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

Immunological mechanisms to establish embryo tolerance in early bovine pregnancy

A. E. Groebner A , K. Schulke A , J. C. Schefold B , G. Fusch F , F. Sinowatz C , H. D. Reichenbach D , E. Wolf E , H. H. D. Meyer A and S. E. Ulbrich A G
+ Author Affiliations
- Author Affiliations

A Physiology Weihenstephan, ZIEL Research Center for Nutrition and Food Sciences, Technische Universitaet Muenchen, Weihenstephaner Berg 3, 85354 Freising, Germany.

B Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Department of Nephrology and Medical Intensive Care, Augustenburger Platz 1, 13353 Berlin, Germany.

C Institute of Veterinary Anatomy, Histology and Embryology, Ludwig-Maximilians Universitaet Muenchen, Veterinaerstr. 13, 80539 Muenchen, Germany.

D Institute of Animal Breeding, Bavarian State Institute for Agriculture, Prof.-Duerrwaechter-Platz 1, 85586 Grub, Germany.

E Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians Universitaet Muenchen, Feodor-Lynen-Str. 25, 81377 Muenchen, Germany.

F Department of Pediatrics, Ernst-Moritz Arndt University of Greifswald, Sauerbruchstrasse, 17489 Greifswald, Germany.

G Corresponding author. Email: ulbrich@wzw.tum.de

Reproduction, Fertility and Development 23(5) 619-632 https://doi.org/10.1071/RD10230
Submitted: 13 September 2010  Accepted: 21 December 2010   Published: 5 May 2011

Abstract

A well-balanced immunological interaction between mother and the semi-allogenic embryo is of particular importance. The objective of the present study was to analyse mechanisms of immune tolerance in bovine pregnancy during peri-implantation. Simmental heifers inseminated with either cryopreserved spermatozoa or seminal plasma were killed 12, 15 or 18 days after oestrus. Uteri were flushed for the recovery of conceptuses and the ipsilateral intercaruncular endometrium was sampled for gene expression analysis. Indoleamine 2,3-dioxygenase (IDO) mRNA, coding for the initial enzyme of the kynurenine pathway, was 18-fold (P < 0.001) more abundant in the endometrium of Day 18 pregnant v. non-pregnant animals. Tandem mass spectrometry revealed a decrease of endometrial l-tryptophan (P = 0.0008), but an increase of l-kynurenine concentration (P = 0.005) from Day 12 to Day 18, suggesting increasing IDO activity (P < 0.03). An in vitro coculture model of endometrial cells showed an induction of IDO expression following interferon-τ exposure primarily in stroma cells, which was confirmed by in situ hybridisation localising IDO mRNA mainly in deep stroma cells. Immunohistochemical analysis revealed fewer CD45-positive leucocytes in the zona basalis of pregnant animals. Elevated IDO activity may reduce the presence of leucocytes in the pregnant endometrium, providing a possible mechanism for protecting the semi-allogenic conceptus from maternal rejection.

Additional keywords: Bos taurus, endometrium, indoleamine 2,3-dioxygenase, peri-implantation.


References

Bauersachs, S., Ulbrich, S. E., Gross, K., Schmidt, S. E., Meyer, H. H., Einspanier, R., Wenigerkind, H., Vermehren, M., Blum, H., Sinowatz, F., and Wolf, E. (2005). Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes. J. Mol. Endocrinol. 34, 889–908.
Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXlslCisL8%3D&md5=d081dd2c742e60fd0ed43902b47546a2CAS | 15956356PubMed |

Bauersachs, S., Ulbrich, S. E., Gross, K., Schmidt, S. E., Meyer, H. H., Wenigerkind, H., Vermehren, M., Sinowatz, F., Blum, H., and Wolf, E. (2006). Embryo-induced transcriptome changes in bovine endometrium reveal species-specific and common molecular markers of uterine receptivity. Reproduction 132, 319–331.
Embryo-induced transcriptome changes in bovine endometrium reveal species-specific and common molecular markers of uterine receptivity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xpt1Wjs7s%3D&md5=33d6a11e661942e32cef6aa7017feac8CAS | 16885540PubMed |

