Garrel, C. (2010) The Roles of Cellular Reactive Oxygen Species, Oxidative Stress and Antioxidants in Pregnancy Outcomes. The International Journal of Biochemistry & Cell Biology, 42, 1634-1650. [Google Scholar] [CrossRef] [PubMed]
[10] Sağol, S., Özkinay, E. and Özşener, S. (1999) Impaired Antioxidant Activity in Women with Pre-Eclampsia. International Journal of Gynecology & Obstetrics, 64, 121-127. [Google Scholar] [CrossRef
[11] De Oliveira, L.G., Karumanchi, A. and Sass, N. (2010) Preeclampsia: Oxidative Stress, Inflammation and Endothelial Dysfunction. Revista Brasileira de Ginecologia e Obstetrícia, 32, 609-616. [Google Scholar] [CrossRef
[12] Menon, R. and Richardson, L.S. (2017) Preterm Prelabor Rupture of the Membranes: A Disease of the Fetal Membranes. Seminars in Perinatology, 41, 409-419. [Google Scholar] [CrossRef] [PubMed]
[13] Moore, T.A., Ahmad, I.M. and Zimmerman, M.C. (2018) Oxidative Stress and Preterm Birth: An Integrative Review. Biological Research for Nursing, 20, 497-512. [Google Scholar] [CrossRef] [PubMed]
[14] Ma, Q. (2013) Role of Nrf2 in Oxidative Stress and Toxicity. Annual Review of Pharmacology and Toxicology, 53, 401-426. [Google Scholar] [CrossRef] [PubMed]
[15] Bellezza, I., Giambanco, I., Minelli, A. and Donato, R. (2018) Nrf2-Keap1 Signaling in Oxidative and Reductive Stress. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research, 1865, 721-733. [Google Scholar] [CrossRef] [PubMed]
[16] Kweider, N., Wruck, C.J. and Rath, W. (2013) New Insights into the Pathogenesis of Preeclampsia—The Role of Nrf2 Activators and Their Potential Therapeutic Impact. Geburtshilfe und Frauenheilkunde, 73, 1236-1240. [Google Scholar] [CrossRef] [PubMed]
[17] Kweider, N., Huppertz, B., Kadyrov, M., Rath, W., Pufe, T. and Wruck, C.J. (2014) A Possible Protective Role of Nrf2 in Preeclampsia. Annals of Anatomy, 196, 268-277. [Google Scholar] [CrossRef] [PubMed]
[18] Lu, J., Wang, Z., Cao, J., Chen, Y. and Dong, Y. (2018) A Novel and Compact Review on the Role of Oxidative Stress in Female Reproduction. Reproductive Biology and Endocrinology, 16, Article No. 80. [Google Scholar] [CrossRef] [PubMed]
[19] Hussain, T., Tan, B., Liu, G., et al. (2017) Modulatory Mechanism of Polyphenols and Nrf2 Signaling Pathway in LPS Challenged Pregnancy Disorders. Oxidative Medicine and Cellular Longevity, 2017, Article ID: 8254289. [Google Scholar] [CrossRef] [PubMed]
[20] Hadley, E.E., Richardson, L.S., Torloni, M.R. and Menon, R. (2018) Gestational Tissue Inflammatory Biomarkers at Term Labor: A Systematic Review of Literature. American Journal of Reproductive Immunology, 79, e12776. [Google Scholar] [CrossRef] [PubMed]
[21] Kweider, N., Fragoulis, A., Rosen, C., et al. (2011) Interplay between Vascular Endothelial Growth Factor (VEGF) and Nuclear Factor Erythroid 2-Related Factor-2 (Nrf2): Implications for Preeclampsia. Journal of Biological Chemistry, 286, 42863-42872. [Google Scholar] [CrossRef
