V-ATPase upregulation during early pregnancy: a possible link to establishment of an inflammatory response during preimplantation period of pregnancy
V-ATPase upregulation during early pregnancy: a possible link to establishment of an inflammatory response during preimplantation period of pregnancy
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DOI：
10.1530/rep-12-0036
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发表时间：
2012-05-01
期刊：
影响因子：
3.8
通讯作者：
Beaman, Kenneth D.
中科院分区：
文献类型：
--
作者：
Jaiswal, Mukesh K.;Mallers, Timothy M.;Beaman, Kenneth D.
存在各种机制来防止潜在的有害母体免疫反应，从而导致半异基因胎儿的存活受到损害。在妊娠期，有必要的植入前炎症阶段，随后是植入后抗炎阶段。因此，在怀孕期间观察到了一种双相‘免疫反应’。我们提供了精子获能诱导精子中a2亚型的V-ATPase(ATP6V0A2，简称a2V)、白血病抑制因子(LIF)、IL1b和肿瘤坏死因子的表达的证据。获能精子还释放切割的2V-ATPase N-末端结构域(A2NTD)，上调子宫中Lif、IL1b、肿瘤坏死因子和单核细胞趋化蛋白-1(CCL2(Mcp1))的基因表达。未受精卵中a2V的表达较低，受精后受精卵中a2V的表达增加。在植入前的胚胎中，这种增加的a2V表达水平保持不变。在植入前胚胎中，精浆是上调a2V表达所必需的，因为与精囊缺陷的雄性交配不能诱导植入前胚胎中a2V表达的增加。在妊娠着床前，精子和精浆人工授精后，巨噬细胞在子宫内的渗入明显增加。这种向子宫的动态渗透通过诱导CCL2的表达与子宫a2V的表达相对应。此外，用精子和精浆同时授精的雌性小鼠子宫中M1：M2(促炎/抗炎)巨噬细胞的极化比在1.60(第1天)到1.45(第4天)之间波动。这些数据提供的证据表明，暴露在精液中可能通过诱导a2V和细胞因子/趋化因子的表达来启动炎症环境，从而触发巨噬细胞在怀孕开始时涌入植入前子宫，最终导致成功妊娠结局。繁衍(2012)143 713-725
Various mechanisms exist to prevent a potentially deleterious maternal immune response that results in compromising survival of semiallogeneic fetus. In pregnancy, there is a necessary early preimplantation inflammatory stage followed by a postimplantation anti-inflammatory stage. Thus, there is a biphasic 'immune response' observed during the course of pregnancy. We provide the evidence that capacitation of sperm induced the expression of a2 isoform of V-ATPase (ATP6V0A2 referred to as a2V), leukemia inhibitory factor (Lif), Il1b, and Tnf in the sperm. Capacitated sperm also released cleaved N-terminal domain of a2V-ATPase (a2NTD), which upregulates the gene expression of Lif, Il1b, Tnf, and monocyte chemotactic protein-1 (Ccl2 (Mcp1)) in the uterus. Unfertilized eggs had low a2V expression, but after fertilization, the expression of a2V increased in zygotes. This increased level of a2V expression was maintained in preimplantation embryos. Seminal plasma was necessary for upregulation of a2V expression in preimplantation embryos, as mating with seminal vesicle-deficient males failed to elicit an increase in a2V expression in preimplantation embryos. The infiltration of macrophages into the uterus was significantly increased after insemination of both sperm and seminal plasma during the preimplantation period of pregnancy. This dynamic infiltration into the uterus corresponded with the uterine a2V expression through the induction of Ccl2 expression. Furthermore, the polarization ratio of M1:M2 (pro-inflammatory/anti- inflammatory) macrophages in the uterus fluctuated from a ratio of 1.60 (day 1) to 1.45 (day 4) when female mice were inseminated with both sperm and seminal plasma. These data provide evidence that exposure to semen may initiate an inflammatory milieu by inducing a2V and cytokine/chemokine expression, which triggers the influx of macrophages into the preimplantation uterus during the onset of pregnancy and ultimately leads to successful pregnancy outcome. Reproduction (2012) 143 713-725