Bazer, F. W., Burghardt, R. C., Johnson, G. A., Spencer, T. E., and Wu, G. (2008). Interferons and progesterone for establishment and maintenance of pregnancy: interactions among novel cell signaling pathways. Reprod. Biol. 8, 179–211.
| 19092983PubMed |

Bondurant, R. H. (1999). Inflammation in the bovine female reproductive tract. J. Anim. Sci. 77, 101–110.
| 1:CAS:528:DyaK1MXlvFWhtbc%3D&md5=9231a63888706072faaab7f0f687046aCAS | 15526785PubMed |

Choi, Y., Johnson, G. A., Burghardt, R. C., Berghman, L. R., Joyce, M. M., Taylor, K. M., Stewart, M. D., Bazer, F. W., and Spencer, T. E. (2001). Interferon regulatory factor-two restricts expression of interferon-stimulated genes to the endometrial stroma and glandular epithelium of the ovine uterus. Biol. Reprod. 65, 1038–1049.
Interferon regulatory factor-two restricts expression of interferon-stimulated genes to the endometrial stroma and glandular epithelium of the ovine uterus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnt1Cmsr0%3D&md5=f68a25a4ad63124308c6f80beb7676baCAS | 11566724PubMed |

Choi, Y., Johnson, G. A., Spencer, T. E., and Bazer, F. W. (2003). Pregnancy and interferon tau regulate major histocompatibility complex class I and beta2-microglobulin expression in the ovine uterus. Biol. Reprod. 68, 1703–1710.
Pregnancy and interferon tau regulate major histocompatibility complex class I and beta2-microglobulin expression in the ovine uterus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXjt12lt78%3D&md5=af91a0ba2fa01f9a72bcbad4f45ab0deCAS | 12606392PubMed |

Croy, B. A., van den Heuvel, M. J., Borzychowski, A. M., and Tayade, C. (2006). Uterine natural killer cells: a specialized differentiation regulated by ovarian hormones. Immunol. Rev. 214, 161–185.
Uterine natural killer cells: a specialized differentiation regulated by ovarian hormones.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtlClsr%2FE&md5=3b719449a6466aa6a2e68cbf56eb1d4dCAS | 17100884PubMed |

Dacal, V., Colwell, D. D., Lopez, C., Perez, V., Vazquez, L., Cienfuegos, S., Diaz, P., Morrondo, P., ez-Banos, P., and Panadero, R. (2009). Local and systemic cytokine responses during larval penetration in cattle experimentally infested with Hypoderma lineatum (Diptera: Oestridae). Vet. Immunol. Immunopathol. 131, 59–64.
Local and systemic cytokine responses during larval penetration in cattle experimentally infested with Hypoderma lineatum (Diptera: Oestridae).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtVSit7%2FN&md5=3ad9b43ea0fc76c401be61cb97e94134CAS | 19375172PubMed |

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=5080b295560059fd32eba476b0abf67dCAS | 10736242PubMed |

Davies, C. J., Eldridge, J. A., Fisher, P. J., and Schlafer, D. H. (2006). Evidence for expression of both classical and non-classical major histocompatibility complex class I genes in bovine trophoblast cells. Am. J. Reprod. Immunol. 55, 188–200.
Evidence for expression of both classical and non-classical major histocompatibility complex class I genes in bovine trophoblast cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjtlWlsLw%3D&md5=bc8090c15d74b39822505ca62350b38bCAS | 16451353PubMed |

Davies, D., Meade, K. G., Herath, S., Eckersall, P. D., Gonzalez, D., White, J. O., Conlan, R. S., O’Farrelly, C., and Sheldon, I. M. (2008). Toll-like receptor and antimicrobial peptide expression in the bovine endometrium. Reprod. Biol. Endocrinol. 6, 53.
Toll-like receptor and antimicrobial peptide expression in the bovine endometrium.Crossref | GoogleScholarGoogle Scholar | 19017375PubMed |

Della Chiesa, M., Carlomagno, S., Frumento, G., Balsamo, M., Cantoni, C., Conte, R., Moretta, L., Moretta, A., and Vitale, M. (2006). The tryptophan catabolite l-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function. Blood 108, 4118–4125.
The tryptophan catabolite l-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtlWqsrvF&md5=bd84696c9a66e87ace1f4c308be514ecCAS | 16902152PubMed |