[22] Pang, H., Huang, Y., Liu, Z., et al. (2011) Effect of Lipoxin A4 on Lipopolysaccharide-Induced Endothelial Hyperpermeability in Human Umbilical Vein Endothelial Cell. Chinese Journal of Obstetrics and Gynecology, 46, 199-204. [Google Scholar] [CrossRef] [PubMed]
[23] Onda, K., Tong, S., Nakahara, A., et al. (2015) Sofalcone Upregulates the Nuclear Factor (Erythroid-Derived 2)-Like 2/Heme Oxygenase-1 Pathway, Reduces Soluble fms-Like Tyrosine Kinase-1, and Quenches Endothelialdys Function: Potential Therapeutic for Preeclampsia. Hypertension, 65, 855-862. [Google Scholar] [CrossRef
[24] Chigusa, Y., Kondoh, E., Mogami, H., et al. (2016) Nrf2 Activation Inhibits Thrombin-Induced COX2 and PGE2 in Human Amnion Mesenchymal Cells. Placenta, 46, 112. [Google Scholar] [CrossRef
[25] Li, J., Zhou, J., Ye, Y., et al. (2016) Increased Heme Oxygenase-1 and Nuclear Factor Erythroid 2-Related Factor-2 in the Placenta Have a Cooperative Action on Preeclampsia. Gynecologic and Obstetric Investigation, 81, 543-551. [Google Scholar] [CrossRef] [PubMed]
[26] Gurusinghe, S., Cox, A.G., Rahman, R., et al. (2017) Resveratrol Mitigates Tro-Phoblast and Endothelial Dysfunction Partly via Activation of Nuclear Factor Erythroid 2-Related Factor-2. Placenta, 60, 74-85. [Google Scholar] [CrossRef] [PubMed]
[27] Onda, K., Tong, S., Beard, S., et al. (2017) Proton Pump Inhibitors Decrease Soluble fms-Like Tyrosine Kinase-1 and Soluble Endoglin Secretion, Decrease Hypertension, and Rescue Endothelial Dysfunction. Hypertension, 69, 457-468. [Google Scholar] [CrossRef
[28] Hobson, S.R., Gurusinghe, S., Lim, R., et al. (2018) Melatonin Improves Endothelial Function in Vitro and Prolongs Pregnancy in Women with Early-Onset Preeclampsia. Journal of Pineal Research, 65, e12508. [Google Scholar] [CrossRef] [PubMed]
[29] Caldeira-Dias, M., Montenegro, M.F., Bettiol, H., et al. (2019) Resveratrol Improves Endothelial Cell Markers Impaired by Plasma Incubation from Women Who Subsequently Develop Preeclampsia. Hypertension Research, 42, 1166-1174. [Google Scholar] [CrossRef] [PubMed]
[30] Cox, A.G., Gurusinghe, S., Abd Rahman, R., et al. (2019) Sulforaphane Improves Endothelial Function and Reduces Placental Oxidative Stress in Vitro. Pregnancy Hypertension, 16, 1-10. [Google Scholar] [CrossRef] [PubMed]
[31] Knyazev, E.N., Zakharova, G.S., Astakhova, L.A., Tsypina, I.M., Tonevitsky, A.G. and Sukhikh, G.T. (2019) Metabolic Reprogramming of Trophoblast Cells in Response to Hypoxia. Bulletin of Experimental Biology and Medicine, 166, 321-325. [Google Scholar] [CrossRef] [PubMed]
[32] Feng, H., Wang, L., Zhang, G., Zhang, Z. and Guo, W. (2020) Oxidative Stress Activated by Keap-1/Nrf2 Signaling Pathway in Pathogenesis of Preeclampsia. International Journal of Clinical and Experimental Pathology, 13, 382-392.
