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铁死亡（ferroptosis）是一种特殊的细胞死亡方式，其发生与铁的依赖性密切相关。子痫前期（preeclampsia， PE）是一种妊娠期特有的疾病，与母体和胎儿的健康风险紧密相关。PE患者的血液中存在过量的铁，这可能与妊娠期间的溶血以及胎盘和血管中释放的自由基相互作用有关。过量的铁可以参与脂质过氧化反应，产生有毒的氧化产物，从而对血管内皮细胞和胎盘组织造成损伤。最近的研究表明，PE与脂质过氧化（lipid peroxidation， LPO）和铁死亡之间存在密切的关系。LPO是指多不饱和脂肪酸与自由基反应，导致细胞膜损伤和炎症反应。综上所述，PE、LPO和铁死亡之间存在复杂的相互关系。进一步研究这些关系对于理解子痫前期的病理机制和制定新的治疗策略具有重要意义，有望为预防和治疗子痫前期提供新的靶点和策略。
","endNoteUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=EndNote&id=753","reference":"| 1 | Bangi EF， Yousuf MH， Upadhyay S， et al. Comprehensive review of hypertensive disorders related to pregnancy［J］. South Med J， 2023， 116（6）： 482. |
| 2 | Phipps EA， Thadhani R， Benzing T， et al. Author correction： pre-eclampsia： pathogenesis， novel diagnostics and therapies［J］. Nat Rev Nephrol， 2019， 15（6）： 386. |
| 3 | Michalczyk M， Celewicz A， Celewicz M， et al. The role of inflammation in the pathogenesis of preeclampsia［J］. Mediators Inflamm， 2020， 2020： 3864941. |
| 4 | Hu MY， Li J， Baker PN， et al. Revisiting preeclampsia： a metabolic disorder of the placenta［J］. FEBS J， 2022， 289（2）： 336. |
| 5 | Luo EF， Li HX， Qin YH， et al. Role of ferroptosis in the process of diabetes-induced endothelial dysfunction［J］. World J Diabetes， 2021， 12（2）： 124. |
| 6 | Toyokuni S， Ito F， Yamashita K， et al. Iron and thiol redox signaling in cancer： an exquisite balance to escape ferroptosis［J］. Free Radic Biol Med， 2017， 108： 610. |
| 7 | Gumilar KE， Priangga B， Lu CH， et al. Iron metabolism and ferroptosis： a pathway for understanding preeclampsia［J］. Biomed Pharmacother， 2023， 167： 115565. |
| 8 | Que XC， Hung MY， Yeang C， et al. Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice［J］. Nature， 2018， 558（7709）： 301. |
| 9 | Brown SHJ， Eather SR， Freeman DJ， et al. A lipidomic analysis of placenta in preeclampsia： evidence for lipid storage［J］. PLoS One， 2016， 11（9）： e0163972. |
| 10 | Ortega MA， Garcia-Puente LM， Fraile-Martinez O， et al. Oxidative stress， lipid peroxidation and ferroptosis are major pathophysiological signatures in the placental tissue of women with late-onset preeclampsia［J］. Antioxidants （Basel）， 2024， 13（5）： 591. |
| 11 | Harris LK， Benagiano M， D'Elios MM， et al. Placental bed research： II. Functional and immunological investigations of the placental bed［J］. Am J Obstet Gynecol， 2019， 221（5）： 457. |
| 12 | Almasry SM， Elmansy RA， Elfayomy AK， et al. Ultrastructure alteration of decidual natural killer cells in women with unexplained recurrent miscarriage： a possible association with impaired decidual vascular remodelling［J］. J Mol Histol， 2015， 46（1）： 67. |
| 13 | Jia YH， Li T， Huang XJ， et al. Dysregulated DNA methyltransferase 3a upregulates IGFBP5 to suppress trophoblast cell migration and invasion in preeclampsia［J］. Hypertension， 2017， 69（2）： 356. |
| 14 | Chen XH， Tong C， Li HY， et al. Dysregulated expression of RPS4Y1 （ribosomal protein S4， Y-linked 1） impairs STAT3 （signal transducer and activator of transcription 3） signaling to suppress trophoblast cell migration and invasion in preeclampsia［J］. Hypertension， 2018， 71（3）： 481. |
