The role of cytokines in reprodution and embryogenesis

为了阐明细胞因子在促性腺激素分泌调节中的作用，用不同的细胞因子培养大鼠垂体前叶细胞，检测培养上清液中的FSH水平。激活素A显著促进FSH的分泌，激活素A在大鼠卵泡和胎盘中检测到激活素A的mRNA。胰岛素样生长因子也促进FSH的分泌。在猪颗粒细胞培养中，IL-1、TNFα和IFNγ对性激素的生成有明显的抑制作用。但淋巴细胞可以刺激黄体颗粒细胞孕酮的产生，提示细胞因子对不同发育阶段的卵泡细胞的作用是复杂的。在黄体中，巨噬细胞抑制17β-脱羟酶活性，维持黄体局部较高的孕酮水平。在黄体溶解过程中，用差减方法检测到脑脊液细胞因子和转化生长因子β基因的表达，提示局部巨噬细胞产生的这些细胞因子在黄体…中起作用更多的细胞退化。在子宫内膜中，细胞因子不仅在局部免疫细胞的增殖/分化中起重要作用，而且在子宫内膜细胞的增殖/分化中起重要作用。IL-1和TNFα抑制孕酮诱导的子宫内膜间质细胞分化过程，子宫内膜细胞可以产生M-CSF、SCF、LIF、IL-6和TGFβ等细胞因子。间质细胞产生M-CSF和TGFβ受性腺激素的调节。在胎盘中，M-CSF的受体，IL-6和LIF在早孕胎盘滋养层细胞或滋养层细胞系中的作用表明，这些细胞因子对滋养层细胞的增殖和hCG的分泌有促进或抑制的作用。因此，我们认为子宫内膜在卵巢性激素的调控下产生的细胞因子对胞质的生长和分化有一定的作用。此外，M-CSF对小鼠着床前胚胎有生长促进作用。除了这些细胞因子外，M-CSF还可以促进小鼠胚胎的生长。一种新的中期因子分子(MK)是维甲酸反应基因的产物，在胚胎发育中起着重要的作用。较少

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