Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

The requirement for protein kinase C delta (PRKCD) during preimplantation bovine embryo development

Qi-En Yang A B , Manabu Ozawa B D , Kun Zhang B E , Sally E. Johnson B C and Alan D. Ealy B C F

A Key Laboratory of Adaption and Evolution of Plateau Biota, Northwest Plateau Institute of Biology, Chinese Academy of Sciences, Xining, Qinghai 810001, China.

B Department of Animal Sciences, University of Florida, Gainesville, FL 32611, USA.

C Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, 175 W. Campus Drive, Blacksburg, VA 24061, USA.

D Present address: Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.

E Present address: Department of Animal Science, Michigan State University, East Lansing, MI 48824-1225, USA.

F Corresponding author. Email: ealy@vt.edu

Reproduction, Fertility and Development 28(4) 482-490 http://dx.doi.org/10.1071/RD14160
Submitted: 17 May 2014  Accepted: 17 July 2014   Published: 13 August 2014

Abstract

Protein kinase C (PKC) delta (PRKCD) is a member of the novel PKC subfamily that regulates gene expression in bovine trophoblast cells. Additional functions for PRKCD in early embryonic development in cattle have not been fully explored. The objectives of this study were to describe the expression profile of PRKCD mRNA in bovine embryos and to examine its biological roles during bovine embryo development. Both PRKCD mRNA and protein are present throughout early embryo development and increases in mRNA abundance are evident at morula and blastocyst stages. Phosphorylation patterns are consistent with detection of enzymatically active PRKCD in bovine embryos. Exposure to a pharmacological inhibitor (rottlerin) during early embryonic development prevented development beyond the eight- to 16-cell stage. Treatment at or after the 16-cell stage reduced blastocyst development rates, total blastomere numbers and inner cell mass-to-trophoblast cell ratio. Exposure to the inhibitor also decreased basal interferon tau (IFNT) transcript abundance and abolished fibroblast growth factor-2 induction of IFNT expression. Furthermore, trophoblast adhesion and proliferation was compromised in hatched blastocysts. These observations provide novel insights into PRKCD mRNA expression profiles in bovine embryos and provide evidence for PRKCD-dependent regulation of embryonic development, gene expression and post-hatching events.

Additional keywords: embryonic development, embryonic gene expression, post-hatching development.


References

Chen, C. L., Chan, P. C., Wang, S. H., Pan, Y. R., and Chen, H. C. (2010). Elevated expression of protein kinase C delta induces cell scattering upon serum deprivation. J. Cell Sci. 123, 2901–2913.
Elevated expression of protein kinase C delta induces cell scattering upon serum deprivation.CrossRef | 1:CAS:528:DC%2BC3cXhtlars7jM&md5=0d6ccb12bfbb32d9ea3b71756ea88b56CAS | 20682636PubMed | open url image1

Cooke, F. N., Pennington, K. A., Yang, Q., and Ealy, A. D. (2009). Several fibroblast growth factors are expressed during pre-attachment bovine conceptus development and regulate interferon-tau expression from trophectoderm. Reproduction 137, 259–269.
Several fibroblast growth factors are expressed during pre-attachment bovine conceptus development and regulate interferon-tau expression from trophectoderm.CrossRef | 1:CAS:528:DC%2BD1MXovV2ksLw%3D&md5=a926bcfc8deffd46c524fe00181fca3cCAS | 18996977PubMed | open url image1

Davies, S. P., Reddy, H., Caivano, M., and Cohen, P. (2000). Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351, 95–105.
Specificity and mechanism of action of some commonly used protein kinase inhibitors.CrossRef | 1:CAS:528:DC%2BD3cXnslWltrY%3D&md5=8d3e9410704217094a4c5032d10dec25CAS | 10998351PubMed | open url image1

Dehghani, H., and Hahnel, A. C. (2005). Expression profile of protein kinase C isozymes in preimplantation mouse development. Reproduction 130, 441–451.
Expression profile of protein kinase C isozymes in preimplantation mouse development.CrossRef | 1:CAS:528:DC%2BD2MXhtFent7rN&md5=7500d0ab1160e7c0c94f71f23142c820CAS | 16183862PubMed | open url image1