[33] Guo, H., Wang, Y. and Liu, D. (2020) Silibinin Ameliorats H2O2-Induced Cell Apoptosis and Oxidative Stress Response by Activating Nrf2 Signaling in Trophoblast Cells. Acta Histochemica, 122, Article 151620. [Google Scholar] [CrossRef] [PubMed]
[34] Langston-Cox, A., Muccini, A.M., Marshall, S.A., et al. (2020) Sulforaphane Improves Syncytiotrophoblast Mitochondrial Function after in Vitro Hypoxic and Superoxide Injury. Placenta, 96, 44-54. [Google Scholar] [CrossRef] [PubMed]
[35] Li, L., Li, H., Xue, J., Chen, P., Zhou, Q. and Zhang, C. (2020) Nanoparticle-Mediated Simultaneous Downregulation of Placental Nrf2 and SFlt1 Improves Maternal and Fetal Outcomes in a Preeclampsia Mouse Model. ACS Biomaterials Science & Engineering, 6, 5866-5873. [Google Scholar] [CrossRef] [PubMed]
[36] Yang, S., Zhang, R., Xing, B., Zhou, L., Zhang, P. and Song, L. (2020) Astragaloside IV Ameliorates Preeclampsia-Induced Oxidative Stress through the Nrf2/HO-1 Pathway in a Rat Model. American Journal of Physiology-Endo-crinology and Metabolism, 319, e904-e911. [Google Scholar] [CrossRef] [PubMed]
[37] Zuo, J. and Jiang, Z. (2020) Melatonin Attenuates Hypertension and Oxidative Stress in a Rat Model of L-NAME-Induced Gestational Hypertension. Vascular Medicine, 25, 295-301. [Google Scholar] [CrossRef
[38] Chigusa, Y., Tatsumi, K., Kondoh, E., et al. (2012) Decreased Lectin-Like Oxidized LDL Receptor 1 (LOX-1) and Low Nrf2 Activation in Placenta Are Involved in Preeclampsia. The Journal of Clinical Endocrinology & Metabolism, 97, e1862-e1870. [Google Scholar] [CrossRef] [PubMed]
[39] Tong, S., Kaitu’u-Lino, T.J., Onda, K., et al. (2015) Heme Oxygenase-1 Is Not Decreased in Preeclamptic Placenta and Does Not Negatively Regulate Placental Soluble fms-Like Tyrosine Kinase-1 or Soluble Endoglin Secretion. Hypertension, 66, 1073-1081. [Google Scholar] [CrossRef
[40] Nezu, M., Souma, T., Yu, L., et al. (2017) Nrf2 Inactivation Enhances Placental Angiogenesis in a Preeclampsia Mouse Model and Improves Maternal and Fetal Outcomes. Science Signaling, 10, eaam5711. [Google Scholar] [CrossRef] [PubMed]
[41] Acar, N., Soylu, H., Edizer, I., et al. (2014) Expression of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and Peroxiredoxin 6 (Prdx6) Proteins in Healthy and Pathologic Placentas of Human and Rat. Acta Histochemica, 116, 1289-1300. [Google Scholar] [CrossRef] [PubMed]
[42] Kweider, N., Huppertz, B., Wruck, C.J., et al. (2012) A Role for Nrf2 in Redox Signalling of the Invasive Extravillous Trophoblast in Severe Early Onset IUGR Associated with Preeclampsia. PLOS ONE, 7, e47055. [Google Scholar] [CrossRef] [PubMed]
[43] Wu, J., He, Z., Gao, Y., Zhang, G., Huang, X. and Fang, Q. (2017) Placental NFE2L2 Is Discordantly Activated in Monochorionic Twins with Selective Intrauterine Growth Restriction and Possibly Regulated by Hypoxia. Free Radical Research, 51, 351-359. [Google Scholar] [CrossRef] [PubMed]
[44] Yan, E., Zhang, J., Han, H., et al. (2019) Curcumin Alleviates IUGR Jejunum Damage by Increasing Antioxidant Capacity through Nrf2/Keap1 Pathway in Growing Pigs. Animals (Basel), 10, Article 41. [Google Scholar] [CrossRef] [PubMed]
[45] Niu, Y., He, J., Ahmad, H., et al. (2019) Dietary Curcumin Supplementation Increases Antioxidant Capacity, Upregulates Nrf2 and Hmox1 Levels in the Liver of Piglet Model with Intrauterine Growth Retardation. Nutrients, 11, Article 2978. [Google Scholar] [CrossRef] [PubMed]
[46] Kweider, N., Huppertz, B., Rath, W., et al. (2017) The Effects of Nrf2 Deletion on Placental Morphology and Exchange Capacity in the Mouse. The Journal of Maternal-Fetal & Neonatal Medicine, 30, 2068-2073. [Google Scholar] [CrossRef] [PubMed]
[47] Jiang, W., Wan, L., Chen, P. and Lu, W. (2021) Docosahexaenoic Acid Activates the Nrf2 Signaling Pathway to Alleviate Impairment of Szui(2020) Excessive Reactive Oxygen Species Induce Apoptosis via the APPL1-Nrf2/HO-1 Antioxidant Signalling Pathway in Trophoblasts with Missed Abortion. Life Sciences, 254, Article 117781. [Google Scholar] [CrossRef] [PubMed]