| 15 | de Almeida LGN， Young D， Chow L， et al. Proteomics and metabolomics profiling of platelets and plasma mediators of thrombo-inflammation in gestational hypertension and preeclampsia［J］. Cells， 2022， 11（8）： 1256. |
| 16 | Lee S， Shin J， Kim JS， et al. Targeting TBK1 attenuates LPS-Induced NLRP3 inflammasome activation by regulating of mTORC1 pathways in trophoblasts［J］. Front Immunol， 2021， 12： 743700. |
| 17 | Cheng SB， Nakashima A， Huber WJ， et al. Pyroptosis is a critical inflammatory pathway in the placenta from early onset preeclampsia and in human trophoblasts exposed to hypoxia and endoplasmic reticulum stressors［J］. Cell Death Dis， 2019， 10（12）： 927. |
| 18 | Pereira MM， Torrado J， Sosa C， et al. Shedding light on the pathophysiology of preeclampsia-syndrome in the era of cardio-obstetrics： role of inflammation and endothelial dysfunction［J］. Curr Hypertens Rev， 2022， 18（1）： 17. |
| 19 | Nieto-Orellana A， Li H， Rosiere R， et al. Targeted PEG-poly （glutamic acid） complexes for inhalation protein delivery to the lung［J］. J Control Release， 2019， 316： 250. |
| 20 | Tuli HS， Kaur J， Vashishth K， et al. Molecular mechanisms behind ROS regulation in cancer： a balancing act between augmented tumorigenesis and cell apoptosis［J］. Arch Toxicol， 2023， 97（1）： 103. |
| 21 | Zhang YJ， Lu Y， Jin LP. Iron metabolism and ferroptosis in physiological and pathological pregnancy［J］. Int J Mol Sci， 2022， 23（16）： 9395. |
| 22 | Garcia-Casal MN， Pasricha SR， Martinez RX， et al. Serum or plasma ferritin concentration as an index of iron deficiency and overload［J］. Cochrane Database Syst Rev， 2021， 5（5）： Cd011817. |
| 23 | Mégier C， Peoc'h K， Puy V， et al. Iron metabolism in normal and pathological pregnancies and fetal consequences［J］. Metabolites， 2022， 12（2）： 129. |
| 24 | Gong XL， Li JX， Jiang YH， et al. Risk of preeclampsia by gestational weight gain in women with varied prepregnancy BMI： a retrospective cohort study［J］. Front Endocrinol （Lausanne）， 2022， 13： 967102. |
| 25 | Ng SW， Norwitz SG， Norwitz ER. The impact of iron overload and ferroptosis on reproductive disorders in humans： implications for preeclampsia［J］. Int J Mol Sci， 2019， 20（13）： 3283. |
| 26 | Chen HJ， Sugiyama M， Shimokawa F， et al. Response to iron overload in cultured hepatocytes［J］. Sci Rep， 2020， 10（1）： 21184. |
| 27 | Botero JP， McIntosh JJ. Labor and delivery： DIC， HELLP， preeclampsia［J］. Hematology Am Soc Hematol Educ Program， 2023， 2023（1）： 737. |
| 28 | Liao TT， Xu X， Ye X， et al. DJ-1 upregulates the Nrf2/GPX4 signal pathway to inhibit trophoblast ferroptosis in the pathogenesis of preeclampsia［J］. Sci Rep， 2022， 12（1）： 2934. |
| 29 | Hodyl NA， Aboustate N， Bianco-Miotto T， et al. Child neurodevelopmental outcomes following preterm and term birth： what can the placenta tell us？［J］. Placenta， 2017， 57： 79. |
| 30 | Rana S， Lemoine E， Granger JP， et al. Preeclampsia： pathophysiology， challenges， and perspectives［J］. Circ Res， 2019， 124（7）： 1094. |
| 31 | Staff AC. The two-stage placental model of preeclampsia： an update［J］. J Reprod Immunol， 2019， 134/135： 1. |
| 32 | Rottenstreich A， Arad A， Terespolsky H， et al. Antiphospholipid antibody profile-based outcome of purely vascular and purely obstetric antiphospholipid syndrome［J］. J Thromb Thrombolysis， 2018， 46（2）： 166. |
