Skip to main content

Advertisement

SpringerLink
Log in

Adam12 plays a role during uterine decidualization in mice

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

In mouse, decidualization is characterized by the proliferation of stromal cells and their differentiation into specialized type of cells (decidual cells) with polyploidy, surrounding the implanting blastocyst. However, the mechanisms involved in these processes remain poorly understood. Using multiple approaches, we have examined the role of Adam12 in decidualization during early pregnancy in mice. Adam12 is spatiotemporally expressed in decidualizing stromal cells in intact pregnant females and in pseudopregnant mice undergoing artificially induced decidualization. In the ovariectomized mouse uterus, the expression of Adam12 is upregulated after progesterone treatment, which is primarily mediated by nuclear progesterone receptor. In a stromal cell culture model, the expression of Adam12 gradually rises with the progression of stromal decidualization, whereas the attenuated expression of Adam12 after siRNA knockdown significantly blocks the progression of decidualization. Our study suggests that Adam12 is involved in promoting uterine decidualization during pregnancy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Atfi A, Dumont E, Colland F, Bonnier D, L'Helgoualc'h A, Prunier C, Ferrand N, Clement B, Wewer UM, Theret N (2007) The disintegrin and metalloproteinase ADAM12 contributes to TGF-beta signaling through interaction with the type II receptor. J Cell Biol 178:201–208

    Article  CAS  PubMed  Google Scholar 

  • Carl-McGrath S, Lendeckel U, Ebert M, Roessner A, Rocken C (2005) The disintegrin-metalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer. Int J Oncol 26:17–24

    CAS  PubMed  Google Scholar 

  • Das SK (2009) Cell cycle regulatory control for uterine stromal cell decidualization in implantation. Reproduction 137:889–899

    Article  CAS  PubMed  Google Scholar 

  • Das SK, Lim H, Paria BC, Dey SK (1999) Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy. J Mol Endocrinol 22:91–101

    Article  CAS  PubMed  Google Scholar 

  • Dey SK, Lim H, Das SK, Reese J, Paria BC, Daikoku T, Wang H (2004) Molecular cues to implantation. Endocr Rev 25:341–373

    Article  CAS  PubMed  Google Scholar 

  • Frohlich C, Albrechtsen R, Dyrskjot L, Rudkjaer L, Orntoft TF, Wewer UM (2006) Molecular profiling of ADAM12 in human bladder cancer. Clin Cancer Res 12:7359–7368

    Article  PubMed  Google Scholar 

  • Garcia R, Bowman TL, Niu G, Yu H, Minton S, Muro-Cacho CA, Cox CE, Falcone R, Fairclough R, Parsons S, Laudano A, Gazit A, Levitzki A, Kraker A, Jove R (2001) Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 20:2499–2513

    Article  CAS  PubMed  Google Scholar 

  • Grana X, Reddy EP (1995) Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 11:211–219

    CAS  PubMed  Google Scholar 

  • Herzinger T, Reed SI (1998) Cyclin D3 is rate-limiting for the G1/S phase transition in fibroblasts. J Biol Chem 273:14958–14961

    Article  CAS  PubMed  Google Scholar 

  • Hess AP, Hamilton AE, Talbi S, Dosiou C, Nyegaard M, Nayak N, Genbecev-Krtolica O, Mavrogianis P, Ferrer K, Kruessel J, Fazleabas AT, Fisher SJ, Giudice LC (2007) Decidual stromal cell response to paracrine signals from the trophoblast: amplification of immune and angiogenic modulators. Biol Reprod 76:102–117

    Article  CAS  PubMed  Google Scholar 

  • Iba K, Albrechtsen R, Gilpin BJ, Loechel F, Wewer UM (1999) Cysteine-rich domain of human ADAM 12 (meltrin alpha) supports tumor cell adhesion. Am J Pathol 154:1489–1501

    CAS  PubMed  Google Scholar 

  • Ito N, Nomura S, Iwase A, Ito T, Kikkawa F, Tsujimoto M, Ishiura S, Mizutani S (2004) ADAMs, a disintegrin and metalloproteinases, mediate shedding of oxytocinase. Biochem Biophys Res Commun 314:1008–1013

    Article  CAS  PubMed  Google Scholar 

  • Kawaguchi N, Sundberg C, Kveiborg M, Moghadaszadeh B, Asmar M, Dietrich N, Thodeti CK, Nielsen FC, Moller P, Mercurio AM, Albrechtsen R, Wewer UM (2003) ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function. J Cell Sci 116:3893–3904

    Article  CAS  PubMed  Google Scholar 

  • Kveiborg M, Frohlich C, Albrechtsen R, Tischler V, Dietrich N, Holck P, Kronqvist P, Rank F, Mercurio AM, Wewer UM (2005) A role for ADAM12 in breast tumor progression and stromal cell apoptosis. Cancer Res 65:4754–4761

    Article  CAS  PubMed  Google Scholar 

  • Le Pabic H, Bonnier D, Wewer UM, Coutand A, Musso O, Baffet G, Clement B, Theret N (2003) ADAM12 in human liver cancers: TGF-beta-regulated expression in stellate cells is associated with matrix remodeling. Hepatology 37:1056–1066

    Article  PubMed  Google Scholar 

  • Leeman RJ, Lui VW, Grandis JR (2006) STAT3 as a therapeutic target in head and neck cancer. Expert Opin Biol Ther 6:231–241