[48] Khadzhieva, M.B., Lutcenko, N.N., Volodin, I.V., Morozova, K.V. and Salnikova, L.E. (2014) Association of Oxida-tive Stress-Related Genes with Idiopathic Recurrent Miscarriage. Free Radical Research, 48, 534-541. [Google Scholar] [CrossRef] [PubMed]
[49] Luan, X., Yan, Y., Zheng, Q., et al. (2020) Excessive Reactive Oxygen Species Induce Apoptosis via the APPL1-Nrf2/HO-1 Antioxidant Signalling Pathway in Trophoblasts with Missed Abortion. Life Sciences, 254, Article 117781. [Google Scholar] [CrossRef] [PubMed]
[50] Zhang, Y., Zhao, W., Xu, H., et al. (2019) Hyperandrogenism and Insulin Resistance-Induced Fetal Loss: Evidence for Placental Mitochondrial Abnormalities and Elevated Reactive Oxygen Species Production in Pregnant Rats That Mimic the Clinical Features of Polycystic Ovary Syndrome. The Journal of Physiology, 597, 3927-3950. [Google Scholar] [CrossRef
[51] Hu, M., Zhang, Y., Guo, X., et al. (2019) Hyperandrogenism and Insulin Resistance Induce Gravid Uterine Defects in Association with Mitochondrial Dysfunction and Aberrant Reactive Oxygen Species Production. American Journal of Physiology-Endocrinology and Metabolism, 316, e794-e809. [Google Scholar] [CrossRef] [PubMed]
[52] Sussan, T.E., Sudini, K., Talbot Jr., C.C., et al. (2017) Nrf2 Regulates Gene-Environment Interactions in an Animal Model of Intrauterine Inflammation: Implications for Preterm Birth and Prematurity. Scientific Reports, 7, Article No. 40194. [Google Scholar] [CrossRef] [PubMed]
[53] Kadam, L., Gomez-Lopez, N., Mial, TN., et al. (2017) Rosiglitazone Regulates TLR4 and Rescues HO-1 and NRF2 Expression in Myometrial and Decidual Macrophages in Inflammation-Induced Preterm Birth. Reproductive Sciences, 24, 1590-1599. [Google Scholar] [CrossRef] [PubMed]
[54] Zhang, W., Li, M., Li, N. and Liu, Z. (2020) Regulation of Keap-1/Nrf2 Signaling Pathway Is Activated by Oxidative Stress in Patients with Premature Rupture of Membranes. Medical Science Monitor, 26, e921757. [Google Scholar] [CrossRef
[55] Mogami, H., Keller, P.W., Shi, H. and Word, R.A. (2014) Effect of Thrombin on Human Amnion Mesenchymal Cells, Mouse Fetal Membranes, and Preterm Birth. Journal of Biological Chemistry, 289, 13295-13307. [Google Scholar] [CrossRef
[56] Chigusa, Y., Kishore, A.H., Mogami, H. and Word, R.A. (2016) Nrf2 Activation Inhibits Effects of Thrombin in Human Amnion Cells and Thrombin-Induced Preterm Birth in Mice. The Journal of Clinical Endocrinology & Metabolism, 101, 2612-2621. [Google Scholar] [CrossRef] [PubMed]
[57] Gusar, V.A., Timofeeva, A.V., Chagovets, V.V., et al. (2022) Interrelation between miRNAs Expression Associated with Redox State Fluctuations, Immune and Inflammatory Response Activation, and Neonatal Outcomes in Complicated Pregnancy, Accompanied by Placental Insufficiency. Antioxidants (Basel), 12, Article 6. [Google Scholar] [CrossRef] [PubMed]
[58] Duan, Y., Sun, F., Que, S., Li, Y., Yang, S. and Liu, G. (2018) Prepregnancy Maternal Diabetes Combined with Obesity Impairs Placental Mitochondrial Function Involving Nrf2/ARE Pathway and Detrimentally Alters Metabolism of Offspring. Obesity Research & Clinical Practice, 12, 90-100. [Google Scholar] [CrossRef] [PubMed]
[59] Manoharan, B., Bobby, Z., Dorairajan, G., et al. (2019) Increased Placental Expressions of Nuclear Factor Erythroid 2-Related Factor 2 and Antioxidant Enzymes in Gestational Diabetes: Protective Mechanisms against the Placental Oxidative Stress? European Journal of Obstetrics & Gynecology and Reproductive Biology, 238, 78-85. [Google Scholar] [CrossRef] [PubMed]
[60] Zhang, C., Yang, Y., Chen, R., et al. (2019) Aberrant Expression of Oxidative Stress Related Proteins Affects the Pregnancy Outcome of Gestational Diabetes Mellitus Patients. American Journal of Translational Research, 11, 269-279.
