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

Gene expression and lymphocyte population at the fetal-maternal interface in sheep pregnancies established by somatic cell nuclear transfer

Jason A. Koroghli A B , Elizabeth Floyd A , Misha Regouski A , Kerry Rood A B , Kirsten Gash A , Kip Panter C , Rusty Stott A B , Christopher J. Davies A B , Irina A. Polejaeva A and Heloisa M. Rutigliano A B D
+ Author Affiliations
- Author Affiliations

A Department of Animal, Dairy and Veterinary Sciences, Utah State University, 4815 Old Main Hill, Logan, UT 84322, USA.

B School of Veterinary Medicine, Utah State University, 4815 Old Main Hill, Logan, UT 84322, USA.

C USDA ARS Poisonous Plant Research Laboratory, Logan, UT 84341, USA.

D Corresponding author. Email: heloisa.rutigliano@usu.edu

Reproduction, Fertility and Development 30(7) 1011-1020 https://doi.org/10.1071/RD17224
Submitted: 4 October 2016  Accepted: 19 November 2017   Published: 15 January 2018

Abstract

The hypothesis of this study was that the leukocyte populations and expression levels of genes related to immune response, growth factors and apoptosis would be altered at the fetal-maternal interface in somatic cell nuclear transfer (SCNT)-generated sheep pregnancies. Placental and endometrial samples from sheep pregnancies established by SCNT and natural breeding (control) were collected at 45 days and at term. Expression of genes related to growth factors, apoptosis and immune response was examined using quantitative reverse transcription polymerase chain reaction. Endometrial leukocyte populations and major histocompatibility class I (MHC-I) protein expression were examined by immunohistochemistry. At term we observed altered expression of genes related to apoptosis, growth factors and immune response in placental and endometrial tissue of SCNT pregnancies. In Day-45 pregnancies there was less-pronounced abnormal expression and only genes related to apoptosis and growth factors were abnormal in the placenta. Endometrial gene expression profiles were similar to age-matched controls. Placental MHC-I protein expression was similar in SCNT and controls at 45 days but increased in the SCNT at term. The altered gene expression at the fetal-maternal interface likely contributes to the placental dysfunction and overgrowth observed in sheep SCNT pregnancies.

Additional keywords: assisted reproductive technologies, cloning, large offspring syndrome, livestock species, pregnancy loss.


References

Arck, P. C., Ferrick, D. A., Steele-Norwood, D., Egan, P. J., Croitoru, K., Carding, S. R., Dietl, J., and Clark, D. A. (1999). Murine T cell determination of pregnancy outcome. Cell. Immunol. 196, 71–79.
Murine T cell determination of pregnancy outcome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXms1yhu7c%3D&md5=e0df165c1e488a77e8f13d4b43fa2d73CAS |

Benedictus, L., Thomas, A. J., Jorritsma, R., Davies, C. J., and Koets, A. P. (2012). Two-way calf to dam major histocompatibility class I compatibility increases risk for retained placenta in cattle. Am. J. Reprod. Immunol. 67, 224–230.
Two-way calf to dam major histocompatibility class I compatibility increases risk for retained placenta in cattle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xktlensr8%3D&md5=7024e86ced65c0cc76a4d0dce08c405fCAS |

Campbell, K. H., McWhir, J., Ritchie, W. A., and Wilmut, I. (1996). Sheep cloned by nuclear transfer from a cultured cell line. Nature 380, 64–66.
Sheep cloned by nuclear transfer from a cultured cell line.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XhsFeisLY%3D&md5=9942394765f399ca85b74c01c32c7336CAS |

Chaouat, G., Menu, E., Clark, D. A., Dy, M., Minkowski, M., and Wegmann, T. G. (1990). Control of fetal survival in CBA × DBA/2 mice by lymphokine therapy. J. Reprod. Fertil. 89, 447–458.
Control of fetal survival in CBA × DBA/2 mice by lymphokine therapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXlsFSnsb0%3D&md5=ab2e51185e2edbf4cfcb392cbaebf8a3CAS |

