摘要
目的
利用免疫组织化学及图像分析技术，定位在胎儿生长受限(FGR)和正常足月胎盘组织中的白血病抑制因子(LIF)及瘦素(Leptin)，探讨它们的相关性及与胎儿生长发育的关系。
方法
取人正常足月分娩胎盘与胎儿生长受限胎盘各15例，行常规HE染色对胎盘组织行形态学研究，借助免疫组化SP法及图像分析技术定量分析各例胎盘组织中LIF及Leptin在绒毛滋养层的的表达。
结果
1．与正常妊娠组胎盘比较，FGR组胎盘绒毛发育欠佳，绒毛血管扩张不良，细胞滋养细胞增生，血管合体膜增厚。
2．LIF主要表达于绒毛滋养细胞和血管内皮细胞胞浆中；Leptin主要表达于胎盘合体滋养层细胞的胞浆中。
Purpose
To study the expression and the localization of leukemia inhibitory factor (LIF) and leptin in placenta from normal pregnancy and fetal growth restriction (FGR).
Methods
Placental samples obtained from 30 women were divided into 2 groups, FGR group (n=15) and control group (n=15). Tissue samples were fixed in formalin, embedded in paraffin and processed for routine histological examination and immunohistochemical identification of LIF and Leptin expression.
Results
1.FGR tissue sections compared with control group, showed a poor development on placental villus, villous capillaries were not dilated, hyperplasia of the cytotrophoblasts increased the thickness of vasculosyncytial membrane.
2.LIF mainly expressed in placenta villous trophoblasts and fetal vasular endothelium; Leptin expressed on the placenta villous syncytiotrophoblast.
引文
1．曹泽毅，主编．中华妇产科学[M]．上册．第二版．北京：人民卫生出版社，2004．
2. Wang X, Athayde N, Trudinger B. Maternal plasma from pregnant women with umbilical placental vascular disease does not affect endothelial cell mRNA expression of nitric oxide synthase[J]. J Soc Gynecol Invest,2004,11(3):149-153.
3．尹利荣，马鸿达，王欣，等．不明原因胎儿宫内发育迟缓胎盘床和胎盘血管病变的探讨[J]．天津医药，1998，26(11)：643-645．
4. Senturk LM, Arici A. Leukemia inhibitory factor in human reproduction [J]. Am J Reprod Immunol, 1998,39:144-151.
5. Hisaka T, Desmouliere A, Taupin JL, et al. Expression of leukemia inhibitory factor (LIF) and its receptor gpl90 in human liver and in cultured human liver myofibroblasts. Cloning of new isoforms of LIF mRNA[J]. Comp Hepatol, 2004,3:10.
6. Hilon DJ, Nicola NA, Waring PM, et al. Leukemia inhibitory factor[J]. J Biochem,1998,273(22):13735-13745.
7. Hambartsoumian E. Endometrial leukemia inhibitory factor (LIF) as a possible cause of unexplained infertility and multiple failures of implantation[J]. Am J Reprod Immunol, 1998,39(2): 137-143.
8. Arici A, Oral E, Bahliyar O, et al. Leukemia inhibitory factor expression in human follicular fluid and ovarian cells[J]. Hum Repro, 1997,12:1233-1239.
9. Jean M, Mensier A, Godard A, et al. Leukemia inhibitory factor cconcentration in follicular fluid: A marker of oocyte quality[J]? Hum Reprod,1997,12:145
10. Dunglison GF, Barlow DH, Sargent IL. Leukemia inhibitory factor Significantly enhance the blastocyst formation rates of human embryos cultured in serum-free medium[J]. Hum Reprod, 1996,11:191-196.
11. Nachtigall MJ, Klimayn HJ, Feinberg RF, et al. The effect of Leukemia inhibitory factor (LIF) on trophoblast differentiation: Apotential role in human implantation[J]. J Clin Endocrinol Metab, 1996,81: 801-806.
12. Chaouat G, Menu E, Delage G, et al. Immuno-endocrine interactions in early pregnancy[J]. Hum Reprod, 1995,10(suppl 2):55-59.
13. Sawai K, Matsuzaki N, Kameda T, et al. Leukemia inhibitory factor produced at fetomaternal interface stimulates chorionic gonadotropin production: its possible implication during pregnancy, including implantation period[J]. J Clin Endocrinol Metab, 1995,80:1449-1456.
14. Davis S, Aldrich TH, Stahl N, et al. LIFR and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor[J]. Science,1993,260:1805-1808.
15. Yoshida CL, Taga T, Saito M, et al. Targeted disruption of gp 130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders[J]. Proc Natl Acad Sci USA, 1996,93:407-410.
16. Stewart CL. The role of leukemia inhibitory factor (LIF) and other cytokines in regulating implantation in mammals[J]. Ann NY Acad Sci,1994,734:157-165.
17. Vasse M, Pourtau J, Trochon V, et al. Oncostatin M induces angiogenesis in vitro and in vivo[J]. Arterioscler Thromb Vasc Biol, 1999, 19(8): 1835-1842.
