The role of cytokines in reprodution and embryogenesis

细胞因子在生殖和胚胎发生中的作用

• 批准号: 05304039
• 负责人: MORI Takahide
• 金额: $ 9.79万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Co-operative Research (A)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05304039/
• 关键词: Gonadal steroids; Cytokine; mRNA; Pituitary; Ovary; endometrium; placenta; trophoblast; 絨毛膜細胞

To clarify the role of cytokines in regulation of gonadotropin secretion, rat anterior pituitary cells were cultured with various cytokines and FSH levels in the culture supernatants were examined .Activin A showed a significant enhancement on the secretion of FSH,and mRNA for activin A was identified in rat ovarian follicles and placenta.FSH secretion was also enhanced by insulin-like growth factor.In the culture of porcine granulosa cells, IL-1, TNFalpha and IFNgamma showed a significant suppressive effect on steriodogenesis.But lymphocytes can stimulates the progesterone production by granulosa luteal cells, suggesting the complex effect of cytokines on follicular cells at different developmental stages.In the corpus luteum, macrophages inhibited 17beta-dehydroxylase activity and maintain the high local progesterone levels.During luteolysis, mRNA for cytokines of CSF and TGFbeta was detected by subtraction suggesting that these cytokines from local macrophages have a role in luteal … More cell regression.In endometrium, cytokines have important roles in the proliferation/differentiation of not only local immune cells but also endometrial cells.IL-1.and TNFalpha inhibited a process of endometrial stromal cell differentiation induced by progesterone(decidualization), and endometrial cells can produce cytokines of M-CSF,SCF,LIF,IL-6 and TGFbeta.The production of M-CSF and TGFbeta by stromal cells was regulated by gonadal steroids.In placenta, receptors for M-CSF,IL-6 and LIF were identified and the addtion of these cytokines to early pregnancy placental trophoblasts or trophoblastic cell lines showed the enhancing or inhibiting effect of these cytokines on trophoblast cell proliferation and hCG secretion.Therefore it is suggested that the cytokines produced in the uterine endometrium under the control of ovarian gonagdal steroids have roles in plascental growth and differentiation.In addition, M-CSF had growth promoting effect on pre-implantation mouse embryo.In addition to these cytokines, a novel molecule of midkine(MK)found as a product of a retinoic acid-responsive gene has an important roles in embryogenesis.The receptor for MK was analyzed and its role in placental/fetal development is intensively examined. Less

为了阐明细胞因子在调节促性腺激素分泌中的作用，用各种细胞因子培养大鼠垂体前叶细胞，并检测培养物上清液中的FSH水平。激活素A显示出对FSH分泌的显着增强，并且在大鼠卵泡和胎盘中鉴定出激活素A的mRNA。胰岛素样生长因子也增强FSH分泌。 猪颗粒细胞、IL-1、TNFα和IFNγ对类固醇生成有显着的抑制作用。但淋巴细胞可以刺激颗粒黄体细胞产生黄体酮，提示细胞因子对不同发育阶段的滤泡细胞的复杂作用。在黄体中，巨噬细胞抑制17β-脱羟酶 活性并维持较高的局部黄体酮水平。在黄体溶解过程中，通过减法检测到 CSF 和 TGFbeta 细胞因子的 mRNA，表明这些来自局部巨噬细胞的细胞因子在黄体细胞退化中发挥作用。在子宫内膜中，细胞因子不仅在局部免疫细胞而且在子宫内膜细胞的增殖/分化中发挥重要作用。IL-1. 和 TNFα 抑制黄体酮诱导的子宫内膜基质细胞分化过程（蜕膜化），子宫内膜细胞可产生M-CSF、SCF、LIF、IL-6和TGFbeta细胞因子。基质细胞产生M-CSF和TGFbeta受性腺类固醇调节。在胎盘中，鉴定了M-CSF、IL-6和LIF受体，并确定了M-CSF、IL-6和LIF受体。 将这些细胞因子添加到早孕胎盘滋养层或滋养层细胞系中，显示这些细胞因子对滋养层细胞增殖和hCG分泌有增强或抑制作用。因此，提示在卵巢性腺类固醇控制下的子宫内膜中产生的细胞因子对胎盘生长和分化有作用。 M-CSF对植入前小鼠胚胎具有促进生长的作用。除了这些细胞因子外，作为视黄酸反应基因产物而发现的新型中期因子(MK)分子在胚胎发生中具有重要作用。对MK受体进行了分析，并深入研究了其在胎盘/胎儿发育中的作用。较少的

项目成果

Mitsiadis, T.A., Salmivirta, M., Muramatsu, T., Muramatsu, H., Rauvala, H., Lehtonen, E.and Theslef, I.: "Expression of the heparin-binding cytokines, midkine(MK)and HB-GAM(pleiotrophin)is associated with epithelial-mesenchymal interactions during fetal d

Mitsiadis, T.A.、Salmivirta, M.、Muramatsu, T.、Muramatsu, H.、Rauvala, H.、Lehtonen, E. 和 Theslef, I.：“肝素结合细胞因子、中期因子 (MK) 和 HB- 的表达

Muramatsu, H., Inui, T., Kimura, T., Sakakibara, S., Song, X., Murata, H.and Muramatsu, T: "Localization of heparin-binding, neurite outgrowth and antigenic regions in midkine molecule" Biochem.Biophys.Res.Commun. 203. 1131-1139 (1994)

Muramatsu, H.、Inui, T.、Kimura, T.、Sakakibara, S.、Song, X.、Murata, H.和 Muramatsu, T：“中期因子分子中肝素结合、神经突生长和抗原区域的定位”

Inoue, T., Kanzaki, H., Iwai, M., Imai, K., Narukawa, S., Higuchi, T., Katsuragawa, H.and Mori, T.: "Tumor necrosis factor alpha(TNFalpha)inhibits in-vitro decidualization of human endometrial stromal cells." Human Reproduction. 9. 2411-2417 (1994)

Inoue, T.、Kanzaki, H.、Iwai, M.、Imai, K.、Narukawa, S.、Higuchi, T.、Katsurakawa, H. 和 Mori, T.：“肿瘤坏死因子 α (TNFα) 抑制

Horibe, N., Okamoto, T., Itakura, A., Nakanishi, T., Suzuki, T., Kazeto, S.and Tomoda, Y.: "Levels of hepatocyte growth factor in maternal serum and in amniotic fluid." Am J Obstet Gynecol. (in press). (1995)

Horibe, N.、Okamoto, T.、Itakura, A.、Nakanishi, T.、Suzuki, T.、Kazeto, S.和 Tomoda, Y.：“母体血清和羊水中的肝细胞生长因子水平。”

M.Take,et al.: "Identification of nucleolin as a binding protein for midkine (MK) and heparin-binding growth-associated molecule(HB-GAM)" J.Biochem.116. 1063-1068 (1994)

M.Take 等人：“核仁素作为中期因子 (MK) 和肝素结合生长相关分子 (HB-GAM) 结合蛋白的鉴定”J.Biochem.116。