Hostname: page-component-7dd5485656-c8zdz Total loading time: 0 Render date: 2025-10-31T17:12:15.732Z Has data issue: false hasContentIssue false
  • English
  • Français

Genes of the transforming growth factor-beta signalling pathway are associated with pre-implantation embryonic development in cattle

Published online by Cambridge University Press:  12 June 2012

Geng Li ,
Karam Khateeb ,
Erin Schaeffer ,
Bao Zhang  and
Hasan Khatib
Geng Li
Affiliation:
College of Animal Science and Technology, China Agricultural University, Beijing 100193, China Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA
Karam Khateeb
Affiliation:
Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA
Erin Schaeffer
Affiliation:
Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA
Bao Zhang
Affiliation:
College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China
Hasan Khatib*
Affiliation:
Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA
*
*For correspondence; e-mail: hkhatib@wisc.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

One of the main factors affecting cattle fertility is pre-implantation development of the bovine embryo, which is a complex process regulated by various signal-transduction pathways. The transforming growth factor-β (TGF-β) signalling system, which is responsible for many biological processes including cell proliferation, differentiation and apoptosis, also is involved in embryo development. We hypothesized that altered expression of TGF-β genes in pre-implantation bovine embryos is associated with morphological abnormalities of these embryos. To test this hypothesis, we produced embryos in vitro and classified them at the blastocyst stage as either normally developed blastocysts or degenerates (growth-arrested embryos). The expression patterns of 25 genes from the TGF-β pathway were assessed using quantitative real time PCR. Ten genes showed differential expression between the two embryo groups, four genes displayed similar expressional profiles, and 11 genes had no detectable expression. An altered expression profile was statistically significant for 10 of the 14 expressed genes, and all were up-regulated in degenerate embryos vs. blastocysts. Furthermore, genomic association analysis of the cows from which embryos were produced revealed a significant association of ID3 and BMP4 polymorphisms—two of the most significant differentially expressed genes—with fertilization rate and blastocyst rate, respectively. Taken together, we conclude that TGF-β pathway genes, especially BMP4 and ID3 play a vital function in the regulation of pre-implantation embryo development at both embryo and maternal levels. Hence, these genes may be suitable as genetic markers for embryo development and fertility in cattle.

Keywords

Transforming growth factor-βbovinepre-implantation embryoembryo survival

Information

Type
Research Article
Information
Journal of Dairy Research , Volume 79 , Issue 3 , August 2012 , pp. 310 - 317
Copyright
Copyright © Proprietors of Journal of Dairy Research 2012

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.)