Dore Jr., J. J., Wilkinson, J. E., and Godkin, J. D. (1996). Ovine endometrial expression of transforming growth factor beta isoforms during the peri-implantation period. Biol. Reprod. 54, 1080–1087.
Ovine endometrial expression of transforming growth factor beta isoforms during the peri-implantation period.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK28zgtFegsg%3D%3D&md5=96064c5ba81e0fe97fa482b249fbda5eCAS | 8722629PubMed |

Doyle, J., Ellis, S. A., O’Gorman, G. M., paricio Donoso, I. M., Lonergan, P., and Fair, T. (2009). Classical and non-classical major histocompatibility complex class I gene expression in in vitro derived bovine embryos. J. Reprod. Immunol. 82, 48–56.
Classical and non-classical major histocompatibility complex class I gene expression in in vitro derived bovine embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFGltbnL&md5=c582aa8a1e83bea7cfb2d07a25a6d6c7CAS | 19682752PubMed |

Drenzek, J. G., Breburda, E. E., Burleigh, D. W., Bondarenko, G. I., Grendell, R. L., and Golos, T. G. (2008). Expression of indoleamine 2,3-dioxygenase in the rhesus monkey and common marmoset. J. Reprod. Immunol. 78, 125–133.
Expression of indoleamine 2,3-dioxygenase in the rhesus monkey and common marmoset.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXnsF2ksLs%3D&md5=c500e2bce5eea7f715253a2ff83010baCAS | 18490060PubMed |

Fallarino, F., Grohmann, U., You, S., McGrath, B. C., Cavener, D. R., Vacca, C., Orabona, C., Bianchi, R., Belladonna, M. L., Volpi, C., Santamaria, P., Fioretti, M. C., and Puccetti, P. (2006). The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J. Immunol. 176, 6752–6761.
| 1:CAS:528:DC%2BD28XkslWhsbs%3D&md5=7fd2cefeb98bf6ac0d2b988c0e70dcc9CAS | 16709834PubMed |

Flynn, R. J., and Mulcahy, G. (2008). Possible role for Toll-like receptors in interaction of Fasciola hepatica excretory/secretory products with bovine macrophages. Infect. Immun. 76, 678–684.
Possible role for Toll-like receptors in interaction of Fasciola hepatica excretory/secretory products with bovine macrophages.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsFOqtro%3D&md5=9ed568a8a7b961ec9448adda00beb8a6CAS | 18070895PubMed |

Gao, H., Wu, G., Spencer, T. E., Johnson, G. A., and Bazer, F. W. (2009). Select nutrients in the ovine uterine lumen. IV. Expression of neutral and acidic amino acid transporters in ovine uteri and peri-implantation conceptuses. Biol. Reprod. 80, 1196–1208.
Select nutrients in the ovine uterine lumen. IV. Expression of neutral and acidic amino acid transporters in ovine uteri and peri-implantation conceptuses.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXmtlGmsLw%3D&md5=e2e58918bec5d5bb742fd4a9fca264fcCAS | 19176878PubMed |

Gogolin-Ewens, K. J., Lee, C. S., Mercer, W. R., and Brandon, M. R. (1989). Site-directed differences in the immune response to the fetus. Immunology 66, 312–317.
| 1:STN:280:DyaL1M7ntlSgtw%3D%3D&md5=c9e9fdf24858b804c1ecac9443287196CAS | 2925229PubMed |

Groebner, A. E., Schulke, K., Unterseer, S., Reichenbach, H. D., Reichenbach, M., Buttner, M., Wolf, E., Meyer, H. H., and Ulbrich, S. E. (2010). Enhanced proapoptotic gene expression of XAF1, CASP8 and TNFSF10 in the bovine endometrium during early pregnancy is not correlated with augmented apoptosis. Placenta 31, 168–177.
Enhanced proapoptotic gene expression of XAF1, CASP8 and TNFSF10 in the bovine endometrium during early pregnancy is not correlated with augmented apoptosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXit1Khsrw%3D&md5=50be85d9fd94f9afb290edc837e966e5CAS | 20092891PubMed |

