Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA.
Reproduction. 2012 May;143(5):713-25. doi: 10.1530/REP-12-0036. Epub 2012 Mar 27.
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.
存在多种机制来防止潜在的有害的母体免疫反应，这种反应会危及半同种异体胎儿的存活。在妊娠期间，存在一个必要的早期着床前炎症阶段，随后是着床后抗炎阶段。因此，在妊娠过程中观察到一个双相的“免疫反应”。我们提供的证据表明，精子的获能诱导了 V-ATPase 的 a2 同工型（ATP6V0A2 称为 a2V）、白血病抑制因子（Lif）、Il1b 和 Tnf 在精子中的表达。获能的精子还释放了 a2V-ATPase 的裂解 N 端结构域（a2NTD），这上调了 Lif、Il1b、Tnf 和单核细胞趋化蛋白-1（Ccl2（Mcp1））在子宫中的基因表达。未受精的卵子 a2V 表达水平较低，但受精后，合子中 a2V 的表达增加。这种 a2V 表达水平的增加在着床前胚胎中得到维持。精子精液是上调着床前胚胎中 a2V 表达所必需的，因为与缺乏精囊的雄性交配未能在着床前胚胎中引起 a2V 表达的增加。在妊娠的着床前期间，精子和精液的授精后，巨噬细胞渗透到子宫中的数量显著增加。这种动态的渗透与通过诱导 Ccl2 表达的子宫 a2V 表达相对应。此外，当雌性小鼠接受精子和精液授精时，子宫中 M1:M2（促炎/抗炎）巨噬细胞的极化比例从 1.60（第 1 天）波动到 1.45（第 4 天）。这些数据提供的证据表明，暴露于精液可能通过诱导 a2V 和细胞因子/趋化因子的表达来引发炎症环境，这触发了巨噬细胞在妊娠开始时涌入着床前子宫，并最终导致成功的妊娠结局。
