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Comparative Study
. 2007 Jun;133(6):1213-21.
doi: 10.1530/REP-07-0085.

The conceptus increases secreted phosphoprotein 1 gene expression in the mouse uterus during the progression of decidualization mainly due to its effects on uterine natural killer cells

Jennifer L Herington  1 , Brent M Bany
Affiliations
Comparative Study

The conceptus increases secreted phosphoprotein 1 gene expression in the mouse uterus during the progression of decidualization mainly due to its effects on uterine natural killer cells

Jennifer L Herington et al. Reproduction. 2007 Jun.

Abstract

Within the mouse endometrium, secreted phosphoprotein 1 (SPP1) gene expression is mainly expressed in the luminal epithelium and some macrophages around the onset of implantation. However, during the progression of decidualization, it is expressed mainly in the mesometrial decidua. To date, the precise cell types responsible for the expression in the mesometrial decidua has not been absolutely identified. The goal of the present study was to assess the expression of SPP1 in uteri of pregnant mice (decidua) during the progression of decidualization and compared it with those undergoing artificially induced decidualization (deciduoma). Significantly (P<0.05) greater steady-state levels of SPP1 mRNA were seen in the decidua when compared with deciduoma. Further, in the decidua, the majority of the SPP1 protein was localized within a subpopulation of granulated uterine natural killer (uNK) cells but not co-localized to their granules. However, in addition to being localized to uNK cells, SPP1 protein was also detected in another cell type(s) that were not epidermal growth factor-like containing mucin-like hormone receptor-like sequence 1 protein-positive immune cells that are known to be present in the uterus at this time. Finally, decidual SPP1 expression dramatically decreased in uteri of interleukin-15-deficient mice that lack uNK cells. In conclusion, SPP1 expression is greater in the mouse decidua when compared with the deciduoma after the onset of implantation during the progression of decidualization. Finally, uNK cells were found to be the major source of SPP1 in the pregnant uterus during decidualization. SPP1 might play a key role in uNK killer cell functions in the uterus during decidualization.

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Figures

Figure 1
Figure 1
Time-line showing the preparation and collection of mouse uteri during decidualization. Decidual tissue samples were collected on Days 6.5, 7.5 and 8.5 of pregnancy, corresponding to Days 2, 3 and 4 after the onset of decidualization, respectively (A). Deciduomal tissue samples from ovariectomized mice treated with estradiol-17β (E2) and/or progesterone (P4) were collected on Days 2, 3 and 4 after the onset of decidualization in response to an intra-luminal injection of sesame oil (B).
Figure 2
Figure 2
RT-real-time-PCR analysis showing relative steady-state Spp1 mRNA levels in the mouse decidua and deciduoma on Days 2, 3 and 4 after the onset of decidualization. Bars represent the mean (±SEM; N= 4) and those with different letters on a given day are significantly different (P <0.05).
Figure 3
Figure 3
Double fluorescent co-localization of SPP1 and DBA lectin binding in cross-sections of the mouse uterus during the progression of decidualization. Representative photomicrographs of the deciduoma (A, B, E, F, I and J) and decidua (C, D, G, H, K and L) on Days 2 (upper row), 3 (middle row) and 4 (lower row) after the onset of decidualization. Green, red and blue fluorescence localizes DBA lectin-positive uNK cells, SPP1 localization and nuclei, respectively. Scale bars = 0.5 mm. For all photomicrographs, sections are oriented with the antimesometrial (AM) side up and mesometrial (M) side down.
Figure 4
Figure 4
Cell types in the mesometrial region of the mouse decidua and deciduoma that contain SPP1 during the progression of decidualization. DBA lectin-positive uNK cell types (I–IV) that do not (A) and do contain (B) SPP1 were seen. Some SPP1 was localized to DBA lectin-negative cells (C) but these cells were not EMR1 positive (D). Green, red and blue fluorescence shows DBA lectin-positive uNK cells or EMR1, SPP1 and nuclei, respectively. Graph representing the mean percentage of uNK cell types (I–IV) that do not (SPP1−) or do (SPP1+) stain positive for SPP1 in the total mesometrial region of the deciduomas and deciduas on Days 2 (upper graph), 3 (middle graph) and 4 (lower graph) after the onset of decidualization (E). Bars represent the mean (±SEM; N= 4–7) and ND denotes none detected.
Figure 5
Figure 5
Graphs showing the percentage of cells in the deciduoma and decidua staining positive for DBA lectin binding (DBA+) and/or SPP1 (SPP1+/SPP1−) in the mesometrial region of the mouse uterus during the progression of decidualization on Days 2 (upper graph), 3 (middle graph) and 4 (lower graph) after the onset of decidualization. Bars represent the mean (±SEM; N= 4–7) and those with different letters are significantly different (P <0.05).
Figure 6
Figure 6
SPP1 expression in the decidua on Day 3 after the onset of decidualization in Il15+/+ compared to Il15−/− mice. Bar graph summarizing the RT-real time-PCR analysis showing relative steady-state levels of Spp1 mRNA in the decidua of Il15+/+ compared to Il15−/− mice on Day 3 after the onset of decidualization (A). Representative photomicrographs of DBA lectin- and SPP1-stained cross-sections of the mouse decidua from Il15+/+ (B) and Il15−/− mice (C). Green and red fluorescent colors indicate DBA lectin binding and SPP1 localization, respectively. Bars represent the mean (±SEM; N= 4) and those with different letters are significantly different (P <0.01). For both photomicrographs, sections are oriented with the mesometrial (M) side down and also shown is the conceptus (C).
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References

    1. Apparao KB, Murray MJ, Fritz MA, Meyer WR, Chambers AF, Truong PR, Lessey BA. Osteopontin and its receptor alphavbeta(3) integrin are coexpressed in the human endometrium during the menstrual cycle but regulated differentially. J Clin Endocrinol Metab. 2001;86:4991–5000. - PubMed
    1. Ashkar AA, Black GP, Wei Q, He H, Liang L, Head JR, Croy BA. Assessment of requirements for IL-15 and IFN regulatory factors in uterine NK cell differentiation and function during pregnancy. J Immunol. 2003;171:2937–2944. - PubMed
    1. Austyn JM, Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981;11:805–815. - PubMed
    1. Bany BM, Cross JC. Post-implantation mouse conceptuses produce paracrine signals that regulate the uterine endometrium undergoing decidualization. Dev Biol. 2006;294:445–456. - PubMed
    1. Barber EM, Pollard JW. The uterine NK cell population requires IL-15 but these cells are not required for pregnancy nor the resolution of a Listeria monocytogenes infection. J Immunol. 2003;171:37–46. - PubMed

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