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=747dde06dac121e9c3f8e20f859aad62CAS | 12079999PubMed |

Imakawa, K., Nagaoka, K., Nojima, H., Hara, Y., and Christenson, R. K. (2005). Changes in immune cell distribution and IL-10 production are regulated through endometrial IP-10 expression in the goat uterus. Am. J. Reprod. Immunol. 53, 54–64.
Changes in immune cell distribution and IL-10 production are regulated through endometrial IP-10 expression in the goat uterus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XpsF2rtw%3D%3D&md5=14f48fed84e1411b048f7394ae0945ceCAS | 15667526PubMed |

Jeddi-Tehrani, M., Abbasi, N., Dokouhaki, P., Ghasemi, J., Rezania, S., Ostadkarampour, M., Rabbani, H., Akhondi, M. A., Fard, Z. T., and Zarnani, A. H. (2009). Indoleamine 2,3-dioxygenase is expressed in the endometrium of cycling mice throughout the oestrous cycle. J. Reprod. Immunol. 80, 41–48.
Indoleamine 2,3-dioxygenase is expressed in the endometrium of cycling mice throughout the oestrous cycle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXms1Smsb0%3D&md5=56c79668a3ec9dbd948f4a30a137dedaCAS | 19410297PubMed |

Klein, C., Bauersachs, S., Ulbrich, S. E., Einspanier, R., Meyer, H. H., Schmidt, S. E., Reichenbach, H. D., Vermehren, M., Sinowatz, F., Blum, H., and Wolf, E. (2006). Monozygotic twin model reveals novel embryo-induced transcriptome changes of bovine endometrium in the preattachment period. Biol. Reprod. 74, 253–264.
Monozygotic twin model reveals novel embryo-induced transcriptome changes of bovine endometrium in the preattachment period.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xot1Kmuw%3D%3D&md5=f1206e3fbbe53a1cb000e5a03b4e81f9CAS | 16207835PubMed |

Lee, C. S., Meeusen, E., Gogolin-Ewens, K., and Brandon, M. R. (1992). Quantitative and qualitative changes in the intraepithelial lymphocyte population in the uterus of nonpregnant and pregnant sheep. Am. J. Reprod. Immunol. 28, 90–96.
| 1:STN:280:DyaK3s7lvFGksA%3D%3D&md5=10d8da00f60904c9fdd7ed15d04f6018CAS | 1285857PubMed |

Leung, S. T., Derecka, K., Mann, G. E., Flint, A. P., and Wathes, D. C. (2000). Uterine lymphocyte distribution and interleukin expression during early pregnancy in cows. J. Reprod. Fertil. 119, 25–33.
| 1:CAS:528:DC%2BD3cXjsF2ju74%3D&md5=934ae283da446c4d8f930e6000162ca4CAS | 10864810PubMed |

Lewis, G. S. (2003). Steroidal regulation of uterine resistance to bacterial infection in livestock. Reprod. Biol. Endocrinol. 1, 117.
Steroidal regulation of uterine resistance to bacterial infection in livestock.Crossref | GoogleScholarGoogle Scholar | 14641941PubMed |

Low, B. G., Hansen, P. J., Drost, M., and Gogolin-Ewens, K. J. (1990). Expression of major histocompatibility complex antigens on the bovine placenta. J. Reprod. Fertil. 90, 235–243.
Expression of major histocompatibility complex antigens on the bovine placenta.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3M%2FjvFSmtA%3D%3D&md5=9b87e038791c6995acd3db229587823dCAS | 2231545PubMed |

Meeusen, E., Fox, A., Brandon, M., and Lee, C. S. (1993). Activation of uterine intraepithelial gamma delta T cell receptor-positive lymphocytes during pregnancy. Eur. J. Immunol. 23, 1112–1117.
Activation of uterine intraepithelial gamma delta T cell receptor-positive lymphocytes during pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3s3jvVylug%3D%3D&md5=69ba0c24e06507f28c1c30d83ac7590cCAS | 8477805PubMed |