18. Pepper MS, Ferrara N, Orci L, et al. Leukaemia inhibitory factor (LIF) inhibits angiogenesis in vitro[J]. J Cell Sci,1995,108:73-83.
19. Ferrara N, Winer J, Henzel WJ. Pituitary follicular cells secrete an inhibitor of aortic endothelial cell growth: identification as leukaemia inhibitory factor[J]. Proc Natl Acad Sci U S A, 1992,89:698-702.
20. Gendron RL, Tsai FY, Paradis H, et al.Induction of embryonic vasculogenesis by bFGF and LIF in vitro and in vivo[J]. Developmental Biology,1996,177:332-346.
21. Kimura K, Tsuda K, Moriwaki C, et al. Leukemia inhibitory factor relaxes arteries through endothelium-dependent mechanism[J]. Biochem Biophys Res Commun,2002,294(2):359-362.
22. Moran CS, Campbell JH, Simmons DL, et al. Human leukemia inhibitory factor inhibits development of experimental atherosclerosis[J]. Arterioscler Thromb Vasc Biol,1994,14:1356-1363.
23. Zhang YY, Proeoce R, Maffer M, et al. Positional cloning of the mouse obese gene and its human homologue[J]. Nature, 1994,372:425-431.
24. Stephens T, Basinski M, Bristow P, et al. The role of neuropeptide Y in the antiobesity action of the obese gene product[J]. Nature,1995,377(4):530-532.
25. Chehab FF, Mounzih K, Lu R, et al. Early onset of reproduction function in normal female mice treated with leptin[J]. Science,1997,275:88-91.
26. Bouloumie A, Drexler HC, Lafontan M, et al. Leptin, the product of ob gene, premotes angiogenesis[J]. Circ Res, 1998,86:1059-1066.
27. Funahashi H, Yada T, Suzuki R, et al. Distribution, function, and properties of leptin receptors in the brain[J]. Int Rev Cytol,2003,224:1-27.
28. Bjorhaek C, Kahn BB. Leptin signaling in the central nervous system and the periphery[J]. Recent Prog Horm Res,2004,7(2):305-331.
29. Muoio DM, Lynis Dohm G Peripheral metabolic actions of leptin[J]. Best Pract Res Clin Endocrinol Metab,2002,16(4):653-666.
30. Harris RB. Leptin-much more than a satiety signal[J]. Annu Rev Nutr, 2000, 20(1):45-75.
31. Tartaglia L. The leptin receptor[J]. J Biol Chem, 1997,272:6093-6096.
32. Lea RG Howe D, Hannah LT, et al. Placental leptin in normal, diabetic and fetal growth-retarded pregnancies[J]. Mol Hum Reprod,2000,6(8):763-769.
33. Tamura T, Goldenberg RL, Johnson KE, et al. Serum leptin concentrations during pregnancy and their relationship to fetal growth[J]. Obstet gynecol,1998, 91(2):389-395.
34. Linnemann K, Malice A, Sager R, et al. Leptin production and release in the dually in vitro perfused human placenta[J]. J Clin Endocrinol Metal, 2000,85: 4298-4301.
35. Masuzaki H, Ogawa Y, Sagawa N, et al. Nonadipose tissue production of leptin: leptin as a novel placeta-derived hormone in humans[J]. NatMed, 1997,3: 1029-1033.
36. Hardie L, Trayhum P, Abramovich D, et al. Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy [J]. Clin Endocrinol, 1997,47:101 -106.
37. Jaquet ET, Leger J, Levy-Marchal C, et al. Ontogeny of leptin in human fetuses and newborns:effect of intrauterine growth retardation on serum leptin concentrations[J]. J Clin Endocrinol Metab, 1998,83:1243-1246.
38. Gomez L, Carrascosa A, Yeste D, et al. Leptin values in placental cord blood of human newborns with normal intrauterine growth after 30-42 weeks of gestation[J]. Horm Res, 1999,51:10-14.
39. Rogol AD. Leptin and puberty[J]. J Clin Endocrinol Metab, 1998,83(4): 1089-1090.
40. Jaquet D, Leger J, Levy-marchal C, et al. Ontogeny of leptin in human fetuses and newborns: Effect of intrauterine growth retardation on serum leptin concentrations[J]. J Clin Endocrinal Metab, 1998,83:1243-1246.
41. Leperco J, Challier JC, Michelle GM, et al. Placental leptin production: evidence that fetal adipode tissue produces leptin[J]. J Clin Endocrinol Metab,2001,86(6): 2409-2414.
42. Yura S, Sagawa N, Mori T, et al. Positive umbilical venous-arterial difference of lepin level and its rapid decline after birth[J]. Am J Obstet Genecol,1998,178(5): 726-730.
43. Ghilardi N, Ziegler S, Wiestner A, et al. Defective STAT signaling by the leptin receptor in diabetic mice[J]. Proc Natl Acad Sci USA, 1996,93:6231-6235.
44. Zabeau L, Lavens D, Peelman F, et al. The ins and outs of leptin receptor activation[J]. FEBS Lett,2003,546:45-50.
45. Cheng JG, Chen JR, Hernandez L, et al. Dual control of LIF expression and LIF receptor function regulate Stat3 activation at the onset of uterine receptivity and embryo implantation[J]. Proc Natl Acad Sci USA,2001,98:8680-8685.