| 33 | Kraft VAN， Bezjian CT， Pfeiffer S， et al. GTP cyclohydrolase 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling［J］. ACS Cent Sci， 2020， 6（1）： 41. |
| 34 | Jauniaux E， Burton GJ. The role of oxidative stress in placental-related diseases of pregnancy［J］. J Gynecol Obstet Biol Reprod （Paris）， 2016， 45（8）： 775. |
| 35 | Brown MA， Magee LA， Kenny LC， et al. Hypertensive disorders of pregnancy： ISSHP classification， diagnosis， and management recommendations for international practice［J］. Hypertension， 2018， 72（1）： 24. |
| 36 | Gaschler MM， Stockwell BR. Lipid peroxidation in cell death［J］. Biochem Biophys Res Commun， 2017， 482（3）： 419. |
| 37 | Kruk J， Aboul-Enein HY， K?adna A， et al. Oxidative stress in biological systems and its relation with pathophysiological functions： the effect of physical activity on cellular redox homeostasis［J］. Free Radic Res， 2019， 53（5）： 497. |
| 38 | El-Khalik SRA， Ibrahim RR， Ghafar MTA， et al. Novel insights into the SLC7A11-mediated ferroptosis signaling pathways in preeclampsia patients： identifying pannexin 1 and toll-like receptor 4 as innovative prospective diagnostic biomarkers［J］. J Assist Reprod Genet， 2022， 39（5）： 1115. |
| 39 | Melchiorre K， Giorgione V， Thilaganathan B. The placenta and preeclampsia： villain or victim？［J］. Am J Obstet Gynecol， 2022， 226（2S）： S954. |
| 40 | Shaji Geetha N， Bobby Z， Dorairajan G， et al. Increased hepcidin levels in preeclampsia： a protective mechanism against iron overload mediated oxidative stress？［J］. J Matern Fetal Neonatal Med， 2022， 35（4）： 636. |
| 41 | Chen ZX， Gan JF， Zhang M， et al. Ferroptosis and its emerging role in pre-eclampsia［J］. Antioxidants （Basel）， 2022， 11（7）： 1282. |
| 42 | Redman CW， Sacks GP， Sargent IL. Preeclampsia： an excessive maternal inflammatory response to pregnancy［J］. Am J Obstet Gynecol， 1999， 180（2 Pt 1）： 499. |
| 43 | Wang Y， Li BX， Zhao Y. Inflammation in preeclampsia： genetic biomarkers， mechanisms， and therapeutic strategies［J］. Front Immunol， 2022， 13： 883404. |
| 44 | Staff AC， Johnsen GM， Dechend R， et al. Preeclampsia and uteroplacental acute atherosis： immune and inflammatory factors［J］. J Reprod Immunol， 2014， 101/102： 120. |
| 45 | Cornelius DC， Wallace K. Decidual natural killer cells： a critical pregnancy mediator altered in preeclampsia［J］. EBioMedicine， 2019， 39： 31. |
| 46 | Hiby SE， Apps R， Chazara O， et al. Maternal KIR in combination with paternal HLA-C2 regulate human birth weight［J］. J Immunol， 2014， 192（11）： 5069. |
| 47 | Nakimuli A， Chazara O， Hiby SE， et al. A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia［J］. Proc Natl Acad Sci U S A， 2015， 112（3）： 845. |
| 48 | Tsuda S， Zhang XX， Hamana H， et al. Clonally expanded decidual effector regulatory T cells increase in late gestation of normal pregnancy， but not in preeclampsia， in humans［J］. Front Immunol， 2018， 9： 1934. |
| 49 | Hosseini A， Dolati S， Hashemi V， et al. Regulatory T and T helper 17 cells： their roles in preeclampsia［J］. J Cell Physiol， 2018， 233（9）： 6561. |
| 50 | Miller D， Motomura K， Galaz J， et al. Cellular immune responses in the pathophysiology of preeclampsia［J］. J Leukoc Biol， 2022， 111（1）： 237. |