Dehghani, H., Reith, C., and Hahnel, A. C. (2005). Subcellular localisation of protein kinase C delta and epsilon affects transcriptional and post-transcriptional processes in four-cell mouse embryos. Reproduction 130, 453–465.
Subcellular localisation of protein kinase C delta and epsilon affects transcriptional and post-transcriptional processes in four-cell mouse embryos.CrossRef | 1:CAS:528:DC%2BD2MXhtFent7rO&md5=b6b77e8abaeb8a61f851fa873823f48dCAS | 16183863PubMed | open url image1

Diskin, M. G., and Morris, D. G. (2008). Embryonic and early foetal losses in cattle and other ruminants. Reprod. Domest. Anim. 43, 260–267.
Embryonic and early foetal losses in cattle and other ruminants.CrossRef | 18638133PubMed | open url image1

Dobbs, K. B., Khan, F. A., Sakatani, M., Moss, J. I., Ozawa, M., Ealy, A. D., and Hansen, P. J. (2013). Regulation of pluripotency of inner cell mass and growth and differentiation of trophectoderm of the bovine embryo by colony-stimulating factor 2. Biol. Reprod. 89, 141.
Regulation of pluripotency of inner cell mass and growth and differentiation of trophectoderm of the bovine embryo by colony-stimulating factor 2.CrossRef | 24198123PubMed | open url image1

Driver, A. M., Penagaricano, F., Huang, W., Ahmad, K. R., Hackbart, K. S., Wiltbank, M. C., and Khatib, H. (2012). RNA-Seq analysis uncovers transcriptomic variations between morphologically similar in vivo- and in vitro-derived bovine blastocysts. BMC Genomics 13, 118.
RNA-Seq analysis uncovers transcriptomic variations between morphologically similar in vivo- and in vitro-derived bovine blastocysts.CrossRef | 1:CAS:528:DC%2BC38XovVeitbw%3D&md5=4e5beafcc52ff3baaed386659da5604aCAS | 22452724PubMed | open url image1

Ealy, A. D., and Yang, Q. E. (2009). Control of interferon-tau expression during early pregnancy in ruminants. Am. J. Reprod. Immunol. 61, 95–106.
Control of interferon-tau expression during early pregnancy in ruminants.CrossRef | 1:CAS:528:DC%2BD1MXislOhu7s%3D&md5=c27c46a6f499f53280b6ab1b99cfc0a6CAS | 19143673PubMed | open url image1

Eckert, J. J., McCallum, A., Mears, A., Rumsby, M. G., Cameron, I. T., and Fleming, T. P. (2004). Specific PKC isoforms regulate blastocoel formation during mouse preimplantation development. Dev. Biol. 274, 384–401.
Specific PKC isoforms regulate blastocoel formation during mouse preimplantation development.CrossRef | 1:CAS:528:DC%2BD2cXnvVyqsrw%3D&md5=d93dafc70a085524f2de7a223193d44dCAS | 15385166PubMed | open url image1

Eckert, J. J., McCallum, A., Mears, A., Rumsby, M. G., Cameron, I. T., and Fleming, T. P. (2005). Relative contribution of cell-contact pattern, specific PKC isoforms and gap-junctional communication in tight-junction assembly in the mouse early embryo. Dev. Biol. 288, 234–247.
Relative contribution of cell-contact pattern, specific PKC isoforms and gap-junctional communication in tight-junction assembly in the mouse early embryo.CrossRef | 1:CAS:528:DC%2BD2MXht1OltbzM&md5=b921d6ed2767c09a39bbc1318d75d274CAS | 16271712PubMed | open url image1

Fear, J. M., and Hansen, P. J. (2011). Developmental changes in expression of genes involved in regulation of apoptosis in the bovine preimplantation embryo. Biol. Reprod. 84, 43–51.
Developmental changes in expression of genes involved in regulation of apoptosis in the bovine preimplantation embryo.CrossRef | 1:CAS:528:DC%2BC3MXlvVegtbg%3D&md5=240a561ef769edbd921ae2215c5e8a26CAS | 20811013PubMed | open url image1

