Hostname: page-component-76fb5796d-vfjqv Total loading time: 0 Render date: 2024-04-28T06:22:50.825Z Has data issue: false hasContentIssue false

LEFTY2 expression and localization in rat oviduct during early pregnancy

Published online by Cambridge University Press:  21 December 2010

Martin Eduardo Argañaraz
Affiliation:
Instituto Superior de Investigaciones Biológicas (CONICET-UNT), Chacabuco 461, 4000, Tucumán, Argentina. Institute of Biology, College of Biochemistry, Chemistry and Pharmacy, Universidad Nacional de Tucuman, Chacabuco 461, 3°, Tucumán 4000, Argentina.
Silvana Andrea Apichela
Affiliation:
Instituto Superior de Investigaciones Biológicas (CONICET-UNT), Chacabuco 461, 4000, Tucumán, Argentina. Animal Production Department, College of Agriculture and Zootechnology, Universidad Nacional de Tucuman, Avenida Roca 1900, Tucumán 4000, Argentina.
Dora Cristina Miceli*
Affiliation:
Institute of Biology, College of Biochemistry, Chemistry and Pharmacy, Universidad Nacional de Tucuman, Chacabuco 461, 3°, Tucumán 4000, Argentina. Institute of Biology, College of Biochemistry, Chemistry and Pharmacy, Universidad Nacional de Tucuman, Chacabuco 461, 3°, Tucumán 4000, Argentina.
*
All correspondence to: D.C. Miceli. Institute of Biology, College of Biochemistry, Chemistry and Pharmacy, Universidad Nacional de Tucuman, Chacabuco 461, 3°, Tucumán 4000, Argentina. Tel: +54 381 4247752 ext 7099. Fax: +54 381 4107214. e-mail: doramiceli@fbqf.unt.edu.ar