| 51 | Dixon SJ， Lemberg KM， Lamprecht MR， et al. Ferroptosis： an iron-dependent form of nonapoptotic cell death［J］. Cell， 2012， 149（5）： 1060. |
| 52 | Zheng QQ， Zhao YS， Guo J， et al. Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome［J］. Leuk Res， 2017， 58： 55. |
| 53 | Sangkhae V， Fisher AL， Wong S， et al. Effects of maternal iron status on placental and fetal iron homeostasis［J］. J Clin Invest， 2020， 130（2）： 625. |
| 54 | Chiarello DI， Abad C， Rojas D， et al. Oxidative stress： normal pregnancy versus preeclampsia［J］. Biochim Biophys Acta Mol Basis Dis， 2020， 1866（2）： 165354. |
| 55 | Ursini F， Maiorino M. Lipid peroxidation and ferroptosis： the role of GSH and GPx4［J］. Free Radic Biol Med， 2020， 152： 175. |
)","risUrl_cn":"//www.pitakata.com/xuebao/CN/article/getTxtFile.do?fileType=Ris&id=753","title_cn":"子痫前期铁死亡与脂质过氧化的机制","doi":"10.3969/j.issn.2097-0005.2025.02.011","jieShuYe":"128","keywordList_en":["preeclampsia","ferroptosis","lipid peroxidation","ischemia-reperfusion","oxidative stress","inflammatory response","immune response"],"endNoteUrl_cn":"//www.pitakata.com/xuebao/CN/article/getTxtFile.do?fileType=EndNote&id=753","zhaiyao_en":"Ferroptosis is a distinct form of cell death characterized by iron dependence. Preeclampsia （PE） is a severe disorder occurring during pregnancy， posing significant risks to maternal and fetal health. Excessive iron levels have been observed in the blood of PE patients， potentially arising from hemolysis during pregnancy and interactions with free radicals released from the placenta and vasculature. Excess iron can participate in lipid peroxidation reactions， generating toxic oxidative products that contribute to endothelial cell and placental tissue damage. Recent studies have highlighted a close relationship between PE， lipid peroxidation （LPO） and ferroptosis. LPO refers to the reaction between polyunsaturated fatty acids and free radicals， resulting in cell membrane damage and inflammatory responses. Collectively， the interplay among PE， lipid peroxidation， and ferroptosis is complex. Further exploration of these relationships is crucial for understanding the pathophysiology of PE and developing novel therapeutic strategies， potentially offering new targets and approaches for the prevention and treatment of preeclampsia.
","bibtexUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=BibTeX&id=753","abstractUrl_cn":"http://xuebao.sdfmu.edu.cn/CN/10.3969/j.issn.2097-0005.2025.02.011","zuoZheCn_L":"董素淼, 于豆, 魏会珍, 刘婉儿, 张娴, 王婷","juanUrl_cn":"http://xuebao.sdfmu.edu.cn/CN/Y2025","lanMu_en":"Reviews","qiUrl_en":"//www.pitakata.com/xuebao/EN/Y2025/V46/I2","zuoZhe_EN":"Sumiao DONG1, Dou YU1,3, Huizhen WEI4, Waner LIU1, Xian ZHANG1, Ting WANG2()","risUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=Ris&id=753","title_en":"Mechanistic study on the relationship between ferroptosis and lipid peroxidation in preeclampsia","hasPdf":"true"},"authorNotes_cn":["王婷，E-mail：15969709229@163.com。
Mechanistic study on the relationship between ferroptosis and lipid peroxidation in preeclampsia
Sumiao DONG, Dou YU, Huizhen WEI, Waner LIU, Xian ZHANG, Ting WANG
Journal of ShanDong First Medical University&ShanDong Academy of Medical Sciences››2025, Vol. 46››Issue (2): 123-128.