[61] He, M.-Y., Wang, G., Han, S.-S., et al. (2016) Nrf2 Signalling and Autophagy Are Involved in Diabetes Mellitus-In-duced Defects in the Development of Mouse Placenta. Open Biology, 6, Article 160064. [Google Scholar] [CrossRef] [PubMed]
[62] McAninch, D., Bianco-Miotto, T., Gatford, K.L., et al. (2020) The Metabolic Syndrome in Pregnancy and Its Association with Child Telomere Length. Diabetologia, 63, 2140-2149. [Google Scholar] [CrossRef] [PubMed]
[63] Zheng, J., Liu, X., Zheng, B., et al. (2020) Maternal 25-Hydroxyvitamin D Deficiency Promoted Metabolic Syndrome and Downregulated Nrf2/CBR1 Pathway in Offspring. Frontiers in Pharmacology, 11, Article 97. [Google Scholar] [CrossRef] [PubMed]
[64] Sun, C.C., Lai, Y.N., Wang, W.H., et al. (2020) Metformin Ameliorates Gestational Diabetes Mellitus-Induced Endothelial Dysfunction via Downregulation of P65 and Upregulation of Nrf2. Frontiers in Pharmacology, 11, Article 575390. [Google Scholar] [CrossRef] [PubMed]
[65] Song, H., Xu, Y., Yang, X., Rong, X., Wang, Y. and Wei, N. (2019) Tertiary Butylhydroquinone Alleviates Gestational Diabetes Mellitus in C57BL/KsJ-Lep db/ Mice by Suppression of Oxidative Stress. Journal of Cellular Biochemistry, 120, 15310-15319. [Google Scholar] [CrossRef] [PubMed]
[66] Srám, R.J., Binková, B., Dejmek, J. and Bobak, M. (2005) Ambient Air Pollution and Pregnancy Outcomes: A Review of the Literature. Environmental Health Perspectives, 113, 375-382. [Google Scholar] [CrossRef] [PubMed]
[67] Nagiah, S., Phulukdaree, A., Naidoo, D., et al. (2015) Oxidative Stress and Air Pollution Exposure during Pregnancy: A Molecular Assessment. Human & Experimental Toxicology, 34, 838-847. [Google Scholar] [CrossRef] [PubMed]
[68] Chiapella, G., Flores-Martín, J., Ridano, M.E., et al. (2013) The Organophosphate Chlorpyrifos Disturbs Redox Balance and Triggers Antioxidant Defense Mechanisms in JEG-3 Cells. Placenta, 34, 792-798. [Google Scholar] [CrossRef] [PubMed]
[69] Chiapella, G., Genti-Raimondi, S. and Magnarelli, G. (2014) Placental Oxidative Status in Rural Residents Environmentally Exposed to Organophosphates. Environmental Toxicology and Pharmacology, 38, 220-229. [Google Scholar] [CrossRef] [PubMed]
[70] Suter, M.A., Aagaard, K.M., Coarfa, C., et al. (2019) Association between Elevated Placental Polycyclic Aromatic Hydrocarbons (PAHs) and PAH-DNA Adducts from Superfund Sites in Harris County, and Increased Risk of Preterm Birth (PTB). Biochemical and Biophysical Research Communications, 516, 344-349. [Google Scholar] [CrossRef] [PubMed]
[71] Ponniah, M., Billett, E.E. and de Girolamo, L.A. (2015) Bisphenol A Increases BeWo Trophoblast Survival in Stress-Induced Paradigms through Regulation of Oxidative Stress and Apoptosis. Chemical Research in Toxicology, 28, 1693-1703. [Google Scholar] [CrossRef] [PubMed]
