Abstract
Tumor necrosis factor receptor subfamily 9 (TNFRSF9) plays a potentially important general role in immune function. Tnfrsf9 gene expression has previously been characterized in late pregnant mouse uterus and placenta. However, little is known about its expression in the uterus during the implantation phase of early pregnancy. We have assessed the levels and localization of Tnfrsf9 expression in the mouse uterus and conceptus during implantation. Relative Tnfrsf9 mRNA levels were significantly higher in implantation than in non-implantation site tissue on days 6.5-8.5 of pregnancy. This increase did not depend on the presence of the conceptus, as mRNA levels were not significantly different between pregnant implantation sites and artificially induced deciduomas. Localization by in situ hybridization revealed a subpopulation of endothelial and uterine natural killer cells expressing Tnfrsf9 in the endometrium during implantation. In the developing conceptus, primary trophoblast giant and ectoplacental cells expressed Tnfrsf9 on days 6.5-8.5, followed by expression in the trophoblast giant cell layers surrounding the conceptus on day 9.5 of pregnancy. Two main splice forms of Tnfrsf9 mRNA exist and encode proteins with distinct biological functions; both mRNA splice forms were present in uterine and conceptus tissues as determined by reverse transcription with the polymerase chain reaction. Thus, both membrane and soluble forms of Tnfrsf9 are expressed in specific cell types of the uterus and conceptus during the progression of implantation in mice and possibly have an important function in this process.
Highlights
Mammalian implantation is the process by which the conceptus comes into intimate contact with the maternal blood supply
Relative tumor necrosis factor receptor superfamily member 9 (Tnfrsf9) mRNA levels were determined in uteri of pregnant mice on Days 3.5-8.5 of pregnancy using quantitative RT-PCR (qRT-PCR) (Figure 1a)
The Tnfrsf9 gene is believed to play key roles in several aspects of immunity (Croft, 2003, Gellersen, Brosens and Brosens, 2007, Heinisch, Bizer, Volgger and Simon, 2001, Heinisch, Daigle, Knopfli and Simon, 2000, Kim, Chang, Lee, Lee, Kim, Kwon and Kang, 2008, Marvel and Walzer, 2010, Michel and Schwarz, 2000, Myers and Vella, 2005, Nishimoto, Lee, Hong, Potter, Maeda-Yamamoto, Kinoshita, Kawakami, Mittler, Kwon, Ware, Croft and Kawakami, 2005, Pollok, Kim, Zhou, Hurtado, Kim, Pickard and Kwon, 1993, Salih, et al, 2002, Vinay, Cha and Kwon, 2006, Zhang, Voskens, Sallin, Maniar, Montes, Zhang, Lin, Li, Burch, Tan, Hertzano, Chapoval, Tamada, Gastman, Schulze and Strome, 2010) but little is known about its role, if any, in the immunology of early pregnancy
Summary
Mammalian implantation is the process by which the conceptus comes into intimate contact with the maternal blood supply This process is necessary for the mother to adequately provide nutrients for fetal development and successful completion of pregnancy. One of the first maternal changes during implantation in rodents and humans is a dramatic transformation of the endometrial tissue into decidual tissue (Abrahamsohn and Zorn, 1993, Gellersen, et al, 2007, Mori, et al, 1991). The hallmark of this change is the differentiation of endometrial fibroblasts into decidual cells, commonly referred to as decidualization or decidual cell differentiation. After the onset of implantation the trophectoderm cells give rise to trophoblast giant cells, ectoplacental cone cells and spongiotrophoblast cells all of which contribute to the developing placenta (Cross, 2000)
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