PDF(461 KB)
PDF(461 KB)
Mechanistic study on the relationship between ferroptosis and lipid peroxidation in preeclampsia
Ferroptosis is a distinct form of cell death characterized by iron dependence. Preeclampsia （PE） is a severe disorder occurring during pregnancy， posing significant risks to maternal and fetal health. Excessive iron levels have been observed in the blood of PE patients， potentially arising from hemolysis during pregnancy and interactions with free radicals released from the placenta and vasculature. Excess iron can participate in lipid peroxidation reactions， generating toxic oxidative products that contribute to endothelial cell and placental tissue damage. Recent studies have highlighted a close relationship between PE， lipid peroxidation （LPO） and ferroptosis. LPO refers to the reaction between polyunsaturated fatty acids and free radicals， resulting in cell membrane damage and inflammatory responses. Collectively， the interplay among PE， lipid peroxidation， and ferroptosis is complex. Further exploration of these relationships is crucial for understanding the pathophysiology of PE and developing novel therapeutic strategies， potentially offering new targets and approaches for the prevention and treatment of preeclampsia.
preeclampsia/ferroptosis/lipid peroxidation/ischemia-reperfusion/oxidative stress/inflammatory response/immune response
| 1 | Bangi EF， Yousuf MH， Upadhyay S， et al. Comprehensive review of hypertensive disorders related to pregnancy［J］.South Med J，2023，116（6）： 482. |
| 2 | Phipps EA， Thadhani R， Benzing T， et al. Author correction： pre-eclampsia： pathogenesis， novel diagnostics and therapies［J］.Nat Rev Nephrol，2019，15（6）： 386. |
| 3 | Michalczyk M， Celewicz A， Celewicz M， et al. The role of inflammation in the pathogenesis of preeclampsia［J］.Mediators Inflamm，2020，2020： 3864941. |
| 4 | Hu MY， Li J， Baker PN， et al. Revisiting preeclampsia： a metabolic disorder of the placenta［J］.FEBS J，2022，289（2）： 336. |
| 5 | Luo EF， Li HX， Qin YH， et al. Role of ferroptosis in the process of diabetes-induced endothelial dysfunction［J］.World J Diabetes，2021，12（2）： 124. |
| 6 | Toyokuni S， Ito F， Yamashita K， et al. Iron and thiol redox signaling in cancer： an exquisite balance to escape ferroptosis［J］.Free Radic Biol Med，2017，108： 610. |
| 7 | Gumilar KE， Priangga B， Lu CH， et al. Iron metabolism and ferroptosis： a pathway for understanding preeclampsia［J］.Biomed Pharmacother，2023，167： 115565. |
| 8 | Que XC， Hung MY， Yeang C， et al. Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice［J］.Nature，2018，558（7709）： 301. |
| 9 | Brown SHJ， Eather SR， Freeman DJ， et al. A lipidomic analysis of placenta in preeclampsia： evidence for lipid storage［J］.PLoS One，2016，11（9）： e0163972. |
| 10 | Ortega MA， Garcia-Puente LM， Fraile-Martinez O， et al. Oxidative stress， lipid peroxidation and ferroptosis are major pathophysiological signatures in the placental tissue of women with late-onset preeclampsia［J］.Antioxidants （Basel），2024，13（5）： 591. |
| 11 | Harris LK， Benagiano M， D'Elios MM， et al. Placental bed research： II. Functional and immunological investigations of the placental bed［J］.Am J Obstet Gynecol，2019，221（5）： 457. |
| 12 | Almasry SM， Elmansy RA， Elfayomy AK， et al. Ultrastructure alteration of decidual natural killer cells in women with unexplained recurrent miscarriage： a possible association with impaired decidual vascular remodelling［J］.J Mol Histol，2015，46（1）： 67. |