    Article  CAS  PubMed  Google Scholar 

  • Lendeckel U, Kohl J, Arndt M, Carl-McGrath S, Donat H, Rocken C (2005) Increased expression of ADAM family members in human breast cancer and breast cancer cell lines. J Cancer Res Clin Oncol 131:41–48

    Article  CAS  PubMed  Google Scholar 

  • Lim H, Song H, Paria BC, Reese J, Das SK, Dey SK (2002) Molecules in blastocyst implantation: uterine and embryonic perspectives. Vitam Horm 64:43–76

    Article  Google Scholar 

  • Loechel F, Fox JW, Murphy G, Albrechtsen R, Wewer UM (2000) ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3. Biochem Biophys Res Commun 278:511–515

    Article  CAS  PubMed  Google Scholar 

  • Orwig KE, Ishimura R, Muller H, Liu B, Soares MJ (1997) Identification and characterization of a mouse homolog for decidual/trophoblast prolactin-related protein. Endocrinology 138:5511–5517

    Article  CAS  PubMed  Google Scholar 

  • Pafilis J, Batistatou A, Iliopoulou A, Tsanou E, Bakogiannis A, Dassopoulos G, Charalabopoulos K (2007) Expression of adhesion molecules during normal pregnancy. Cell Tissue Res 329:1–11

    Article  CAS  PubMed  Google Scholar 

  • Seals DF, Courtneidge SA (2003) The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev 17:7–30

    Article  CAS  PubMed  Google Scholar 

  • Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ (2000) ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3. J Biol Chem 275:18574–18580

    Article  CAS  PubMed  Google Scholar 

  • Shimizu A, Maruyama T, Tamaki K, Uchida H, Asada H, Yoshimura Y (2005) Impairment of decidualization in SRC-deficient mice. Biol Reprod 73:1219–1227

    Article  CAS  PubMed  Google Scholar 

  • Spandidos A, Wang X, Wang H, Dragnev S, Thurber T, Seed B (2008) A comprehensive collection of experimentally validated primers for polymerase chain reaction quantitation of murine transcript abundance. BMC Genomics 9:633

    Article  PubMed  Google Scholar 

  • Suzuki A, Kadota N, Hara T, Nakagami Y, Izumi T, Takenawa T, Sabe H, Endo T (2000) Meltrin alpha cytoplasmic domain interacts with SH3 domains of Src and Grb2 and is phosphorylated by v-Src. Oncogene 19:5842–5850

    Article  CAS  PubMed  Google Scholar 

  • Tan J, Raja S, Davis MK, Tawfik O, Dey SK, Das SK (2002) Evidence for coordinated interaction of cyclin D3 with p21 and cdk6 in directing the development of uterine stromal cell decidualization and polyploidy during implantation. Mech Dev 111:99–113

    Article  CAS  PubMed  Google Scholar 

  • Tan Y, Li M, Cox S, Davis MK, Tawfik O, Paria BC, Das SK (2004) HB-EGF directs stromal cell polyploidy and decidualization via cyclin D3 during implantation. Dev Biol 265:181–195

    Article  CAS  PubMed  Google Scholar 

  • Tranguch S, Daikoku T, Guo Y, Wang H, Dey SK (2005) Molecular complexity in establishing uterine receptivity and implantation. Cell Mol Life Sci 62:1964–1973

    Article  CAS  PubMed  Google Scholar 

  • Vallejo G, Ballare C, Baranao JL, Beato M, Saragueta P (2005) Progestin activation of nongenomic pathways via cross talk of progesterone receptor with estrogen receptor beta induces proliferation of endometrial stromal cells. Mol Endocrinol 19:3023–3037

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Matsumoto H, Zhao X, Das SK, Paria BC (2004) Embryonic signals direct the formation of tight junctional permeability barrier in the decidualizing stroma during embryo implantation. J Cell Sci 117:53–62

    Article  CAS  PubMed  Google Scholar 

  • Yagami-Hiromasa T, Sato T, Kurisaki T, Kamijo K, Nabeshima Y, Fujisawa-Sehara A (1995) A metalloprotease-disintegrin participating in myoblast fusion. Nature 377:652–656

    Article  CAS  PubMed  Google Scholar 

  • Zahnow CA (2006) ErbB receptors and their ligands in the breast. Expert Rev Mol Med 8:1–21

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

We thank Dr. Haibin Wang (Institute of Zoology, Chinese Academy of Sciences, China) and Dr. Aaron J. W. Hsueh (Stanford University School of Medicine, USA) for helpful discussions.

Author information

Authors and Affiliations

  1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing, 100101, People’s Republic of China

    Li Zhang, Weixiang Guo, Qi Chen, Xiujun Fan, Ying Zhang & Enkui Duan

  2. Graduate University of the Chinese Academy of Sciences, 19 Yu-quan Road, Shijingshan District, Beijing, 100049, People’s Republic of China

    Li Zhang, Weixiang Guo, Qi Chen, Xiujun Fan & Ying Zhang

Authors
  1. Li Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weixiang Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiujun Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Enkui Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Enkui Duan.

Additional information

This study was supported by grants from the CAS Knowledge Innovation Program (KSCX2-YW-R-080), the National Basic Research Program of China (grant no. 2006CB944006), and the National Natural Science Foundation of China (grant no. 30770819).

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material

(DOC 28 mb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, L., Guo, W., Chen, Q. et al. Adam12 plays a role during uterine decidualization in mice. Cell Tissue Res 338, 413–421 (2009). https://doi.org/10.1007/s00441-009-0884-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-009-0884-9

Keywords

Search

Navigation