46. Takahashi Y, Okimura Y, Mizuno I, et al. Leptin induces mitogen-activated protein kinase-dependent proliferation of C3H 10T1/2 cells[J]. J Biol Chem, 1997,272:12897-12900.
47. Gonzalez RR, Leavis P. Leptin upregulates β3-integrin expression and interleukin-1β, upregulates leptin and leptin receptor expression in human endometrial epithelial cell cultures. Endocrine,2001,16:21-28.
48. Takahashi Y, Carpino N, Cross JC, et al. SOCS3: an essential regulator of LIF receptor signaling in trophoblast giant cell differentiation[J]. EMBO J,2003,22: 372-384.
49. Bjorbak C, Lavery HJ, Bates SH, et al. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985[J]. J Biol Chem,2000,275:40649-40657.
50. Fedorcsak P, Storeng R. Effects of leptin and leukemia inhibitory factor on preimplantation development and STAT3 signaling of mouse embryos in vitro[J]. Biol Reprod,2003,69:1531-1538.
51. Gonzalez RR, Rueda BR, Ramos MP, et al. Leptin-Induced Increase in Leukemia Inhibitory Factor and Its Receptor by Human Endometrium Is Partially Mediated by Interleukin 1 Receptor Signaling[J]. Endocrinology,2004,145(8):3850-3857.
52．申洪．免疫组织化学染色定量方法研究(Ⅲ)．中国组织化学与细胞化学杂志，1995，4(1)：89-90．
53. Stewart CL, Kaspar P, Brunet LJ, et al. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor[J]. Nature, 1992,359:76-79.
54. Chen JR, Cheng JG, Shatzer T, et al. Leukemia inhibitory factor can substitute for nidatory estrogen and is essential to inducing a receptive uterus for implantation but is not essential for subsequent embryogenesis[J]. Endocrinol, 2000,141:4365-4372.
55. Ware CB, Horowitz MC, Renshaw BR, et al. Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death[J]. Development,1995, 121:1283-1299.
56. Li M, Sendtner M, Smith A. Essential function of LIF receptor in motor neurons[J]. Nature, 1995,378:724-727.
57. Sharkey AM, King A, Clark DE, et al. Localization of leukemia inhibitory factor and its receptor in human placenta throughout pregnancy[J]. Biol Reprod, 1999,60:355-364.
58. Kayisli UA, Selam B, Demir A, et al. Expression of vasodilatator-stimulated phosphoprotein in human placenta Possible implications in trophoblast invasion[J]. Mol Hum Reprod,2002,8:88-94.
59. Poehlmann TG, Fitzgerald JS, Meissner A, et al. Trophoblast invasion: tuning through LIF, signalling via Stat3 [J]. Placenta,2005,26(1):S37-S41.
60．孔英，葛常辉，燕秋，等．白血病抑制因子对胚泡金属蛋白酶表达的影响[J]．生物化学与生物物理进展，2002，29(2)：278-282．
61. Suzuki S, Tanaka K, Nogawa S, et al.Immunohistochemical detection of leukemia inhibitory factor after focal cerebral ischemia in rats[J].J Cereb Blood Flow Metab,2000,20(4):661-668.
62. Suzuki S, Yamashita T, Tanaka K, et al. Activation of cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 attenuates ischemic brain injury in rats[J]. J Cereb Blood Flow Metab,2005,25:685-693.
63. Zou Y, Takano H, Mizukami M, et al. Leukemia inhibitory factor enhances survival of cardiomyocytes and induces regeneration of myocardium after myocardial infarction[J]. Circulation,2003,108(6):748-753.
64. van der Veen F, Fox H. The human placenta in idiopathic intrauterine growth retardation: a light and electron microscopic study[J]. Placenta, 1983,4(1):65-77.
65. Hassink SG, de Lancey E, Sheslow DV, et al. Placental leptin: an important new growth factor in intrauterine and neonatal development[J]? Pediatrics,1997, 100:124(abstE1).
66. Lin KC, Hsu SC, Kuo CH, et al. Difference of plasma leptin levels in venous and arterial cord blood: relation to neonatal and placental weight. Kaohsiung J Med Sci, 1999,15:679-685.
67．高云，朱绍敏，高红，等．孕妇血清瘦素水平及对孕期和产后体重的影响[J]．中国优生与遗传杂志，2001，9(1)：67-68．
68. Wiznitzer A, Furm an B, Zuili I, et al. Cord leptin level and fetal macrosomia[J]. Obstet Gyecol,2000,96(11):707-713.
69．匡军秀，曹来英，周小玲，等．妊娠期高血压疾病患者胎盘瘦素的表达及意义[J]．中国实用妇科与产科杂志，2004，20(12)：749-750．
70. Mise H, Sagawa N, Matsumoto T, et al. Augmented placental production of leptin in preeclampsia: possible involvement of placental hypoxia. J Clin Endocrinol Metab, 1998,83(9):3225-3229.