| 13 | Jia YH， Li T， Huang XJ， et al. Dysregulated DNA methyltransferase 3a upregulates IGFBP5 to suppress trophoblast cell migration and invasion in preeclampsia［J］.Hypertension，2017，69（2）： 356. |
| 14 | Chen XH， Tong C， Li HY， et al. Dysregulated expression of RPS4Y1 （ribosomal protein S4， Y-linked 1） impairs STAT3 （signal transducer and activator of transcription 3） signaling to suppress trophoblast cell migration and invasion in preeclampsia［J］.Hypertension，2018，71（3）： 481. |
| 15 | de Almeida LGN， Young D， Chow L， et al. Proteomics and metabolomics profiling of platelets and plasma mediators of thrombo-inflammation in gestational hypertension and preeclampsia［J］.Cells，2022，11（8）： 1256. |
| 16 | Lee S， Shin J， Kim JS， et al. Targeting TBK1 attenuates LPS-Induced NLRP3 inflammasome activation by regulating of mTORC1 pathways in trophoblasts［J］.Front Immunol，2021，12： 743700. |
| 17 | Cheng SB， Nakashima A， Huber WJ， et al. Pyroptosis is a critical inflammatory pathway in the placenta from early onset preeclampsia and in human trophoblasts exposed to hypoxia and endoplasmic reticulum stressors［J］.Cell Death Dis，2019，10（12）： 927. |
| 18 | Pereira MM， Torrado J， Sosa C， et al. Shedding light on the pathophysiology of preeclampsia-syndrome in the era of cardio-obstetrics： role of inflammation and endothelial dysfunction［J］.Curr Hypertens Rev，2022，18（1）： 17. |
| 19 | Nieto-Orellana A， Li H， Rosiere R， et al. Targeted PEG-poly （glutamic acid） complexes for inhalation protein delivery to the lung［J］.J Control Release，2019，316： 250. |
| 20 | Tuli HS， Kaur J， Vashishth K， et al. Molecular mechanisms behind ROS regulation in cancer： a balancing act between augmented tumorigenesis and cell apoptosis［J］.Arch Toxicol，2023，97（1）： 103. |
| 21 | Zhang YJ， Lu Y， Jin LP. Iron metabolism and ferroptosis in physiological and pathological pregnancy［J］.Int J Mol Sci，2022，23（16）： 9395. |
| 22 | Garcia-Casal MN， Pasricha SR， Martinez RX， et al. Serum or plasma ferritin concentration as an index of iron deficiency and overload［J］.Cochrane Database Syst Rev，2021，5（5）： Cd011817. |
| 23 | Mégier C， Peoc'h K， Puy V， et al. Iron metabolism in normal and pathological pregnancies and fetal consequences［J］.Metabolites，2022，12（2）： 129. |
| 24 | Gong XL， Li JX， Jiang YH， et al. Risk of preeclampsia by gestational weight gain in women with varied prepregnancy BMI： a retrospective cohort study［J］.Front Endocrinol （Lausanne），2022，13： 967102. |
| 25 | Ng SW， Norwitz SG， Norwitz ER. The impact of iron overload and ferroptosis on reproductive disorders in humans： implications for preeclampsia［J］.Int J Mol Sci，2019，20（13）： 3283. |
| 26 | Chen HJ， Sugiyama M， Shimokawa F， et al. Response to iron overload in cultured hepatocytes［J］.Sci Rep，2020，10（1）： 21184. |
| 27 | Botero JP， McIntosh JJ. Labor and delivery： DIC， HELLP， preeclampsia［J］.Hematology Am Soc Hematol Educ Program，2023，2023（1）： 737. |
| 28 | Liao TT， Xu X， Ye X， et al. DJ-1 upregulates the Nrf2/GPX4 signal pathway to inhibit trophoblast ferroptosis in the pathogenesis of preeclampsia［J］.Sci Rep，2022，12（1）： 2934. |
| 29 | Hodyl NA， Aboustate N， Bianco-Miotto T， et al. Child neurodevelopmental outcomes following preterm and term birth： what can the placenta tell us？［J］.Placenta，2017，57： 79. |
| 30 | Rana S， Lemoine E， Granger JP， et al. Preeclampsia： pathophysiology， challenges， and perspectives［J］.Circ Res，2019，124（7）： 1094. |
| 31 | Staff AC. The two-stage placental model of preeclampsia： an update［J］.J Reprod Immunol，2019，134/135： 1. |
| 32 | Rottenstreich A， Arad A， Terespolsky H， et al. Antiphospholipid antibody profile-based outcome of purely vascular and purely obstetric antiphospholipid syndrome［J］.J Thromb Thrombolysis，2018，46（2）： 166. |
