Lobo Shalini C, Huang S-T Joseph, Germeyer Ariane, Dosiou Chrysoula, Vo Kim Chi, Tulac Suzana, Nayak Nihar R, Giudice Linda C
Department of Gynecology and Obstetrics, Stanford University Medical Center, Stanford, CA 94305-5317, USA.
Am J Reprod Immunol. 2004 Oct;52(4):244-51. doi: 10.1111/j.1600-0897.2004.00217.x.
Changes in the immune environment in the endometrium are believed to be important for successful implantation and maintenance of pregnancy. We have previously investigated global gene profiling in human endometrium during the window of implantation by oligonucleotide microarray technology, and analysis of these data underscore the regulation of a group of immune-related genes. The present study was therefore conducted to examine the pattern of expression and regulation of these genes including decay accelerating factor (DAF), indoleamine 2,3 dioxygenase (IDO), interleukin-15 (IL-15), IL-15 receptor alpha subunit (IL-15Ralpha), interferon regulatory factor-1 (IRF-1), lymphotactin (Lpn), natural killer-associated transcript 2 (NKAT2) and NKG5 in secretory and proliferative human endometrium.
Endometrial biopsies were obtained from normally cycling women in the late proliferative and mid-secretory phase of the menstrual cycle. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot analysis were used to determine the expression and regulation of these genes in secretory and proliferative human endometrium. Cellular localization of NKG5, Lpn and IDO by in situ hybridization in secretory-phase endometrium was also examined.
Semi-quantitative RT-PCR and Northern blot results demonstrate that there is a coordinated upregulation of this group of genes during the window of implantation.
We demonstrate the upregulation of immune-related genes IL-15Ralpha, Lpn and NKG5 in secretory versus proliferative human endometrium. We also demonstrate a similar upregulation in secretory endometrium of other immune-related genes, viz, DAF, IDO, IL-15, IRF-1 and NKAT2. The functions of these genes include stimulation of proliferation of uterine natural killer (uNK) cells, inhibition of cytolytic activity of uNK cells, inhibition of cell growth of T cells and other pathogens and inhibition of the classical complement pathway. Upregulation of these immune-related genes in the window of implantation suggests their role during the process of implantation and in immune tolerance of the implanting conceptus.
子宫内膜免疫环境的变化被认为对成功着床和维持妊娠至关重要。我们之前通过寡核苷酸微阵列技术研究了植入窗期人类子宫内膜的全基因组图谱，对这些数据的分析强调了一组免疫相关基因的调控。因此，本研究旨在检测这些基因，包括衰变加速因子（DAF）、吲哚胺2,3-双加氧酶（IDO）、白细胞介素-15（IL-15）、IL-15受体α亚基（IL-15Rα）、干扰素调节因子-1（IRF-1）、淋巴细胞趋化因子（Lpn）、自然杀伤细胞相关转录本2（NKAT2）和NKG5在分泌期和增殖期人类子宫内膜中的表达模式及调控情况。
从月经周期处于增殖晚期和分泌中期的正常月经周期女性获取子宫内膜活检组织。采用半定量逆转录聚合酶链反应（RT-PCR）和Northern印迹分析来确定这些基因在分泌期和增殖期人类子宫内膜中的表达及调控情况。还通过原位杂交检测了分泌期子宫内膜中NKG5、Lpn和IDO的细胞定位。
半定量RT-PCR和Northern印迹结果表明，在植入窗期这组基因存在协同上调。
我们证明了免疫相关基因IL-15Rα、Lpn和NKG5在分泌期与增殖期人类子宫内膜中上调。我们还证明了其他免疫相关基因，即DAF、IDO、IL-15、IRF-1和NKAT2在分泌期子宫内膜中也有类似上调。这些基因的功能包括刺激子宫自然杀伤（uNK）细胞增殖、抑制uNK细胞的细胞溶解活性、抑制T细胞和其他病原体的细胞生长以及抑制经典补体途径。这些免疫相关基因在植入窗期上调表明它们在着床过程以及对植入胚胎的免疫耐受中发挥作用。
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