Maternal plasma Interleukin-6 and early conception failure in dairy cows

Document Type : Research Paper

Authors

1 DVSc Student of Theriogenology, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran

2 Associate Professor, Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran

3 Professor, Department of Pathology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Assistant Professor Department of Applied Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran

Abstract

    Pro-inflammatory cytokines may contribute to physiological, e.g., tissue reconstruction and vascularization, or pathological, e.g., inflammation or some metabolic disturbances, processes during pregnancy establishment. The current study aimed to investigate IL-6 plasma levels at 30 and 45 days post-insemination (dpi) in pregnant and non-pregnant dairy cows. The cows were examined for pregnancy diagnosis at 30 and 45 dpi. Cows (n=71) were assigned into four groups: Non-pregnant at 30 dpi (n=16), pregnant at 30 dpi (n=36), non-pregnant at 45 dpi (n=11), and pregnant at 45 dpi (n=8). Blood samples were collected at 30 and 45 dpi for IL-6 assay. Results showed high levels of plasma IL-6 at 30 dpi either cow-conceived or not. Cows with healthy embryos at 45 dpi had lower concentrations of IL-6 than cows with late embryonic death. The plasma IL-6 concentrations showed different patterns of changes in dairy cows during the first two months of pregnancy.

Keywords

Main Subjects


Abrahams, V. M., Aldo, P. B., Murphy, S. P., Visintin, I., Koga, K., Wilson, G., Romero, R., Sharma, S., & Mor, G. (2008). TLR6 modulates first trimester trophoblast responses to peptidoglycan [Article]. Journal of Immunology, 180(9), 6035-6043. https://doi.org/10.4049/jimmunol.180.9.6035
Agarwal, R., Loganath, A., Roy, A. C., Wong, Y. C., Lindoff, C., & Ng, S. C. (2000). Increased expression of interleukin 6 in term compared to the first trimester human placental villi [Article]. Hormone and Metabolic Research, 32(5), 164-168. https://doi.org/10.1055/s-2007-978615
Agarwal, R., Loganath, A., Roy, A. C., Wong, Y. C., & Ng, S. C. (2000). Effect of T-helper 1 cytokines on secretion of T-helper 2 cytokines by term trophoblast cells in culture [Article]. Gynecological Endocrinology, 14(5), 305-310. https://doi.org/10.3109/09513590009167697
Almeria, S., Araujo, R. N., Darwich, L., Dubey, J. P., & Gasbarre, L. C. (2011). Cytokine gene expression at the materno-foetal interface after experimental Neospora caninum infection of heifers at 110 days of gestation [Article]. Parasite Immunology, 33(9), 517-523. https://doi.org/10.1111/j.1365-3024.2011.01307.x
Aris, A., Lambert, F., Bessette, P., & Moutquin, J. M. (2008). Maternal circulating interferon‐γ and interleukin‐6 as biomarkers of Th1/Th2 immune status throughout pregnancy. Journal of Obstetrics and Gynaecology Research, 34(1), 7-11.
Atluru, D., Xue, W., Polam, S., Atluru, S., Blecha, F., & Minocha, H. C. (1990). In vitro interactions of cytokines and bovine viral diarrhea virus in phytohemagglutinin-stimulated bovine mononuclear cells. Veterinary Immunol Immunopathol, 25(1), 47-59. https://doi.org/10.1016/0165-2427(90)90109-6
Balakrishnan, A., Guruprasad, K. P., Satyamoorthy, K., & Joshi, M. B. (2018). Interleukin-6 determines protein stabilization of DNA methyltransferases and alters DNA promoter methylation of genes associated with insulin signaling and angiogenesis [Article]. Laboratory Investigation, 98(9), 1143-1158. https://doi.org/10.1038/s41374-018-0079-7
Bednarska-Czerwińska, A., Mercik, D., & Czerwiński, M. (2015). Endometrial receptivity forming elements [Review]. Ginekologia i Poloznictwo, 38(4), 15-19. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84954236570&partnerID=40&md5=f2a4c4cfd4e9fb7b9208146af8894fc0
Beltman, M. E., Forde, N., Lonergan, P., & Crowe, M. A. (2013). Altered endometrial immune gene expression in beef heifers with retarded embryos [Article]. Reproduction, Fertility and Development, 25(6), 966-970. https://doi.org/10.1071/RD12232
Bennett, W. A., Lagoo-Deenadayalan, S., Whitworth, N. S., Stopple, J. A., Barber, W. H., Hale, E., Brackin, M. N., & Cowan, B. D. (1999). First-trimester human chorionic villi express both immunoregulatory and inflammatory cytokines: A role for interleukin-10 in regulating the cytokine network of pregnancy [Conference Paper]. American Journal of Reproductive Immunology, 41(1), 70-78. https://doi.org/10.1111/j.1600-0897.1999.tb00077.x