Meeusen, E. N., Bischof, R. J., and Lee, C. S. (2001). Comparative T-cell responses during pregnancy in large animals and humans. Am. J. Reprod. Immunol. 46, 169–179.
Comparative T-cell responses during pregnancy in large animals and humans.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3MvmtFWhtg%3D%3D&md5=d8b65fe3b0552d70163ef0729e36dca1CAS | 11506082PubMed |

Mellor, A. L., and Munn, D. H. (1999). Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol. Today 20, 469–473.
Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmsVWhsrg%3D&md5=e83ba8266f8386d55309810f19f9ac3cCAS | 10500295PubMed |

Mellor, A. L., and Munn, D. H. (2000). Immunology at the maternal–fetal interface: lessons for T cell tolerance and suppression. Annu. Rev. Immunol. 18, 367–391.
Immunology at the maternal–fetal interface: lessons for T cell tolerance and suppression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjs1Gmsbg%3D&md5=4cadb9d932acebdf101036e21d1b22f5CAS | 10837063PubMed |

Mellor, A. L., Sivakumar, J., Chandler, P., Smith, K., Molina, H., Mao, D., and Munn, D. H. (2001). Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat. Immunol. 2, 64–68.
Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjslylsw%3D%3D&md5=b6ea3a038efef199db9c4f53d6c8e801CAS | 11135580PubMed |

Padua, M. B., Tekin, S., Spencer, T. E., and Hansen, P. J. (2005). Actions of progesterone on uterine immunosuppression and endometrial gland development in the uterine gland knockout (UGKO) ewe. Mol. Reprod. Dev. 71, 347–357.
Actions of progesterone on uterine immunosuppression and endometrial gland development in the uterine gland knockout (UGKO) ewe.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXltFyhsrk%3D&md5=ce28caefacf5095985db4acab74950fcCAS | 15803459PubMed |

Prakash, B. S., Meyer, H. H., Schallenberger, E., and van de Wiel, D. F. (1987). Development of a sensitive enzymeimmunoassay (EIA) for progesterone determination in unextracted bovine plasma using the second antibody technique. J. Steroid Biochem. 28, 623–627.
Development of a sensitive enzymeimmunoassay (EIA) for progesterone determination in unextracted bovine plasma using the second antibody technique.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXkvFChtA%3D%3D&md5=028d0abd9eb3ee8a1c2e528ede89fcbeCAS | 3320573PubMed |

Puccetti, P., and Grohmann, U. (2007). IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-kappaB activation. Nat. Rev. Immunol. 7, 817–823.
IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-kappaB activation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVOrtbnN&md5=bd2a89390e0fc2d7b91cba51177ea425CAS | 17767193PubMed |

Roberts, R. M., Liu, L., Guo, Q., Leaman, D., and Bixby, J. (1998). The evolution of the type I interferons. J. Interferon Cytokine Res. 18, 805–816.
The evolution of the type I interferons.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXmvFCjt7c%3D&md5=2c1e1de8c73c072837fad819a562316dCAS | 9809615PubMed |

Roussev, R. G., and Coulam, C. B. (2007). HLA-G and its role in implantation. J. Assist. Reprod. Genet. 24, 288–295. [Review]10.1007/S10815-007-9148-3

Schallenberger, E., Schams, D., and Meyer, H. H. (1989). Sequences of pituitary, ovarian and uterine hormone secretion during the first 5 weeks of pregnancy in dairy cattle. J. Reprod. Fertil. Suppl. 37, 277–286.
| 1:CAS:528:DyaL1MXitVGqu78%3D&md5=10b599e635dd707a7ad0ef25130fded8CAS | 2509692PubMed |

Schefold, J. C., Zeden, J. P., Pschowski, R., Hammoud, B., Fotopoulou, C., Hasper, D., Fusch, G., VonHaehling, S., Volk, H. D., Meisel, C., Schutt, C., and Reinke, P. (2010). Treatment with granulocyte–macrophage colony-stimulating factor is associated with reduced indoleamine 2,3-dioxygenase activity and kynurenine pathway catabolites in patients with severe sepsis and septic shock. Scand. J. Infect. Dis. 42, 164–171.
Treatment with granulocyte–macrophage colony-stimulating factor is associated with reduced indoleamine 2,3-dioxygenase activity and kynurenine pathway catabolites in patients with severe sepsis and septic shock.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhs1Kmtbw%3D&md5=c8de068b441a89d47d538b4786b808f9CAS | 19958238PubMed |