Article purchase

Temporarily unavailable

References

Assou, S, Boumela, I, Haouzi, D, Anahory, T, Dechaud, H, De Vos, J & Hamamah, S 2010 Dynamic changes in gene expression during human early embryo development: from fundamental aspects to clinical applications. Human Reproduction Update 17 272–290 Google Scholar
Chow, JF, Lee, KF, Chan, ST & Yeung, WS 2001 Quantification of transforming growth factor beta1 (TGFbeta1) mRNA expression in mouse pre-implantation embryos and determination of TGFbeta receptor (type I and type II) expression in mouse embryos and reproductive tract. Molecular Humam Reproduction 7 1047–1056 CrossRefGoogle Scholar
Driver, AM, Huang, W, Gajic, S, Monson, RL, Rosa, GJ & Khatib, H 2009 Short communication: Effects of the progesterone receptor variants on fertility traits in cattle. Journal of Dairy Science 92 4082–4085 CrossRefGoogle ScholarPubMed
Fatehi, AN, van den Hurk, R, Colenbrander, B, Daemen, AJ, van Tol, HT, Monteiro, RM, Roelen, BA & Bevers, MM 2005 Expression of bone morphogenetic protein 2 (BMP2), BMP4 and BMP receptors in the bovine ovary but absence of effects of BMP2 and BMP4 during IVM on bovine oocyte nuclear maturation and subsequent embryo development. Theriogenology 63 872–889 CrossRefGoogle ScholarPubMed
Fenton, TR & Gout, IT 2010 Functions and regulation of the 70 kDa ribosomal S6 kinases. International Journal of Biochemistry and Cell Biology 43 47–59 Google Scholar
Heinke, J, Wehofsits, L, Zhou, Q, Zoeller, C, Baar, KM, Helbing, T, Laib, A, Augustin, H, Bode, C, Patterson, C & Moser, M 2008 BMPER is an endothelial cell regulator and controls bone morphogenetic protein-4-dependent angiogenesis. Circulation Research 103 804–812 CrossRefGoogle ScholarPubMed
Heldin, CH, Miyazono, K & ten Dijke, P 1997 TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 390 465–471 Google Scholar
Hogg, K, Etherington, SL, Young, JM, McNeilly, AS & Duncan, WC 2010 Inhibitor of differentiation (Id) genes are expressed in the steroidogenic cells of the ovine ovary and are differentially regulated by members of the transforming growth factor-beta family. Endocrinology 151 1247–1256 Google Scholar
Huang, W & Khatib, H 2010 Comparison of transcriptomic landscapes of bovine embryos using RNA-Seq. BMC Genomics 11 711 CrossRefGoogle ScholarPubMed
Huang, W, Kirkpatrick, BW, Rosa, GJ & Khatib, H 2010a A genome-wide association study using selective DNA pooling identifies candidate markers for fertility in Holstein cattle. Animal Genetics 41 570–578 CrossRefGoogle ScholarPubMed
Huang, W, Yandell, BS & Khatib, H 2010b Transcriptomic profiling of bovine IVF embryos revealed candidate genes and pathways involved in early embryonic development. BMC Genomics 11 23 CrossRefGoogle ScholarPubMed
James, D, Levine, AJ, Besser, D & Hemmati-Brivanlou, A 2005 TGFbeta/activin/nodal signalling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132 1273–1282 Google Scholar
Jones, RL, Stoikos, C, Findlay, JK & Salamonsen, LA 2006 TGF-beta superfamily expression and actions in the endometrium and placenta. Reproduction 132 217–232 CrossRefGoogle ScholarPubMed
Kayamori, T, Kosaka, N, Miyamoto, A & Shimizu, T 2009 The differential pathways of bone morphogenetic protein (BMP)-4 and -7 in the suppression of the bovine granulosa cell apoptosis. Molecular and Cellular Biochemistry 323 161–168 Google Scholar
Khatib, H, Huang, W, Mikheil, D, Schutzkus, V & Monson, RL 2009a Effects of signal transducer and activator of transcription (STAT) genes STAT1 and STAT3 genotypic combinations on fertilization and embryonic survival rates in Holstein cattle. Journal of Dairy Science 92 6186–6191 CrossRefGoogle ScholarPubMed
Khatib, H, Huang, W, Wang, X, Tran, AH, Bindrim, AB, Schutzkus, V, Monson, RL & Yandell, BS 2009b Single gene and gene interaction effects on fertilization and embryonic survival rates in cattle. Journal of Dairy Science 92 2238–2247 Google Scholar
Khatib, H, Maltecca, C, Monson, RL, Schutzkus, V, Wang, X & Rutledge, JJ 2008a The fibroblast growth factor 2 gene is associated with embryonic mortality in cattle. Journal of Animal Science 86 2063–2067 Google Scholar
Khatib, H, Monson, RL, Schutzkus, V, Kohl, DM, Rosa, GJ & Rutledge, JJ 2008b Mutations in the STAT5A gene are associated with embryonic survival and milk composition in cattle. Journal of Dairy Science 91 784–793 Google Scholar
Koide, Y, Kiyota, T, Tonganunt, M, Pinkaew, D, Liu, Z, Kato, Y, Hutadilok-Towatana, N, Phongdara, A & Fujise, K 2009 Embryonic lethality of fortilin-null mutant mice by BMP-pathway overactivation. Biochimica et Biophysica Acta 1790 326–338 CrossRefGoogle ScholarPubMed
Laporta, J, Driver, A & Khatib, H 2011 Short communication: expression and alternative splicing of POU1F1 pathway genes in pre-implantation bovine embryos. Journal of Dairy Science 94 4220–4223 Google Scholar
La Rosa, I, Camargo, LS, Pereira, MM, Fernandez-Martin, R, Paz, DA & Salamone, DF 2011 Effects of bone morphogenic protein 4 (BMP4) and its inhibitor, Noggin, on in vitro maturation and culture of bovine pre-implantation embryos. Reproductive Biology and Endocrinology 9 18 CrossRefGoogle Scholar
Li, CW & Ge, W 2011 Spatiotemporal expression of bone morphogenetic protein family ligands and receptors in the zebrafish ovary: a potential paracrine-signalling mechanism for oocyte-follicle cell communication. Biology of Reproduction 85 977–986 CrossRefGoogle ScholarPubMed
Livak, KJ & Schmittgen, TD 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25 402–408 Google Scholar