Gad, A., Hoelker, M., Besenfelder, U., Havlicek, V., Cinar, U., Rings, F., Held, E., Dufort, I., Sirard, M. A., Schellander, K., and Tesfaye, D. (2012). Molecular mechanisms and pathways involved in bovine embryonic genome activation and their regulation by alternative in vivo and in vitro culture conditions. Biol. Reprod. 87, 100.
Molecular mechanisms and pathways involved in bovine embryonic genome activation and their regulation by alternative in vivo and in vitro culture conditions.CrossRef | 22811576PubMed | open url image1

Griner, E. M., and Kazanietz, M. G. (2007). Protein kinase C and other diacylglycerol effectors in cancer. Nat. Rev. Cancer 7, 281–294.
Protein kinase C and other diacylglycerol effectors in cancer.CrossRef | 1:CAS:528:DC%2BD2sXjtlyhtLg%3D&md5=e469d579e9e5fddbf089067d837a2530CAS | 17384583PubMed | open url image1

Gschwendt, M., Muller, H. J., Kielbassa, K., Zang, R., Kittstein, W., Rincke, G., and Marks, F. (1994). Rottlerin, a novel protein kinase inhibitor. Biochem. Biophys. Res. Commun. 199, 93–98.
Rottlerin, a novel protein kinase inhibitor.CrossRef | 1:CAS:528:DyaK2cXitlyqsLc%3D&md5=d3f44944f17fa3373c21a58444c8a13bCAS | 8123051PubMed | open url image1

Iwasaki, S., Yoshiba, N., Ushijima, H., Watanabe, S., and Nakahara, T. (1990). Morphology and proportion of inner cell mass of bovine blastocysts fertilized in vitro and in vivo. J. Reprod. Fertil. 90, 279–284.
Morphology and proportion of inner cell mass of bovine blastocysts fertilized in vitro and in vivo.CrossRef | 1:STN:280:DyaK3M%2FjvFSlsw%3D%3D&md5=4cbc084270da5db7b8450fa294f1659aCAS | 2231548PubMed | open url image1

Kalive, M., Faust, J. J., Koeneman, B. A., and Capco, D. G. (2010). Involvement of the PKC family in regulation of early development. Mol. Reprod. Dev. 77, 95–104.
| 1:CAS:528:DC%2BD1MXhsF2jurnM&md5=a1a0dd19b6924b58d1996d8bc75e16edCAS | 19777543PubMed | open url image1

Kikkawa, U., Matsuzaki, H., and Yamamoto, T. (2002). Protein kinase C delta (PKC delta): activation mechanisms and functions. J. Biochem. 132, 831–839.
Protein kinase C delta (PKC delta): activation mechanisms and functions.CrossRef | 1:CAS:528:DC%2BD3sXhtlGjtb4%3D&md5=c0cde3e3f08c0c60aed5b46d1f00bbf6CAS | 12473183PubMed | open url image1

Knijn, H. M., Gjorret, J. O., Vos, P. L., Hendriksen, P. J., van der Weijden, B. C., Maddox-Hyttel, P., and Dieleman, S. J. (2003). Consequences of in vivo development and subsequent culture on apoptosis, cell number and blastocyst formation in bovine embryos. Biol. Reprod. 69, 1371–1378.
Consequences of in vivo development and subsequent culture on apoptosis, cell number and blastocyst formation in bovine embryos.CrossRef | 1:CAS:528:DC%2BD3sXnsV2nsbs%3D&md5=268a0b2da13762ed3ce447ba3c43e62dCAS | 12826584PubMed | open url image1

Kontny, E., Kurowska, M., Szczepanska, K., and Maslinski, W. (2000). Rottlerin, a PKC isozyme-selective inhibitor, affects signalling events and cytokine production in human monocytes. J. Leukoc. Biol. 67, 249–258.
| 1:CAS:528:DC%2BD3cXkvVygtLY%3D&md5=8a5c4aa3b2ca2d2d8a1762897f778db9CAS | 10670587PubMed | open url image1