Summary

In mammals, fertilization and preimplantation embryo development occurs in the oviduct. Cross-talk between the developing embryos and the maternal reproductive tract has been described in such a way as to show that the embryos modulate the physiology and gene expression of the oviduct. Different studies have indicated that transforming growth factor beta (TGF-β) can modulate the oviductal microenvironment and act as an autocrine/paracrine factor on embryo development. LEFTY2, a novel member of the TGF-β superfamily is involved in the negative regulation of other cytokines in this family such as nodal, activin, BMPs, TGF-β1 and Vg1. In previous studies, we have reported that LEFTY2 is differentially expressed in the rat oviduct during pregnancy. In this study, we describe the temporal pattern of LEFTY2 in pregnant and non-pregnant rat oviduct by western blotting, which showed higher levels of LEFTY2 on day 4 of pregnancy, a time at which the embryos are ending their journey along the oviduct. The cellular location of LEFTY2 was assessed by immunohistochemistry, which showed immunolabelling in the cytoplasm and at the apical surface of the oviductal epithelial cells. The oviductal fluid also presented a 26 kDa band, which corresponds to the biologically active form of this protein, at the preimplantation period of pregnancy, indicating LEFTY2 secretion to the lumen. As LEFTY2 is expressed at a high level just before the embryos pass to the uterus, its biological effect might be relevant and significant for the preimplantation stage of embryo development in the oviduct. The fact that embryos do not express LEFTY2 at this stage of development supports this hypothesis.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Argañaraz, M.E., Valdecantos, P.A., Abate, C.M. & Miceli, D.C. (2007). Rat Lefty2 /EBAF gene, isolation and expression analysis in the oviduct during the early pregnancy stage. Genes Genet. Syst. 82, 171–5.CrossRefGoogle ScholarPubMed
Armant, D.R. (2005). Blastocysts don't go it alone. Extrinsic signals fine-tune the intrinsic developmental program of trophoblast cells. Dev. Biol. 280, 260–80.CrossRefGoogle ScholarPubMed
Buhi, W.C., Alvarez, I.M. & Kouba, A.J. (2000). Secreted proteins of the oviduct. Cells Tissues Organs 166, 165–79.CrossRefGoogle ScholarPubMed
Chang, H., Brown, C.W. & Matzuk, M.M. (2002). Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr. Rev. 23, 787823.CrossRefGoogle ScholarPubMed
Chen, C. & Shen, M.M. (2002). Two modes by which Lefty proteins inhibit nodal signaling. Curr. Biol. 14, 618–24.CrossRefGoogle Scholar
Cheng, S.K., Olale, F., Brivanlou, A.H. & Schier, A.F. (2004). Lefty blocks a subset of TGFbeta signals by antagonizing EGF-CFC coreceptors. PLoS Biol. 2, 215–26.CrossRefGoogle ScholarPubMed
Chow, J.F., Lee, K.F., Chan, S.T. & Yeung, W.S. (2001). Quantification of transforming growth factor beta1 (TGFbeta1) mRNA expression in mouse preimplantation embryos and determination of TGFbeta receptor (type I and type II) expression in mouse embryos and reproductive tract. Mol. Hum. Reprod. 7, 1047–56.CrossRefGoogle ScholarPubMed
Cornet, P.B., Picquet, C., Lemoine, P., Osteen, K.G., Bruner-Tran, K.L., Tabibzadeh, S., Courtoy, P.J., Eeckhout, Y., Marbaix, E. & Henriet, P. (2002). Regulation and function of LEFTY-A/EBAF in the human endometrium. mRNA expression during the menstrual cycle, control by progesterone, and effect on matrix metalloproteinases. J. Biol. Chem. 277, 42496–504.CrossRefGoogle Scholar
Drummond, A. & Findlay, J. (2006). Focus on TGF-beta signalling. Reproduction 132, 177–8.CrossRefGoogle ScholarPubMed
Fitzpatrick, R., Casey, O.M., Morris, D., Smith, T., Powell, R. & Sreenan, J.M. (2002). Postmortem stability of RNA isolated from bovine reproductive tissues. Biochim. Biophys. Acta 1574, 10–4.CrossRefGoogle ScholarPubMed
Hamada, H., Meno, C., Watanabe, D. & Saijoh, Y. (2003). Establishment of vertebrate left–right asymmetry. Nat. Rev. Genet. 3, 103–13.CrossRefGoogle Scholar
Hardy, K. & Spanos, S. (2002). Growth factor expression and function in the human and mouse preimplantation embryo. J. Endocrinol. 17, 221–36.CrossRefGoogle Scholar
Jones, G.M., Trounson, A.O., Lolatgis, N. & Wood, C. (1998). Factors affecting the success of human blastocyst development and pregnancy following in vitro fertilization and embryo transfer. Fertil. Steril. 70, 1022–9.CrossRefGoogle ScholarPubMed
Knijn, H.M., Wrenzycki, C., Hendriksen, P.J., Vos, PL., Zeinstra, E.C., Van Der Weijden, G.C., Niemann, H. & Dieleman, S.J. (2005). In vitro and in vivo culture effects on mRNA expression of genes involved in metabolism and apoptosis in bovine embryos. Reprod. Fertil. Dev. 17, 775–84.CrossRefGoogle ScholarPubMed
Larson, R.C., Ignotz, G.G. & Currie, W.B. (1992). Transforming growth factor beta and basic fibroblast growth factor synergistically promote early bovine embryo development during the fourth cell cycle. Mol. Reprod. Dev. 33, 432–5.CrossRefGoogle ScholarPubMed
