Abstract
N-acetylneuraminate pyruvate lyase (NPL) catalyzes N-acetylneuraminic acid, the predominant sialic acid. Microarray analysis of the periimplantation mouse uterine luminal epithelium (LE) revealed Npl being the most downregulated (35×) gene in the LE upon embryo implantation. In natural pregnant mouse uterus, Npl expression increased 56× from gestation day 0.5 (D0.5) to D2.5. In ovariectomized mouse uterus, Npl was significantly upregulated by progesterone (P4) but downregulated by 17β-estradiol (E2). Progesterone receptor (PR) antagonist RU486 blocked the upregulation of Npl in both preimplantation uterus and P4-treated ovariectomized uterus. Npl was specifically localized in the preimplantation D2.5 and D3.5 uterine LE. Since LE is essential for establishing uterine receptivity, it was hypothesized that NPL might play a critical role in uterine function, especially during embryo implantation. This hypothesis was tested in the Npl (−/−) mice. No significant differences were observed in the numbers of implantation sites on D4.5, gestation periods, litter sizes, and postnatal offspring growth between wild type (WT) and Npl (−/−) females from mating with WT males. Npl (−/−)xNpl (−/−) crosses produced comparable little sizes as that from WTxWT crosses. Comparable mRNA expression levels of several genes involved in sialic acid metabolism were observed in D3.5 uterus and uterine LE between WT and Npl (−/−), indicating no compensatory upregulation in the D3.5 Npl (−/−) uterus and LE. This study demonstrates PR-mediated dynamic expression of Npl in the periimplantation uterus and dispensable role of Npl in uterine function and embryo development.
Highlights
N-acetylneuraminate pyruvate lyase (NPL), named sialic acid aldolase or N-acetylneuraminate lyase, was originally purified and characterized in human related pathogenic as well as nonpathogenic bacteria that utilize the carbon sources in the mucusrich surfaces of the human body, such as Clostridium perfringens and Escherichia coli [1,2,3,4]
Realtime PCR indicated that Npl was expressed at a very low level in the D0.5 uterus; it was increased 46 in the D1.5 uterus and 566 in the D2.5 uterus; its expression level was slightly lower (446) in the D3.5 uterus compared to that in the D2.5 uterus; upon embryo implantation, Npl expression level in the D4.5 uterus returned to a level comparable to that of D1.5 uterus (Fig. 1A)
Npl was exclusively detected in the uterine luminal epithelium (LE) on D2.5 and D3.5 with comparable intensity (Figs. 1D, 1E) but undetectable in the postimplantation uterus from D4.5 to D7.5 (Fig. 1F and data not shown)
Summary
N-acetylneuraminate pyruvate lyase (NPL), named sialic acid aldolase or N-acetylneuraminate lyase, was originally purified and characterized in human related pathogenic as well as nonpathogenic bacteria that utilize the carbon sources in the mucusrich surfaces of the human body, such as Clostridium perfringens and Escherichia coli [1,2,3,4]. NPL catalyzes the breaking of carbon-carbon bonds of Nacetylneuraminic acid, the predominant sialic acid, into Nacetylmannosamine and pyruvate, regulating the cellular concentrations of sialic acid and preventing the recycling of sialic acid for further sialiation with glycoconjuates in the Golgi compartment [8,9]. In both bacteria and mammalians, sialic acids such as N-acetylneuraminic acid (Neu5Ac) and N-glycolylneur aminic acid (Neu5Gc) are involved in the sialylation and provide the diversity of sialylated oligosaccharides [10,11,12].
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