Koot, Y. E., Teklenburg, G., Salker, M. S., Brosens, J. J., and Macklon, N. S. (2012). Molecular aspects of implantation failure. Biochim. Biophys. Acta 1822, 1943–1950.
Molecular aspects of implantation failure.CrossRef | 1:CAS:528:DC%2BC38XptFahu7w%3D&md5=cfb9e4949980444bf2a100cf424e629cCAS | 22683339PubMed | open url image1

Leitges, M., Mayr, M., Braun, U., Mayr, U., Li, C., Pfister, G., Ghaffari-Tabrizi, N., Baier, G., Hu, Y., and Xu, Q. (2001). Exacerbated vein graft arteriosclerosis in protein kinase Cdelta-null mice. J. Clin. Invest. 108, 1505–1512.
Exacerbated vein graft arteriosclerosis in protein kinase Cdelta-null mice.CrossRef | 1:CAS:528:DC%2BD3MXosVyrurY%3D&md5=c972763cda9218869e1111d47dba5135CAS | 11714742PubMed | open url image1

Liu, H., Wu, Z., Shi, X., Li, W., Liu, C., Wang, D., Ye, X., Liu, L., Na, J., Cheng, H., and Chen, L. (2013). Atypical PKC, regulated by Rho GTPases and Mek/Erk, phosphorylates Ezrin during eight-cell embryo compaction. Dev. Biol. 375, 13–22.
Atypical PKC, regulated by Rho GTPases and Mek/Erk, phosphorylates Ezrin during eight-cell embryo compaction.CrossRef | 1:CAS:528:DC%2BC3sXit1Kisrc%3D&md5=613b4308402248905ee7ecc4b55996e8CAS | 23313818PubMed | open url image1

Loureiro, B., Bonilla, L., Block, J., Fear, J. M., Bonilla, A. Q., and Hansen, P. J. (2009). Colony-stimulating factor 2 (CSF-2) improves development and post-transfer survival of bovine embryos produced in vitro. Endocrinology 150, 5046–5054.
Colony-stimulating factor 2 (CSF-2) improves development and post-transfer survival of bovine embryos produced in vitro.CrossRef | 1:CAS:528:DC%2BD1MXhsVCht7bF&md5=65e3733d1dd721d9af4ccb977214a029CAS | 19797121PubMed | open url image1

Michael, D. D., Alvarez, I. M., Ocon, O. M., Powell, A. M., Talbot, N. C., Johnson, S. E., and Ealy, A. D. (2006). Fibroblast growth factor-2 is expressed by the bovine uterus and stimulates interferon-tau production in bovine trophectoderm. Endocrinology 147, 3571–3579.
Fibroblast growth factor-2 is expressed by the bovine uterus and stimulates interferon-tau production in bovine trophectoderm.CrossRef | 1:CAS:528:DC%2BD28XmtlOrsbk%3D&md5=56f4fba67b3af9b3a0e387b15eb9453eCAS | 16574787PubMed | open url image1

Natale, D. R., Paliga, A. J., Beier, F., D’Souza, S. J., and Watson, A. J. (2004). p38 MAPK signalling during murine preimplantation development. Dev. Biol. 268, 76–88.
p38 MAPK signalling during murine preimplantation development.CrossRef | 1:CAS:528:DC%2BD2cXitFKgurY%3D&md5=5e4d740c75d413abc1e7452e00ba249bCAS | 15031106PubMed | open url image1

Ohsugi, M., Ohsawa, T., and Yamamura, H. (1993). Involvement of protein kinase C in nuclear migration during compaction and the mechanism of the migration: analyses in two-cell mouse embryos. Dev. Biol. 156, 146–154.
Involvement of protein kinase C in nuclear migration during compaction and the mechanism of the migration: analyses in two-cell mouse embryos.CrossRef | 1:CAS:528:DyaK3sXitV2qtbY%3D&md5=6895877fa88bde3b9bb2430319eeae0bCAS | 8449365PubMed | open url image1