Lee, Y.L., Lee, K.F., Xu, J.S., He, Q.Y., Chiu, J.F., Lee, W.M., Luk, J.M. & Yeung, W.S.B. (2004). The embryotrophic activity of oviductal cell derived complement C3b and IC3b-a novel function of complement protein in reproduction. J. Biol. Chem. 279, 12763–8.CrossRefGoogle ScholarPubMed
Lee, Y.L., Lee, K.F., Xu, J.S., Kwok, K.L., Luk, J.M., Lee, W.M. & Yeung, W.S. (2003). Embryotrophic factor-3 from human oviductal cells affects the messenger RNA expression of mouse blastocyst. Biol. Reprod. 68, 375–82.CrossRefGoogle ScholarPubMed
Marcondes, F.K., Bianchi, F.J., Tanno, A.P. (2002). Determination of the estrous cycle phases of rats: some helpful considerations. Braz. J. Biol. 62, 609–14.CrossRefGoogle ScholarPubMed
Marquant-Le Guienne, B., Gérard, M., Solari, A. & Thibault, C. (1989). In vitro culture of bovine egg fertilized either in vivo or in vitro. Reprod. Nutr. Dev. 29, 559–68.CrossRefGoogle ScholarPubMed
Meno, C., Saijoh, Y., Fujii, H., Ikeda, M., Yokoyama, T., Yokoyama, M., Toyoda, Y. & Hamada, H. (1996). Left–right asymmetric expression of the TGFβ family member lefty in mouse embryos. Nature 381, 151–5.CrossRefGoogle ScholarPubMed
Mercader, A., Valbuena, D. & Simon, C. (2006). Human embryo culture. Methods Enzymol. 420, 318.CrossRefGoogle ScholarPubMed
Nour, N., Mayer, G., Mort, J.S., Salvas, A., Mbikay, M., Morrison, C.J., Overall, C.M. & Seidah, N.G. (2005). The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases. Mol. Biol. Cell 16, 5215–26CrossRefGoogle ScholarPubMed
Osterlund, C. & Fried, G. (2000). TGFbeta receptor types I and II and the substrate proteins Smad 2 and 3 are present in human oocytes. Mol. Hum. Reprod. 6, 498503.CrossRefGoogle ScholarPubMed
Refaat, B., Amer, S., Ola, B., Chapman, N. & Ledger, W. (2008). The expression of activin-betaA and -betaB subunits, follistatin, and activin type II receptors in fallopian tubes bearing an ectopic pregnancy. J. Clin. Endocrinol. Metab. 93, 293–9.CrossRefGoogle ScholarPubMed
Sakuma, R., Ohnishi, Yi.Y., Meno, C., Fujii, H., Juan, H., Takeuchi, J., Ogura, T., Li, E., Miyazono, K. & Hamada, H. (2002). Inhibition of Nodal signalling by Lefty mediated through interaction with common receptors and efficient diffusion.Genes Cells 7, 401–12.CrossRefGoogle ScholarPubMed
Scamuffa, N., Calvo, F., Chrétien, M., Seidah, N.G. & Khatib, A.M. (2006). FASEB J. 20, 1954–63.CrossRefGoogle Scholar
Shen, M.M. (2007). Nodal signaling, developmental roles and regulation. Development 134, 1023–34.CrossRefGoogle Scholar
Strandell, A., Thorburn, J. & Wallin, A. (2004). The presence of cytokines and growth factors in hydrosalpingeal fluid. J. Assist. Reprod. Genet. 21, 241–7.CrossRefGoogle ScholarPubMed
Tabibzadeh, S., Lessey, B. & Satyaswaroop, P.G. (1998). Temporal and site-specific expression of transforming growth factor-beta4 in human endometrium. Mol. Hum. Reprod. 4, 595602.CrossRefGoogle ScholarPubMed
Tabibzadeh, S., Mason, J.M., Shea, W., Cai, Y., Murray, M.J. & Lessey, B. (2000). Dysregulated expression of EBAF a novel molecular defect in the endometria of patients with infertility. J. Clin. Endocrinol. Metab. 85, 2526–36.Google ScholarPubMed
Tang, M., Mikhailik, A., Pauli, I., Giudice, L.C., Fazleabas, AT., Tulac, S., Carson, D.D., Kaufman, D.G., Barbier, C., Creemers, J.W. & Tabibzadeh, S. (2005a). Decidual differentiation of stromal cells promotes pc5/6 expression and lefty processing. Endocrinology 146, 5313–20.CrossRefGoogle Scholar
Tang, M., Xu, Y., Julian, J., Carson, D. & Tabibzadeh, S. (2005b. Lefty is expressed in mouse endometrium in estrous cycle and preimplantation period. Hum. Reprod. 20, 872–80.CrossRefGoogle Scholar
Ulloa, L., Creemers, J.W., Roy, S., Liu, S., Mason, J. & Tabibzadeh, S. (2001). Lefty proteins exhibit unique processing and activate the MAPK pathway. J. Biol. Chem. 276, 21387–96.CrossRefGoogle ScholarPubMed
Valdecantos, P.A., Argañaraz, M.E., Abate, C.M. & Miceli, DC. (2004). RNA fingerprinting using RAP-PCR identifies an EBAF homologue mRNA differentially expressed in rat oviduct. Biocell 28, 287–97.CrossRefGoogle ScholarPubMed
Wolf, E., Arnold, G.J., Bauersachs, S., Beier, H.M., Blum, H., Einspanier, R., Frohlich, T., Herrler, A., Hiendleder, S., Kölle, S., Prelle, K., Reichenbach, H.D., Stojkovic, M., Wenigerkind, H. & Sinowatz, F. (2003). Embryo–maternal communication in bovine-strategies for deciphering a complex cross-talk. Reprod. Domest. Anim. 38, 276–89.CrossRefGoogle ScholarPubMed
Yeung, W.S.B., Lee, K.F. & Xu, J.S. (2002). The oviduct and development of preimplantation embryo. Reprod. Med. Rev. 10, 2144.CrossRefGoogle Scholar
Zhao, Y., Chegini, N. & Flanders, KC. (1994). Human fallopian tube expresses transforming growth factor (TGF beta) isoforms, TGF beta type I-III receptor messenger ribonucleic acid and protein, and contains [125I]TGF beta-binding sites. J. Clin. Endocrinol. Metab. 79, 1177–84.Google ScholarPubMed