{"title":"The role of leukemia inhibitory factor in regulating angiogenesis-related gene expression in a mouse model of recurrent miscarriage","authors":"Zahra Allahyari , Narges Nikoonahad Lotfabadi , Fateme Zare","doi":"10.1016/j.placenta.2025.04.009","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Recurrent miscarriage is an early pregnancy complication that affects approximately 1–3 % of pregnant couples. Leukemia Inhibitory Factor (LIF) plays an important role in various biological processes, including angiogenesis and pregnancy. This study aimed to evaluate the role of LIF in regulating angiogenesis-related genes in a mouse model of recurrent miscarriage.</div></div><div><h3>Method</h3><div>Female CBA/J mice mated with DBA/2J males were utilized as a miscarriage model. The study population was randomly assigned to three groups, normal group, mating female CBA/J mouse with male Balb/c without injection; miscarriage model control group with PBS injection; and the miscarriage group, in which LIF was injected. Following detection of a vaginal plug, mice were dissected on days 4, 7, and 14 of pregnancy. Uterine and placental tissues were collected to assess the expression of angiogenesis-related genes, including VEGF, PDGF, ANG1, FGF, and TGF-β, using real-time PCR.</div></div><div><h3>Result</h3><div>Data analysis revealed no significant differences in the expression of angiogenesis-related genes on days 4 and 7 of pregnancy compared with the control group. However, on day 14 of pregnancy, the expression of VEGF and TGF-β was significantly elevated in the miscarriage group receiving LIF compared to other groups (P = 0.03 and P = 0.04, respectively). The placental expression of the studied genes also exhibited a non-significant increase in the miscarriage group, with VEGF and TGF-β showing the most prominent increases, although these changes were not statistically significant. Correlation analysis between uterine and placental gene expression on day 14 revealed no significant association.</div></div><div><h3>Conclusion</h3><div>LIF regulates the uterine and placental expression of angiogenesis-related genes, particularly VEGF and TGF-β. These findings highlight the role of LIF in regulating angiogenesis-related gene expression and suggest that LIF could be a potential therapeutic candidate for improving pregnancy outcomes in cases of recurrent miscarriage.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"165 ","pages":"Pages 91-101"},"PeriodicalIF":2.5000,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Placenta","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0143400425001110","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Recurrent miscarriage is an early pregnancy complication that affects approximately 1–3 % of pregnant couples. Leukemia Inhibitory Factor (LIF) plays an important role in various biological processes, including angiogenesis and pregnancy. This study aimed to evaluate the role of LIF in regulating angiogenesis-related genes in a mouse model of recurrent miscarriage.
Method
Female CBA/J mice mated with DBA/2J males were utilized as a miscarriage model. The study population was randomly assigned to three groups, normal group, mating female CBA/J mouse with male Balb/c without injection; miscarriage model control group with PBS injection; and the miscarriage group, in which LIF was injected. Following detection of a vaginal plug, mice were dissected on days 4, 7, and 14 of pregnancy. Uterine and placental tissues were collected to assess the expression of angiogenesis-related genes, including VEGF, PDGF, ANG1, FGF, and TGF-β, using real-time PCR.
Result
Data analysis revealed no significant differences in the expression of angiogenesis-related genes on days 4 and 7 of pregnancy compared with the control group. However, on day 14 of pregnancy, the expression of VEGF and TGF-β was significantly elevated in the miscarriage group receiving LIF compared to other groups (P = 0.03 and P = 0.04, respectively). The placental expression of the studied genes also exhibited a non-significant increase in the miscarriage group, with VEGF and TGF-β showing the most prominent increases, although these changes were not statistically significant. Correlation analysis between uterine and placental gene expression on day 14 revealed no significant association.
Conclusion
LIF regulates the uterine and placental expression of angiogenesis-related genes, particularly VEGF and TGF-β. These findings highlight the role of LIF in regulating angiogenesis-related gene expression and suggest that LIF could be a potential therapeutic candidate for improving pregnancy outcomes in cases of recurrent miscarriage.
期刊介绍：
Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