Ozawa, M., Yang, Q. E., and Ealy, A. D. (2013). The expression of fibroblast growth factor receptors during early bovine conceptus development and pharmacological analysis of their actions on trophoblast growth in vitro. Reproduction 145, 191–201.
The expression of fibroblast growth factor receptors during early bovine conceptus development and pharmacological analysis of their actions on trophoblast growth in vitro.CrossRef | 1:CAS:528:DC%2BC3sXjtlOnt74%3D&md5=499882e8c1c301cf0483b329d39d4d67CAS | 23241344PubMed | open url image1

Paliga, A. J., Natale, D. R., and Watson, A. J. (2005). p38 mitogen-activated protein kinase (MAPK) first regulates filamentous actin at the 8–16-cell stage during preimplantation development. Biol. Cell 97, 629–640.
p38 mitogen-activated protein kinase (MAPK) first regulates filamentous actin at the 8–16-cell stage during preimplantation development.CrossRef | 1:CAS:528:DC%2BD2MXmsFCiu7g%3D&md5=a03dc546cd167d97183b2286daff2da7CAS | 15850458PubMed | open url image1

Pauken, C. M., and Capco, D. G. (1999). Regulation of cell adhesion during embryonic compaction of mammalian embryos: roles for PKC and beta-catenin. Mol. Reprod. Dev. 54, 135–144.
Regulation of cell adhesion during embryonic compaction of mammalian embryos: roles for PKC and beta-catenin.CrossRef | 1:CAS:528:DyaK1MXmtVSktb4%3D&md5=f691fad6b8219a87734e716f5eddf9c8CAS | 10471473PubMed | open url image1

Pauken, C. M., and Capco, D. G. (2000). The expression and stage-specific localisation of protein kinase C isotypes during mouse preimplantation development. Dev. Biol. 223, 411–421.
The expression and stage-specific localisation of protein kinase C isotypes during mouse preimplantation development.CrossRef | 1:CAS:528:DC%2BD3cXksFeqs70%3D&md5=40f493aebfa853c4fe331075c68501aeCAS | 10882525PubMed | open url image1

Purcell, S. H., Cantlon, J. D., Wright, C. D., Henkes, L. E., Seidel, G. E., and Anthony, R. V. (2009). The involvement of proline-rich 15 in early conceptus development in sheep. Biol. Reprod. 81, 1112–1121.
The involvement of proline-rich 15 in early conceptus development in sheep.CrossRef | 1:CAS:528:DC%2BD1MXhsV2lt7jP&md5=28c7012392a4508cab2468045bb6cd60CAS | 19605793PubMed | open url image1

Robert, C., McGraw, S., Massicotte, L., Pravetoni, M., Gandolfi, F., and Sirard, M. A. (2002). Quantification of housekeeping transcript levels during the development of bovine preimplantation embryos. Biol. Reprod. 67, 1465–1472.
Quantification of housekeeping transcript levels during the development of bovine preimplantation embryos.CrossRef | 1:CAS:528:DC%2BD38Xot1Kjs78%3D&md5=f36b2e476d7bad869966f6b6a8165856CAS | 12390877PubMed | open url image1

Rossant, J. (2004). Lineage development and polar asymmetries in the peri-implantation mouse blastocyst. Semin. Cell Dev. Biol. 15, 573–581.
Lineage development and polar asymmetries in the peri-implantation mouse blastocyst.CrossRef | 15271303PubMed | open url image1

Steinberg, S. F. (2008). Structural basis of protein kinase C isoform function. Physiol. Rev. 88, 1341–1378.
Structural basis of protein kinase C isoform function.CrossRef | 1:CAS:528:DC%2BD1cXhtlGgtbnJ&md5=f69acbc968bffe9fe2323661c61042aeCAS | 18923184PubMed | open url image1