Lucy, MC 2007 Fertility in high-producing dairy cows: reasons for decline and corrective strategies for sustainable improvement. Society of Reproduction and Fertility Supplement 64 237–254 Google Scholar
Marteil, G, Richard-Parpaillon, L & Kubiak, JZ 2009 Role of oocyte quality in meiotic maturation and embryonic development. Reproductive Biology 9 203–224 Google Scholar
Massague, J, Seoane, J & Wotton, D 2005 Smad transcription factors. Genes and Development 19 2783–2810 Google Scholar
Miyazono, K & Miyazawa, K 2002 Id: a target of BMP signalling. Science STKE 151 pe40 Google Scholar
Moser, M, Binder, O, Wu, Y, Aitsebaomo, J, Ren, R, Bode, C, Bautch, VL, Conlon, FL & Patterson, C 2003 BMPER, a novel endothelial cell precursor-derived protein, antagonizes bone morphogenetic protein signalling and endothelial cell differentiation. Molecular and Cellular Biology 23 5664–5679 CrossRefGoogle ScholarPubMed
Murphy-Ullrich, JE & Poczatek, M 2000 Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine and Growth Factor Reviews 11 59–69 CrossRefGoogle ScholarPubMed
Nilsson, EE & Skinner, MK 2003 Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biology of Reproduction 69 1265–1272 Google Scholar
Norton, JD 2000 ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. Journal of Cell Science 113 3897–3905 CrossRefGoogle ScholarPubMed
Otsuka, F, McTavish, KJ & Shimasaki, S 2011 Integral role of GDF-9 and BMP-15 in ovarian function. Molecular Reproduction and Development 78 9–21 Google Scholar
Pant, D & Keefer, CL 2009 Expression of pluripotency-related genes during bovine inner cell mass explant culture. Cloning Stem Cells 11 355–365 CrossRefGoogle ScholarPubMed
Rizos, D, Ward, F, Duffy, P, Boland, MP & Lonergan, P 2002 Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo: implications for blastocyst yield and blastocyst quality. Molecular Reproduction and Development 61 234–248 Google Scholar
Rodriguez-Zas, SL, Schellander, K & Lewin, HA 2008 Biological interpretations of transcriptomic profiles in mammalian oocytes and embryos. Reproduction 135 129–139 Google Scholar
Royal, M, Mann, GE & Flint, AP 2000 Strategies for reversing the trend towards subfertility in dairy cattle. Veterinary Journal 160 53–60 Google Scholar
Santibanez, JF, Quintanilla, M & Bernabeu, C 2011 TGF-beta/TGF-beta receptor system and its role in physiological and pathological conditions. Clinical Science 121 233–251 CrossRefGoogle ScholarPubMed
Sheldon, IM, Wathes, DC & Dobson, H 2006 The management of bovine reproduction in elite herds. Veterinary Journal 171 70–78 CrossRefGoogle ScholarPubMed
Shimasaki, S, Moore, RK, Otsuka, F & Erickson, GF 2004 The bone morphogenetic protein system in mammalian reproduction. Endocrine Reviews 25 72–101 Google Scholar
Shimasaki, S, Zachow, RJ, Li, D, Kim, H, Iemura, S, Ueno, N, Sampath, K, Chang, & Erickson, GF 1999 A functional bone morphogenetic protein system in the ovary. Proceedings of the National Academy of Sciences of the United States of America 96 7282–7287 CrossRefGoogle ScholarPubMed
Shimizu, T, Yokoo, M, Miyake, Y, Sasada, H & Sato, E 2004 Differential expression of bone morphogenetic protein 4–6 (BMP-4, -5, and -6) and growth differentiation factor-9 (GDF-9) during ovarian development in neonatal pigs. Domestic Animal Endocrinology 27 397–405 CrossRefGoogle ScholarPubMed
Shook, GE 2006 Major advances in determining appropriate selection goals. Journal of Dairy Science 89 1349–1361 Google Scholar
Stitzel, ML & Seydoux, G 2007 Regulation of the oocyte-to-zygote transition. Science 316 407–408 Google Scholar
Tanwar, PS & McFarlane, JR 2011 Dynamic expression of bone morphogenetic protein 4 in reproductive organs of female mice. Reproduction 142 573–579 Google Scholar
Trombly, DJ, Woodruff, TK & Mayo, KE 2009 Roles for transforming growth factor beta superfamily proteins in early folliculogenesis. Seminars in Reproductive Medicine 27 14–23 CrossRefGoogle ScholarPubMed
VanRaden, PM, Sanders, AH, Tooker, ME, Miller, RH, Norman, HD, Kuhn, MT & Wiggans, GR 2004 Development of a national genetic evaluation for cow fertility. Journal of Dairy Science 87 2285–2292 CrossRefGoogle ScholarPubMed
Wang, QT, Piotrowska, K, Ciemerych, MA, Milenkovic, L, Scott, MP, Davis, RW & Zernicka-Goetz, M 2004 A genome-wide study of gene activity reveals developmental signalling pathways in the pre-implantation mouse embryo. Developmental Cell 6 133–144 Google Scholar
Wang, X, Schutzkus, V, Huang, W, Rosa, GJ & Khatib, H 2009 Analysis of segregation distortion and association of the bovine FGF2 with fertilization rate and early embryonic survival. Animal Genetics 40 722–728 Google Scholar
Yokota, Y & Mori, S 2002 Role of Id family proteins in growth control. Journal of Cellular Physiology 190 21–28 Google Scholar
Zhang, B, Penagaricano, F, Driver, A, Chen, H & Khatib, H 2011 Differential expression of heat shock protein genes and their splice variants in bovine pre-implantation embryos. Journal of Dairy Science 94 4174–4182 Google Scholar
Zhang, Y, Yang, Z & Wu, J 2007 Signalling pathways and pre-implantation development of mammalian embryos. FEBS Journal 274 4349–4359 Google Scholar
Zolnierowicz, S 2000 Type 2A protein phosphatase, the complex regulator of numerous signalling pathways. Biochemical Pharmacology 60 1225–1235 CrossRefGoogle Scholar
Supplementary material: File

Li supplementary material

Appendix

Download Li supplementary material(File)
File 92.2 KB