Chaouat, G., Assal Meliani, A., Martal, J., Raghupathy, R., Elliott, J. F., Elliot, J., Mosmann, T., and Wegmann, T. G. (1995). IL-10 prevents naturally occurring fetal loss in the CBA × DBA/2 mating combination, and local defect in IL-10 production in this abortion-prone combination is corrected by in vivo injection of IFN-tau. J. Immunol. 154, 4261–4268.
| 1:CAS:528:DyaK2MXltF2gt7o%3D&md5=65abc35c88b31c847fa5f1951f32dc62CAS |

Chavatte-Palmer, P., Heyman, Y., Richard, C., Monget, P., LeBourhis, D., Kann, G., Chilliard, Y., Vignon, X., and Renard, J. P. (2002). Clinical, hormonal, and hematologic characteristics of bovine calves derived from nuclei from somatic cells. Biol. Reprod. 66, 1596–1603.
Clinical, hormonal, and hematologic characteristics of bovine calves derived from nuclei from somatic cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XjvFegtb4%3D&md5=a817d1f8ad480ca7c7cd137a5df98d43CAS |

Chavatte-Palmer, P., Camous, S., Jammes, H., Le Cleac’h, N., Guillomot, M., and Lee, R. S. F. (2012). Review: placental perturbations induce the developmental abnormalities often observed in bovine somatic cell nuclear transfer. Placenta 33, S99–S104.
Review: placental perturbations induce the developmental abnormalities often observed in bovine somatic cell nuclear transfer.Crossref | GoogleScholarGoogle Scholar |

Constant, F., Guillomot, M., Heyman, Y., Vignon, X., Laigre, P., Servely, J. L., Renard, J. P., and Chavatte-Palmer, P. (2006). Large offspring or large placenta syndrome? Morphometric analysis of late gestation bovine placentomes from somatic nuclear transfer pregnancies complicated by hydrallantois. Biol. Reprod. 75, 122–130.
Large offspring or large placenta syndrome? Morphometric analysis of late gestation bovine placentomes from somatic nuclear transfer pregnancies complicated by hydrallantois.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xmtlyisbs%3D&md5=001f76e43fcb4328e4e84dc29fea1fcdCAS |

Davies, C. J., Fisher, P. J., and Schlafer, D. H. (2000). Temporal and regional regulation of major histocompatibility complex class I expression at the bovine uterine–placental interface. Placenta 21, 194–202.
Temporal and regional regulation of major histocompatibility complex class I expression at the bovine uterine–placental interface.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjtVamtrw%3D&md5=1f5bc81ef3be79cdc283fca1e6e9e8deCAS |

Davies, C. J., Hill, J. R., Edwards, J. L., Schrick, F. N., Fisher, P. J., Eldridge, J. A., and Schlafer, D. H. (2004). Major histocompatibility antigen expression on the bovine placenta: its relationship to abnormal pregnancies and retained placenta. Anim. Reprod. Sci. 82–83, 267–280.
Major histocompatibility antigen expression on the bovine placenta: its relationship to abnormal pregnancies and retained placenta.Crossref | GoogleScholarGoogle Scholar |

Edwards, J. L., Schrick, F. N., McCracken, M. D., van Amstel, S. R., Hopkins, F. M., Welborn, M. G., and Davies, C. J. (2003). Cloning adult farm animals: a review of the possibilities and problems associated with somatic cell nuclear transfer. Am. J. Reprod. Immunol. 50, 113–123.
Cloning adult farm animals: a review of the possibilities and problems associated with somatic cell nuclear transfer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3szhslaltA%3D%3D&md5=402aa90155f693288761ac3f4e75e982CAS |

Erlebacher, A. (2013). Immunology of the maternal–fetal interface. Annu. Rev. Immunol. 31, 387–411.
Immunology of the maternal–fetal interface.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXnsFClsb8%3D&md5=67ba403c1ec88b3b0f8f992bc04b50b2CAS |

Hashizume, K., Ishiwata, H., Kizaki, K., Yamada, O., Takahashi, T., Imai, K., Patel, O. V., Akagi, S., Shimizu, M., Takahashi, S., Katsuma, S., Shiojima, S., Hirasawa, A., Tsujimoto, G., Todoroki, J., and Izaike, Y. (2002). Implantation and placental development in somatic cell clone recipient cows. Cloning Stem Cells 4, 197–209.
Implantation and placental development in somatic cell clone recipient cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XnvFSksrg%3D&md5=1eb728102f5bc131444ea337bc1977daCAS |

