Select Nutrients in the Ovine Uterine Lumen. V. Nitric Oxide Synthase, GTP Cyclohydrolase, and Ornithine Decarboxylase in Ovine Uteri and Peri-Implantation Conceptuses
Select Nutrients in the Ovine Uterine Lumen. V. Nitric Oxide Synthase, GTP Cyclohydrolase, and Ornithine Decarboxylase in Ovine Uteri and Peri-Implantation Conceptuses
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DOI：
10.1095/biolreprod.108.075473
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发表时间：
2009-07-01
影响因子：
3.6
通讯作者：
Bazer, Fuller W.
中科院分区：
文献类型：
--
作者：
Gao, Haijun;Wu, Guoyao;Bazer, Fuller W.
一氧化氮（NO）和多胺对于孕体（胚胎和胚外膜）的植入和发育至关重要，但调节其在子宫和孕体中的生物合成的机制在很大程度上是未知的。本研究确定了动情周期、妊娠、孕激素和干扰素tau（IFNT）对一氧化氮合酶表达的影响。（NOS 1、NOS 2和NOS 3）、鸟苷三磷酸（GTP）环化水解酶（GCH 1，从头合成四氢生物蝶呤的关键酶，一种NO产生的辅因子），和鸟氨酸脱羧酶（ODC 1）在月经期母羊（第10-16天）和妊娠母羊（第10-20天）的子宫内膜中。NOS 1和ODC 1的mRNA和蛋白质在子宫腔上皮（LE）和浅表腺上皮（sGE）中含量最高，且含量受发情周期和早孕天数的影响。NOS 2，GCH 1，和NOS 3的mRNA检测到非常低的丰度在子宫上皮细胞和基质细胞在周期和怀孕母羊。NOS 1 mRNA在孕体中也表达很弱，而NOS 3 mRNA在孕体的滋养外胚层和内胚层中丰富，总NOS 1和NOS 3蛋白、抑制性p-NOS 1蛋白和刺激性p-NOS 3蛋白也是如此。GCH 1 mRNA在妊娠第13和15天的滋养外胚层和内胚层中丰富，然后下降，而ODC 1 mRNA丰度在妊娠第13和18天之间增加。GCH 1蛋白主要定位于滋养外胚层和内胚层的细胞核中，其丰度在妊娠第14天后下降，而ODC 1蛋白在妊娠第13天和第18天之间的滋养外胚层中比内胚层中更丰富。孕酮刺激LE/sGE和腺上皮中NOS 1和GCH 1的表达，而IFNT抑制这些细胞类型中的NOS 1的表达。因此，绵羊子宫内膜和孕体中NO和多胺的生物合成可能在转录、翻译和翻译后水平上受到调节，以有利于孕体发育和着床。
Nitric oxide (NO) and polyamines are critical for implantation and development of conceptuses (embryo and extraembryonic membranes), but mechanisms regulating their biosynthesis in uteri and conceptuses are largely unknown. This study determined the effects of the estrous cycle, pregnancy, progesterone, and interferon tau (IFNT) on expression of NO synthases (NOS1, NOS2, and NOS3), guanosine triphosphate (GTP) cyclohydrolase (GCH1, the key enzyme in de novo synthesis of tetrahydrobiopterin, a cofactor for NO production), and ornithine decarboxylase (ODC1) in uterine endometria in cyclic ewes (Days 10-16) and pregnant ewes (Days 10-20). The mRNAs and proteins for NOS1 and ODC1 were most abundant in uterine luminal (LE) and superficial glandular (sGE) epithelia, and abundance was affected by day of estrous cycle and early pregnancy. NOS2, GCH1, and NOS3 mRNAs were detected in very low abundance in uterine epithelia and stromal cells in both cyclic and pregnant ewes. NOS1 mRNA also was expressed very weakly in conceptuses, whereas NOS3 mRNA was abundant in the trophectoderm and endoderm of conceptuses, as were total NOS1 and NOS3 proteins, inhibitory p-NOS1 protein, and stimulatory p-NOS3 protein. GCH1 mRNA was abundant in the trophectoderm and endoderm of conceptuses between Days 13 and 15 of pregnancy and then decreased thereafter, whereas ODC1 mRNA abundance increased in conceptuses between Days 13 and 18 of pregnancy. GCH1 protein was localized primarily in the nuclei of trophectoderm and endoderm, and its abundance decreased after Day 14 of pregnancy, whereas ODC1 protein was more abundant in the trophectoderm than in the endoderm between Days 13 and 18 of pregnancy. Progesterone stimulated NOS1 and GCH1 expression in LE/sGE and glandular epithelia, whereas IFNT inhibited NOS1 expression in these cell types. Thus, biosynthesis of NO and polyamines in ovine uterine endometria and conceptuses is potentially regulated at transcriptional, translational, and posttranslational levels to favor conceptus development and implantation.