Ulbrich, S. E., Frohlich, T., Schulke, K., Englberger, E., Waldschmitt, N., Arnold, G. J., Reichenbach, H. D., Reichenbach, M., Wolf, E., Meyer, H. H., and Bauersachs, S. (2009). Evidence for estrogen-dependent uterine serpin (SERPINA14) expression during estrus in the bovine endometrial glandular epithelium and lumen. Biol. Reprod. 81, 795–805.
Evidence for estrogen-dependent uterine serpin (SERPINA14) expression during estrus in the bovine endometrial glandular epithelium and lumen.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFyhsLbN&md5=1b9ebfd92d10b70bccb0032cfc543b5bCAS | 19494250PubMed |

Vander Wielen, A. L., and King, G. J. (1984). Intraepithelial lymphocytes in the bovine uterus during the oestrous cycle and early gestation. J. Reprod. Fertil. 70, 457–462.
Intraepithelial lymphocytes in the bovine uterus during the oestrous cycle and early gestation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2c7jvVertQ%3D%3D&md5=463bad6de9864baeca116178120cc52aCAS | 6699812PubMed |

von Rango, U. (2008). Fetal tolerance in human pregnancy: a crucial balance between acceptance and limitation of trophoblast invasion. Immunol. Lett. 115, 21–32.
Fetal tolerance in human pregnancy: a crucial balance between acceptance and limitation of trophoblast invasion.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtlejsg%3D%3D&md5=fd8e47b473546f034b7b83b3bd37f009CAS | 18055021PubMed |

von Rango, U., Krusche, C. A., Beier, H. M., and Classen-Linke, I. (2007). Indoleamine-dioxygenase is expressed in human decidua at the time maternal tolerance is established. J. Reprod. Immunol. 74, 34–45.
Indoleamine-dioxygenase is expressed in human decidua at the time maternal tolerance is established.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXkvFGgsbk%3D&md5=689a78a34d91f94964ac1df61115edb5CAS | 17321596PubMed |

Wolf, E., Arnold, G. J., Bauersachs, S., Beier, H. M., Blum, H., Einspanier, R., Frohlich, T., Herrler, A., Hiendleder, S., Kolle, S., Prelle, K., Reichenbach, H. D., Stojkovic, M., Wenigerkind, H., and Sinowatz, F. (2003). Embryo–maternal communication in bovine: strategies for deciphering a complex cross-talk. Reprod. Domest. Anim. 38, 276–289.
Embryo–maternal communication in bovine: strategies for deciphering a complex cross-talk.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3svis1Srtg%3D%3D&md5=ff84c6a9186741a541e73a7bba0935a9CAS | 12887567PubMed |

Wooding, F. B., and Wathes, D. C. (1980). Binucleate cell migration in the bovine placentome. J. Reprod. Fertil. 59, 425–430.
Binucleate cell migration in the bovine placentome.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL3M%2FkvFahtQ%3D%3D&md5=caaa4979f70571727905b9acc1d5d467CAS | 7431300PubMed |

Yoon, H. J., Jeon, S. B., Kim, I. H., and Park, E. J. (2008). Regulation of TLR2 expression by prostaglandins in brain glia. J. Immunol. 180, 8400–8409.
| 1:CAS:528:DC%2BD1cXntVeks78%3D&md5=a46a6796ff99abda06732ae27f2cb59aCAS | 18523308PubMed |

Zenclussen, A. C., Schumacher, A., Zenclussen, M. L., Wafula, P., and Volk, H. D. (2007). Immunology of pregnancy: cellular mechanisms allowing fetal survival within the maternal uterus. Expert Rev. Mol. Med. 9, 1–14.
Immunology of pregnancy: cellular mechanisms allowing fetal survival within the maternal uterus.Crossref | GoogleScholarGoogle Scholar |