[72] Park, H.-R. and Loch-Caruso, R. (2014) Protective Effect of Nuclear Factor E2-Related Factor 2 on Inflammatory Cytokine Response to Brominated Diphenyl Ether-47 in the HTR-8/SVneo Human First Trimester Extravillous Trophoblast Cell Line. Toxicology and Applied Pharmacology, 281, 67-77. [Google Scholar] [CrossRef] [PubMed]
[73] Harris, C. and Hansen, J.M. (2012) Nrf2-Mediated Resistance to Oxidant-Induced Redox Disruption in Embryos. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 95, 213-218. [Google Scholar] [CrossRef] [PubMed]
[74] Dong, Q., Hou, H., Wu, J. and Chen, Y. (2016) The Nrf2-ARE Pathway Is Associated with Schisandrin B Attenuating Benzo(a)pyrene-Induced HTR Cells Damages in Vitro. Environmental Toxicology, 31, 1439-1449. [Google Scholar] [CrossRef] [PubMed]
[75] Zhao, F., Lei, F., Yan, X., Zhang, S., Wang, W. and Zheng, Y. (2018) Protective Effects of Hydrogen Sulfide against Cigarette Smoke Exposure-Induced Placental Oxidative Damage by Alleviating Redox Imbalance via Nrf2 Pathway in Rats. Cellular Physiology and Biochemistry, 48, 1815-1828. [Google Scholar] [CrossRef] [PubMed]
[76] Qi, L., Jiang, J., Zhang, J., Zhang, L. and Wang, T. (2020) Curcumin Protects Human Trophoblast HTR8/SVneo Cells from H2O2-Induced Oxidative Stress by Activating Nrf2 Signaling Pathway. Antioxidants (Basel), 9, Article 121. [Google Scholar] [CrossRef] [PubMed]
[77] Chigusa, Y., Kawasaki, K., Kondoh, E., et al. (2016) Simvastatin Inhibits Oxidative Stress via the Activation of Nuclear Factor Erythroid 2-Related Factor 2 Signaling in Trophoblast Cells. Journal of Obstetrics and Gynaecology Research, 42, 36-43. [Google Scholar] [CrossRef] [PubMed]
[78] Sagrillo-Fagundes, L., Bienvenue-Pariseault, J. and Vaillancourt, C. (2019) Melatonin: The Smart Molecule That Differentially Modulates Autophagy in Tumor and Normal Placental Cells. PLOS ONE, 14, e0202458. [Google Scholar] [CrossRef] [PubMed]
[79] Manuel, C.R., Charron, M.J., Ashby Jr., C.R. and Reznik, S.E. (2018) Saturated and Unsaturated Fatty Acids Differentially Regulate in Vitro and ex Vivo Placental Antioxidant Capacity. American Journal of Reproductive Immunology, 80, e12868. [Google Scholar] [CrossRef] [PubMed]
[80] Ono, K., Furugen, A., Kurosawa, Y., et al. (2019) Analysis of the Effects of Polyunsaturated Fatty Acids on Transporter Expressions Using a PCR Array: Induction of XCT/SLC7A11 in Human Placental BeWo Cells. Placenta, 75, 34-41. [Google Scholar] [CrossRef] [PubMed]
[81] Brewer, A.C., Mustafi, S.B., Murray, T.V.A., Rajasekaran, N.S. and Benjamin, I.J. (2012) Reductive Stress Linked to Small HSPs, G6PD, and Nrf2 Pathways in Heart Disease. Antioxidants & Redox Signaling, 18, 1114-1127. [Google Scholar] [CrossRef] [PubMed]
[82] Menon, R. and Peltier, M.R. (2020) Novel Insights into the Regulatory Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 in Oxidative Stress and Inflammation of Human Fetal Membranes. International Journal of Molecular Sciences, 21, Article 6139. [Google Scholar] [CrossRef] [PubMed]