Modric T, Kowalski A A, Green M L, Simmen R C, Simmen F A
Department of Physiological Sciences, University of Florida, Gainesville, Florida, 32611-0920, USA.
Placenta. 2000 May;21(4):345-53. doi: 10.1053/plac.1999.0493.
Leukaemia inhibitory factor (LIF) and interleukin-6 (IL-6) are candidate embryo-maternal signalling molecules which are present within the uterine luminal micro-environment. We examined the relative expression of the mRNAs encoding LIF and IL-6, as well as the LIF-binding subunit (LIFR-beta) of the LIF receptor and, as a potential downstream cytokine-responsive gene, beta(2)-microglobulin (beta(2)m), in porcine peri-implantation conceptuses, and in placenta and endometrium during early and mid-pregnancy. Peri-implantation spherical and filamentous conceptuses expressed LIFR-beta and beta(2)m mRNAs with no LIF mRNA present. Rapid development in days 11/12 spherical conceptuses to the filamentous stage was accompanied by transiently increased IL-6 gene expression. The corresponding endometrium, in contrast, expressed LIF in addition to these other mRNAs. LIFR-beta, IL-6 and beta(2)m, but not LIF mRNAs, were expressed in the Jag-1 cell line, an in vitro model for porcine day 14 trophoblast. The greatest steady-state amounts of LIF, LIFR-beta and IL-6 mRNAs in both the endometrium and placenta were evident at the post-implantation stages (days 30 and 60>day 18 of pregnancy). Treatment of porcine endometrial explants with human recombinant (hr)LIF or hrIL-6 resulted in no change in, or diminished, the presence of endometrial beta(2)m mRNA, respectively. Addition of LIF to peri-implantation conceptus explant cultures, in contrast, induced beta(2)m mRNA synthesis. These results highlight the potential importance of both the endometrium and placenta as sources, as well as targets, of these cytokines throughout pregnancy. Cytokine modulation of beta(2)m, a known in vitro mitogen, may constitute one mechanism for local control of trophoblast and endometrial proliferation.
白血病抑制因子(LIF)和白细胞介素-6(IL-6)是子宫腔微环境中存在的胚胎-母体信号分子候选物。我们检测了编码LIF和IL-6的mRNA的相对表达,以及LIF受体的LIF结合亚基(LIFR-β),并且作为潜在的下游细胞因子反应性基因,检测了猪着床前后的孕体、妊娠早期和中期胎盘及子宫内膜中β2-微球蛋白(β2m)的表达。着床前后的球形和丝状孕体表达LIFR-β和β2m的mRNA,但不存在LIF mRNA。在第11/12天球形孕体快速发育至丝状阶段的过程中,IL-6基因表达短暂增加。相比之下,相应的子宫内膜除了表达这些其他mRNA外,还表达LIF。LIFR-β、IL-6和β2m的mRNA在Jag-1细胞系中表达,但LIF的mRNA不表达,Jag-1细胞系是猪第14天滋养层的体外模型。在着床后阶段(妊娠第30天和60天>第18天),子宫内膜和胎盘中LIF、LIFR-β和IL-6的mRNA的稳态量最高。用人重组(hr)LIF或hrIL-6处理猪子宫内膜外植体,分别导致子宫内膜β2m的mRNA含量无变化或减少。相比之下,向着床前后的孕体外植体培养物中添加LIF可诱导β2m的mRNA合成。这些结果突出了子宫内膜和胎盘作为这些细胞因子在整个妊娠期间的来源和靶点的潜在重要性。细胞因子对β2m(一种已知的体外有丝分裂原)的调节可能构成局部控制滋养层和子宫内膜增殖的一种机制。