Mathialagan N, Roberts R M
Department of Animal Sciences, University of Missouri-Columbia 65211.
Indian J Physiol Pharmacol. 1994 Jul;38(3):153-62.
Cytokines are expressed in a variety of cell types of the reproductive system, although in most instances their functions are not understood. There are, however, a few instances where a role in early pregnancy has been established. First, preimplantation conceptuses of ruminant ungulate species, such as cattle, sheep and goat, secrete a unique Type I interferon (IFN-tau). By mechanisms that are still unclear, IFN-tau prevents the destruction of the corpus luteum and hence ensures the continued production of progesterone which is essential for continuation of pregnancy. Most like the IFN-tau prevent lutcolysis by modulating the output of a luteolytic hormone, prostaglandin F2 alpha, from the uterus. Depsite this involvement in pregnancy, the IFN-tau possess similar antiproliferative and antiviral activities to other Type I IFN, 1 lambda e.g. IFN-alpha. There are 4-5 genes for IFN-tau in sheep and cattle whose promotor regions are highly conserved and distinct from those of other Type I IFN. These genens are not virally inducible and are expressed only in the trophectoderm (outer epithelium of the developing placenta) from the time of blastocyst hatching to implantation. Leukemia inhibitory factor (LIF) is a multi-functional cytokine which is expressed by uterine endometrium of pregnant mice around day 4 of pregnancy. Female mice lacking a functional LIF gene are fertile but their blastocysts fail to implant, strongly implicating the cytokine in maternal control of implantation. Colony stimulating factors (CSF) are a family of proteins (GM-CSF, CSF-1, G-CSF, and IL-3) that stimulate the cellular proliferation and induction of terminal differentiation of hemopoietic progenitor cells. CSF-1 is expressed in the uterine endometrium of the mouse and human during early pregnancy and its receptor, fms, is present on trophoblast. The osteopetrotic mouse, which represents a natural "knockout" of the CSF-1 gene, exhibits a low rate of fetal implantation and poor fetal viability. It seems likely that CSF-1 expression by the uterus influences growth and differentiation of the placenta. Although different species may utilize different strategies for ensuring developmental and endocrinological coordination between the embryo and the mother, these three examples illustrate that cytokines are likely to be major participants as autocrine factors that direct the events of early pregnancy and not simply as modulators of the maternal immune system.
细胞因子在生殖系统的多种细胞类型中表达，尽管在大多数情况下其功能尚不清楚。然而，在少数情况下，其在早期妊娠中的作用已得到证实。首先，反刍有蹄类动物（如牛、羊和山羊）的植入前胚胎会分泌一种独特的I型干扰素（IFN-τ）。通过仍不清楚的机制，IFN-τ可防止黄体溶解，从而确保孕酮的持续分泌，而孕酮对维持妊娠至关重要。很可能IFN-τ通过调节子宫中促黄体溶解激素前列腺素F2α的分泌来防止黄体溶解。尽管IFN-τ参与妊娠过程，但其具有与其他I型干扰素（如IFN-α）类似的抗增殖和抗病毒活性。绵羊和牛体内有4至5个IFN-τ基因，其启动子区域高度保守，且与其他I型干扰素的启动子区域不同。这些基因不能被病毒诱导，仅在囊胚孵化至着床期间，在滋养外胚层（发育中胎盘的外层上皮）中表达。白血病抑制因子（LIF）是一种多功能细胞因子，在妊娠第4天左右由怀孕小鼠的子宫内膜表达。缺乏功能性LIF基因的雌性小鼠具有生育能力，但其囊胚无法着床，这有力地表明该细胞因子参与了母体对着床的控制。集落刺激因子（CSF）是一类蛋白质（GM-CSF、CSF-1、G-CSF和IL-3），可刺激造血祖细胞的细胞增殖并诱导其终末分化。CSF-1在小鼠和人类妊娠早期的子宫内膜中表达，其受体fms存在于滋养层细胞上。骨质石化小鼠代表CSF-1基因的天然“敲除”模型，其胎儿着床率低且胎儿存活率差。子宫表达的CSF-1似乎会影响胎盘的生长和分化。尽管不同物种可能采用不同策略来确保胚胎与母体之间的发育和内分泌协调，但这三个例子表明，细胞因子可能是指导早期妊娠事件的主要自分泌因子参与者，而不仅仅是母体免疫系统的调节剂。