Hill, J. R., Roussel, A. J., Cibelli, J. B., Edwards, J. F., Hooper, N. L., Miller, M. W., Thompson, J. A., Looney, C. R., Westhusin, M. E., Robl, J. M., and Stice, S. L. (1999). Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies). Theriogenology 51, 1451–1465.
Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies).Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c7ptFCitQ%3D%3D&md5=1b33a79505f0d0408e1fb5d0bad2a048CAS |

Hill, J. R., Burghardt, R. C., Jones, K., Long, C. R., Looney, C. R., Shin, T., Spencer, T. E., Thompson, J. A., Winger, Q. A., and Westhusin, M. E. (2000). Evidence for placental abnormality as the major cause of mortality in first-trimester somatic cell cloned bovine fetuses. Biol. Reprod. 63, 1787–1794.
Evidence for placental abnormality as the major cause of mortality in first-trimester somatic cell cloned bovine fetuses.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXosVKhtL4%3D&md5=12e422b8ac8cacb6f0da88e25ff527feCAS |

Hill, J. R., Schlafer, D. H., Fisher, P. J., and Davies, C. J. (2002). Abnormal expression of trophoblast major histocompatibility complex class I antigens in cloned bovine pregnancies is associated with a pronounced endometrial lymphocytic response. Biol. Reprod. 67, 55–63.
Abnormal expression of trophoblast major histocompatibility complex class I antigens in cloned bovine pregnancies is associated with a pronounced endometrial lymphocytic response.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XkvV2itrc%3D&md5=da7e75ff4f05cfc09f23e60f9c2a331eCAS |

Jenkins, C., Roberts, J., Wilson, R., MacLean, M. A., Shilito, J., and Walker, J. J. (2000). Evidence of a T(H) 1 type response associated with recurrent miscarriage. Fertil. Steril. 73, 1206–1208.
Evidence of a T(H) 1 type response associated with recurrent miscarriage.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3czhsF2gug%3D%3D&md5=2697eef72d502575d5bfa4ee15112fe9CAS |

Ko, Y.-G., Hwang, S., Kim, S., Kim, H., Seong, H., Kim, J.-H., Song, Y., Yang, B.-S., Song, Y., and Cho, J.-H. (2014). Proteomic analysis of the extraembryonic tissues from cloned porcine fetus at Day 35 of pregnancy. BMC Res. Notes 7, 861.
Proteomic analysis of the extraembryonic tissues from cloned porcine fetus at Day 35 of pregnancy.Crossref | GoogleScholarGoogle Scholar |

Lawn, A. M., Chiquoine, A. D., and Amoroso, E. C. (1969). The development of the placenta in the sheep and goat: an electron microscope study. J. Anat. 105, 557–578.
| 1:STN:280:DyaE3c%2FjtFymsA%3D%3D&md5=1a29cde5902df7cfcab00a876a0adbc9CAS |

Li, X., Amarnath, D., Kato, Y., and Tsunoda, Y. (2006). Analysis of development-related gene expression in cloned bovine blastocysts with different developmental potential. Cloning Stem Cells 8, 41–50.
Analysis of development-related gene expression in cloned bovine blastocysts with different developmental potential.Crossref | GoogleScholarGoogle Scholar |

Lim, K. J., Odukoya, O. A., Ajjan, R. A., Li, T. C., Weetman, A. P., and Cooke, I. D. (2000). The role of T-helper cytokines in human reproduction. Fertil. Steril. 73, 136–142.
The role of T-helper cytokines in human reproduction.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c%2Fps1aruw%3D%3D&md5=9e5967573bb1a3184f225fb60a40bb6fCAS |

Lin, H., Mosmann, T. R., Guilbert, L., Tuntipopipat, S., and Wegmann, T. G. (1993). Synthesis of T helper 2-type cytokines at the maternal–fetal interface. J. Immunol. 151, 4562–4573.
| 1:CAS:528:DyaK2cXmsFKj&md5=79c853c9cf58fc4dfcf4872b4a98de21CAS |

Livak, K. J., and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25, 402–408.
Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhtFelt7s%3D&md5=a80b5e0841c49e736a3564bfe77a7aa6CAS |

