Alkaline phosphatases contribute to uterine receptivity, implantation, decidualization, and defense against bacterial endotoxin in hamsters.
Alkaline phosphatases contribute to uterine receptivity, implantation, decidualization, and defense against bacterial endotoxin in hamsters.
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DOI：
10.1530/rep-13-0153
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Paria BC
中科院分区：
文献类型：
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作者：
Lei W;Nguyen H;Brown N;Ni H;Kiffer-Moreira T;Reese J;Millán JL;Paria BC
碱性磷酸酶（AP）活性已在几个物种的子宫中得到证实，但其在子宫中的重要性，在一般情况下和怀孕期间，尚未被揭示。在这项研究中，我们专注于确定AP同工酶类型，和它们的激素调节，细胞类型和事件特异性表达和可能的功能在仓鼠子宫在周期和早期妊娠。我们的RT-PCR和原位杂交研究表明，在已知的Akp 2，Akp 3，Akp 5和Akp 6小鼠AP同工酶基因，仓鼠子宫表达只有Akp 2和Akp 6，和这两个基因共同表达在管腔上皮细胞。在周期性和卵巢切除仓鼠中的研究确定，虽然孕酮是主要的子宫Akp 2诱导剂，但孕酮和雌激素都是强Akp 6调节剂。在植入前子宫的研究表明，在子宫容受性的腔上皮细胞的基因和其编码的同工酶的活性的诱导。然而，在植入开始时，Akp 2在植入胚胎周围的腔上皮细胞中的表达减少。与此相反，Akp 6及其同工酶的表达维持在腔上皮细胞邻近，但不远离，植入的胚胎。植入后，间质转化为蜕膜与诱导表达的Akp 2及其同工酶。我们接下来证明了子宫AP在其产生和活性位点对内毒素脂多糖进行去磷酸化和解毒。两者合计，我们的研究结果表明，子宫AP有助于子宫容受性，植入和蜕膜化，除了它们的作用，保护子宫和妊娠免受细菌感染。
Alkaline phosphatase (AP) activity has been demonstrated in the uterus of several species, but its importance in the uterus, in general and during pregnancy, is yet to be revealed. In this study, we focused on identifying AP isozyme types, and their hormonal regulation, cell-type and event-specific expression and possible functions in the hamster uterus during the cycle and early pregnancy. Our RT-PCR and in situ hybridization studies demonstrated that among the known Akp2, Akp3, Akp5 and Akp6 murine AP isozyme genes, hamster uteri express only Akp2 and Akp6; and both genes are co-expressed in luminal epithelial cells. Studies in cyclic and ovariectomized hamsters established that while progesterone is the major uterine Akp2 inducer, both progesterone and estrogen are strong Akp6 regulators. Studies in preimplantation uteri showed induction of both genes and the activity of their encoded isozymes in luminal epithelial cells during uterine receptivity. However, at the beginning of implantation, Akp2 showed reduced expression in luminal epithelial cells surrounding the implanted embryo. In contrast, expression of Akp6 and its isozyme was maintained in luminal epithelial cells adjacent to, but not away from, the implanted embryo. Following implantation, stromal transformation to decidua was associated with induced expressions of only Akp2 and its isozyme. We next demonstrated that uterine APs dephosphorylate and detoxify endotoxin lipopolysaccharide at their sites of production and activity. Taken together, our findings suggest that uterine APs contribute to uterine receptivity, implantation, and decidualization in addition to their role in protection of the uterus and pregnancy against bacterial infection.