| 33 | Kraft VAN， Bezjian CT， Pfeiffer S， et al. GTP cyclohydrolase 1/tetrahydrobiopterin counteract ferroptosis through lipid remodeling［J］.ACS Cent Sci，2020，6（1）： 41. |
| 34 | Jauniaux E， Burton GJ. The role of oxidative stress in placental-related diseases of pregnancy［J］.J Gynecol Obstet Biol Reprod （Paris），2016，45（8）： 775. |
| 35 | Brown MA， Magee LA， Kenny LC， et al. Hypertensive disorders of pregnancy： ISSHP classification， diagnosis， and management recommendations for international practice［J］.Hypertension，2018，72（1）： 24. |
| 36 | Gaschler MM， Stockwell BR. Lipid peroxidation in cell death［J］.Biochem Biophys Res Commun，2017，482（3）： 419. |
| 37 | Kruk J， Aboul-Enein HY， K?adna A， et al. Oxidative stress in biological systems and its relation with pathophysiological functions： the effect of physical activity on cellular redox homeostasis［J］.Free Radic Res，2019，53（5）： 497. |
| 38 | El-Khalik SRA， Ibrahim RR， Ghafar MTA， et al. Novel insights into the SLC7A11-mediated ferroptosis signaling pathways in preeclampsia patients： identifying pannexin 1 and toll-like receptor 4 as innovative prospective diagnostic biomarkers［J］.J Assist Reprod Genet，2022，39（5）： 1115. |
| 39 | Melchiorre K， Giorgione V， Thilaganathan B. The placenta and preeclampsia： villain or victim？［J］.Am J Obstet Gynecol，2022，226（2S）： S954. |
| 40 | Shaji Geetha N， Bobby Z， Dorairajan G， et al. Increased hepcidin levels in preeclampsia： a protective mechanism against iron overload mediated oxidative stress？［J］.J Matern Fetal Neonatal Med，2022，35（4）： 636. |
| 41 | Chen ZX， Gan JF， Zhang M， et al. Ferroptosis and its emerging role in pre-eclampsia［J］.Antioxidants （Basel），2022，11（7）： 1282. |
| 42 | Redman CW， Sacks GP， Sargent IL. Preeclampsia： an excessive maternal inflammatory response to pregnancy［J］.Am J Obstet Gynecol，1999，180（2 Pt 1）： 499. |
| 43 | Wang Y， Li BX， Zhao Y. Inflammation in preeclampsia： genetic biomarkers， mechanisms， and therapeutic strategies［J］.Front Immunol，2022，13： 883404. |
| 44 | Staff AC， Johnsen GM， Dechend R， et al. Preeclampsia and uteroplacental acute atherosis： immune and inflammatory factors［J］.J Reprod Immunol，2014，101/102： 120. |
| 45 | Cornelius DC， Wallace K. Decidual natural killer cells： a critical pregnancy mediator altered in preeclampsia［J］.EBioMedicine，2019，39： 31. |
| 46 | Hiby SE， Apps R， Chazara O， et al. Maternal KIR in combination with paternal HLA-C2 regulate human birth weight［J］.J Immunol，2014，192（11）： 5069. |
| 47 | Nakimuli A， Chazara O， Hiby SE， et al. A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia［J］.Proc Natl Acad Sci U S A，2015，112（3）： 845. |
| 48 | Tsuda S， Zhang XX， Hamana H， et al. Clonally expanded decidual effector regulatory T cells increase in late gestation of normal pregnancy， but not in preeclampsia， in humans［J］.Front Immunol，2018，9： 1934. |
| 49 | Hosseini A， Dolati S， Hashemi V， et al. Regulatory T and T helper 17 cells： their roles in preeclampsia［J］.J Cell Physiol，2018，233（9）： 6561. |
| 50 | Miller D， Motomura K， Galaz J， et al. Cellular immune responses in the pathophysiology of preeclampsia［J］.J Leukoc Biol，2022，111（1）： 237. |
| 51 | Dixon SJ， Lemberg KM， Lamprecht MR， et al. Ferroptosis： an iron-dependent form of nonapoptotic cell death［J］.Cell，2012，149（5）： 1060. |
| 52 | Zheng QQ， Zhao YS， Guo J， et al. Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome［J］.Leuk Res，2017，58： 55. |
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