Loi, P., Clinton, M., Vackova, I., Fulka, J., Feil, R., Palmieri, C., Della Salda, L., and Ptak, G. (2006). Placental abnormalities associated with post-natal mortality in sheep somatic cell clones. Theriogenology 65, 1110–1121.
Placental abnormalities associated with post-natal mortality in sheep somatic cell clones.Crossref | GoogleScholarGoogle Scholar |

Mansouri-Attia, N., Oliveira, L. J., Forde, N., Fahey, A. G., Browne, J. A., Roche, J. F., Sandra, O., Reinaud, P., Lonergan, P., and Fair, T. (2012). Pivotal role for monocytes/macrophages and dendritic cells in maternal immune response to the developing embryo in cattle. Biol. Reprod. 87, 123.
Pivotal role for monocytes/macrophages and dendritic cells in maternal immune response to the developing embryo in cattle.Crossref | GoogleScholarGoogle Scholar |

Medawar, P. B. (1953). Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp. Soc. Exp. Biol. 7, 320–338.

Moffett, A., Chazara, O., and Colucci, F. (2017). Maternal allo-recognition of the fetus. Fertil. Steril. 107, 1269–1272.
Maternal allo-recognition of the fetus.Crossref | GoogleScholarGoogle Scholar |

Moore, K., Kramer, J. M., Rodriguez-Sallaberry, C. J., Yelich, J. V., and Drost, M. (2007). Insulin-like growth factor (IGF) family genes are aberrantly expressed in bovine conceptuses produced in vitro or by nuclear transfer. Theriogenology 68, 717–727.
Insulin-like growth factor (IGF) family genes are aberrantly expressed in bovine conceptuses produced in vitro or by nuclear transfer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXos1Sgsrk%3D&md5=7eb81c17a9a2e21ba9f2fafe3f6d1a19CAS |

Oliveira, L. J., Barreto, R. S. N., Perecin, F., Mansouri-Attia, N., Pereira, F. T. V., and Meirelles, F. V. (2012). Modulation of maternal immune system during pregnancy in the cow. Reprod. Domest. Anim. 47, 384–393.
Modulation of maternal immune system during pregnancy in the cow.Crossref | GoogleScholarGoogle Scholar |

Oliveira, L. J., Mansourri-Attia, N., Fahey, A. G., Browne, J., Forde, N., Roche, J. F., Lonergan, P., and Fair, T. (2013). Characterization of the Th profile of the bovine endometrium during the oestrous cycle and early pregnancy. PLoS One 8, e75571.
Characterization of the Th profile of the bovine endometrium during the oestrous cycle and early pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhslWks7rE&md5=b9f80cd537b156cf1ba7d13347d27082CAS |

Piccinni, M. P., Beloni, L., Livi, C., Maggi, E., Scarselli, G., and Romagnani, S. (1998). Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions. Nat. Med. 4, 1020–1024.
Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXlvFGjtbc%3D&md5=c4e67aa498fd99e0f81dc02eb34440a9CAS |

Piccinni, M. P., Scaletti, C., Maggi, E., and Romagnani, S. (2000). Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy. J. Neuroimmunol. 109, 30–33.
Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXmtVCku70%3D&md5=d946fc25d260b48f16bade6100e6c102CAS |

Reggio, B. C., James, A. N., Green, H. L., Gavin, W. G., Behboodi, E., Echelard, Y., and Godke, R. A. (2001). Cloned transgenic offspring resulting from somatic cell nuclear transfer in the goat: oocytes derived from both follicle-stimulating hormone-stimulated and nonstimulated abattoir-derived ovaries. Biol. Reprod. 65, 1528–1533.
Cloned transgenic offspring resulting from somatic cell nuclear transfer in the goat: oocytes derived from both follicle-stimulating hormone-stimulated and nonstimulated abattoir-derived ovaries.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnvVersLw%3D&md5=22497aa9de934825d324f0506b9b7837CAS |

Rutigliano, H. M., Thomas, A. J., Wilhelm, A., Sessions, B. R., Hicks, B. A., Schlafer, D. H., White, K. L., and Davies, C. J. (2016). Trophoblast major histocompatibility complex class I expression is associated with immune-mediated rejection of bovine fetuses produced by cloning. Biol. Reprod. 95, 39.
Trophoblast major histocompatibility complex class I expression is associated with immune-mediated rejection of bovine fetuses produced by cloning.Crossref | GoogleScholarGoogle Scholar |