Vigneault, C., Gravel, C., Vallee, M., McGraw, S., and Sirard, M. A. (2009). Unveiling the bovine embryo transcriptome during the maternal-to-embryonic transition. Reproduction 137, 245–257.
Unveiling the bovine embryo transcriptome during the maternal-to-embryonic transition.CrossRef | 1:CAS:528:DC%2BD1MXovV2ksL8%3D&md5=761af5525f7d639a8309b6edda3d93a1CAS | 18987256PubMed | open url image1

Watson, A. J., and Barcroft, L. C. (2001). Regulation of blastocyst formation. Front. Biosci. 6, d708–d730.
Regulation of blastocyst formation.CrossRef | 1:CAS:528:DC%2BD3MXlslKhtL4%3D&md5=ce195efc94da58a5cd44c20c249a84e9CAS | 11333210PubMed | open url image1

Welman, A., Griffiths, J. R., Whetton, A. D., and Dive, C. (2007). Protein kinase C delta is phosphorylated on five novel Ser/Thr sites following inducible overexpression in human colorectal cancer cells. Protein Sci. 16, 2711–2715.
Protein kinase C delta is phosphorylated on five novel Ser/Thr sites following inducible overexpression in human colorectal cancer cells.CrossRef | 1:CAS:528:DC%2BD2sXhsVahsbrF&md5=287dc6ed2c5779278fc3936d5c78a2d6CAS | 17965192PubMed | open url image1

Winkel, G. K., Ferguson, J. E., Takeichi, M., and Nuccitelli, R. (1990). Activation of protein kinase C triggers premature compaction in the four-cell stage mouse embryo. Dev. Biol. 138, 1–15.
Activation of protein kinase C triggers premature compaction in the four-cell stage mouse embryo.CrossRef | 1:CAS:528:DyaK3cXhsFGkurg%3D&md5=b0e957d2a04855a4a2f5b37949714ae3CAS | 2407575PubMed | open url image1

Yang, Q. E., Fields, S. D., Zhang, K., Ozawa, M., Johnson, S. E., and Ealy, A. D. (2011a). Fibroblast growth factor 2 promotes primitive endoderm development in bovine blastocyst outgrowths. Biol. Reprod. 85, 946–953.
Fibroblast growth factor 2 promotes primitive endoderm development in bovine blastocyst outgrowths.CrossRef | 1:CAS:528:DC%2BC3MXhtl2is7bJ&md5=2bf0facfcedc5cee2228bd71d84ee674CAS | 21778141PubMed | open url image1

Yang, Q. E., Giassetti, M. I., and Ealy, A. D. (2011b). Fibroblast growth factors activate mitogen-activated protein kinase pathways to promote migration in ovine trophoblast cells. Reproduction 141, 707–714.
Fibroblast growth factors activate mitogen-activated protein kinase pathways to promote migration in ovine trophoblast cells.CrossRef | 1:CAS:528:DC%2BC3MXmvFCis7w%3D&md5=1778b8f44665388194520a1edb70ff67CAS | 21310815PubMed | open url image1

Yang, Q. E., Johnson, S. E., and Ealy, A. D. (2011c). Protein kinase C delta mediates fibroblast growth factor-2-induced interferon-tau expression in bovine trophoblast. Biol. Reprod. 84, 933–943.
Protein kinase C delta mediates fibroblast growth factor-2-induced interferon-tau expression in bovine trophoblast.CrossRef | 1:CAS:528:DC%2BC3MXltlGisro%3D&md5=b98b97921f91e57ce1cb47d73dca048cCAS | 21191110PubMed | open url image1

Zhang, K., Hansen, P. J., and Ealy, A. D. (2010). Fibroblast growth factor 10 enhances bovine oocyte maturation and developmental competence in vitro. Reproduction 140, 815–826.
Fibroblast growth factor 10 enhances bovine oocyte maturation and developmental competence in vitro.CrossRef | 1:CAS:528:DC%2BC3MXisFKqtLY%3D&md5=0827a13a11181330bbdce27d899312b8CAS | 20876224PubMed | open url image1



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