Rutigliano, H. M., Wilhelm, A., Hall, J., Shi, B., Meng, Q., Stott, R., Bunch, T. D., White, K. L., Davies, C. J., and Polejaeva, I. A. (2017). Cytokine gene expression at the maternal–fetal interface after somatic cell nuclear transfer pregnancies in small ruminants. Reprod. Fertil. Dev. 29, 646–657.
Cytokine gene expression at the maternal–fetal interface after somatic cell nuclear transfer pregnancies in small ruminants.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXksVegsrk%3D&md5=07b4592ade11889227352234485b8688CAS |

Saito, S., Umekage, H., Sakamoto, Y., Sakai, M., Tanebe, K., Sasaki, Y., and Morikawa, H. (1999). Increased T-helper-1-type immunity and decreased T-helper-2-type immunity in patients with pre-eclampsia. Am. J. Reprod. Immunol. 41, 297–306.
Increased T-helper-1-type immunity and decreased T-helper-2-type immunity in patients with pre-eclampsia.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1MzgsFOrtQ%3D%3D&md5=3dbe6daa4bec8c3a4f715f9c2463d39aCAS |

Sargent, I. L., Borzychowski, A. M., and Redman, C. W. G. (2006). NK cells and human pregnancy – an inflammatory view. Trends Immunol. 27, 399–404.
NK cells and human pregnancy – an inflammatory view.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XotlKhtrg%3D&md5=be108c7eeedc38e8d69e08ee900af31cCAS |

Schnieke, A. E., Kind, A. J., Ritchie, W. A., Mycock, K., Scott, A. R., Ritchie, M., Wilmut, I., Colman, A., and Campbell, K. H. (1997). Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278, 2130–2133.
Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXhvFyh&md5=c128eda678bbb33e5eecbaa141458f75CAS |

Spurgeon, S. L., Jones, R. C., and Ramakrishnan, R. (2008). High throughput gene expression measurement with real time PCR in a microfluidic dynamic array. PloS One 3, e1662.
High throughput gene expression measurement with real time PCR in a microfluidic dynamic array.Crossref | GoogleScholarGoogle Scholar |

Tsuda, H., Michimata, T., Sakai, M., Nagata, K., Nakamura, M., and Saito, S. (2001). A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy. Clin. Exp. Immunol. 123, 105–111.
A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXhtF2mtrw%3D&md5=40e397cf3a7d6fc924b4c07fbe7da07fCAS |

Wegmann, T. G., Lin, H., Guilbert, L., and Mosmann, T. R. (1993). Bidirectional cytokine interactions in the maternal–fetal relationship: is successful pregnancy a Th2 phenomenon? Immunol. Today 14, 353–356.
Bidirectional cytokine interactions in the maternal–fetal relationship: is successful pregnancy a Th2 phenomenon?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXlsFOksL0%3D&md5=77d2f7b7628764d31529d03fdaf451b5CAS |

Wells, D. N., Misica, P. M., Day, T. A., and Tervit, H. R. (1997). Production of cloned lambs from an established embryonic cell line: a comparison between in vivo- and in vitro-matured cytoplasts. Biol. Reprod. 57, 385–393.
Production of cloned lambs from an established embryonic cell line: a comparison between in vivo- and in vitro-matured cytoplasts.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXkslWgtLg%3D&md5=83efbbd3701340c7d83d7b7d68e5cbc4CAS |

Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J., and Campbell, K. H. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810–813.
Viable offspring derived from fetal and adult mammalian cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXhsFamsLs%3D&md5=4680d0f6dc1331b02c8c2c52a16a6465CAS |

Yang, M., Hall, J., Fan, Z., Regouski, M., Meng, Q., Rutigliano, H. M., Stott, R., Rood, K. A., Panter, K. E., and Polejaeva, I. A. (2016). Oocytes from small and large follicles exhibit similar development competence following goat cloning despite their differences in meiotic and cytoplasmic maturation. Theriogenology 86, 2302–2311.
Oocytes from small and large follicles exhibit similar development competence following goat cloning despite their differences in meiotic and cytoplasmic maturation.Crossref | GoogleScholarGoogle Scholar |