Blitek, A., Morawska, E., & Ziecik, A. J. (2012). Regulation of expression and role of leukemia inhibitory factor and interleukin-6 in the uterus of early pregnant pigs [Article]. Theriogenology, 78(5), 951-964. https://doi.org/10.1016/j.theriogenology.2012.05.016
Campos, C. C., Hartling, I., Kaur, M., Fernandes, A. C. C., Santos, R. M., & Cerri, R. L. A. (2018). Intramammary infusion of lipopolysaccharide promotes inflammation and alters endometrial gene expression in lactating Holstein cows [Article]. Journal of Dairy Science, 101(11), 10440-10455. https://doi.org/10.3168/jds.2018-14393
Chang, S. C., & Vivian Yang, W. C. (2013). Hyperglycemia induces altered expressions of angiogenesis associated molecules in the trophoblast [Article]. Evidence-based Complementary and Alternative Medicine, 2013, Article 457971. https://doi.org/10.1155/2013/457971
Chen, Q., Chen, L., Liu, B., Vialli, C., Stone, P., Ching, L. M., & Chamley, L. (2010). The role of autocrine TGFβ1 in endothelial cell activation induced by phagocytosis of necrotic trophoblasts: A possible role in the pathogenesis of pre-eclampsia [Article]. Journal of Pathology, 221(1), 87-95. https://doi.org/10.1002/path.2690
Cui, L., Cai, H., Sun, F., Wang, Y., Qu, Y., Dong, J., Wang, H., Li, J., Qian, C., & Li, J. (2021). Beta-endorphin inhibits the inflammatory response of bovine endometrial cells through δ opioid receptor in vitro [Article]. Developmental and Comparative Immunology, 121, Article 104074. https://doi.org/10.1016/j.dci.2021.104074
Cui, L., Shao, X., Sun, W., Zheng, F., Dong, J., Li, J., Wang, H., & Li, J. (2022). Anti-inflammatory effects of progesterone through NF-κB and MAPK pathway in lipopolysaccharide- or Escherichia colistimulated bovine endometrial stromal cells [Article]. PLoS ONE, 17(4 April), Article e0266144. https://doi.org/10.1371/journal.pone.0266144
Cui, L., Wang, Y., Wang, H., Dong, J., Li, Z., Li, J., Qian, C., & Li, J. (2020). Different effects of cortisol on pro-inflammatory gene expressions in LPS-, heat-killed E.coli-, or live E.coli-stimulated bovine endometrial epithelial cells [Article]. BMC Veterinary Research, 16(1), Article 9. https://doi.org/10.1186/s12917-020-2231-z
Ding, J., Yang, C., Cheng, Y., Wang, J., Zhang, S., Yan, S., He, F., Yin, T., & Yang, J. (2021). Trophoblast-derived IL-6 serves as an important factor for normal pregnancy by activating Stat3-mediated M2 macrophages polarization [Article]. International Immunopharmacology, 90, Article 106788. https://doi.org/10.1016/j.intimp.2020.106788
Fagundes, N. S., Rezende, A. L., Alvarenga, P. B., Magalhães, L. Q., Santos, R. M., Headley, S. A., Silva, M. J. B., Beletti, M. E., & Saut, J. P. E. (2019). Short communication: Proinflammatory gene expression relative to the collection technique of endometrial samples from cows with and without subclinical endometritis [Article]. Journal of Dairy Science, 102(6), 5511-5517. https://doi.org/10.3168/jds.2018-15212
Goryszewska, E., Kaczynski, P., Baryla, M., & Waclawik, A. (2021). Pleiotropic role of prokineticin 1 in the porcine endometrium during pregnancy establishment and embryo implantation [Article]. Biology of Reproduction, 104(1), 181-196. https://doi.org/10.1093/biolre/ioaa181
Jauniaux, E., Gulbis, B., Schandene, L., Collette, J., & Hustin, J. (1996). Distribution of interleukin-6 in maternal and embryonic tissues during the first trimester [Article]. Molecular Human Reproduction, 2(4), 239-243. https://doi.org/10.1093/molehr/2.4.239
Markert, U. R., Morales-Prieto, D. M., & Fitzgerald, J. S. (2011). Understanding the link between the IL-6 cytokine family and pregnancy: Implications for future therapeutics [Review]. Expert Review of Clinical Immunology, 7(5), 603-609. https://doi.org/10.1586/eci.11.60
Neki, R., Matsuzaki, N., Yamanaka, K., Shimoya, K., Okada, T., Saji, F., Iwashita, M., & Tanizawa, O. (1993). The interleukin-6 (IL-6)/IL-6-receptor system induces human chorionic gonadotropin production by activating tyrosine kinase-dependent signal transduction pathway different from pathways triggered by protein kinase activators including gonadotropin releasing hormone [Article]. Journal of Clinical Endocrinology and Metabolism, 77(3), 704-709. https://doi.org/10.1210/jcem.77.3.8370693
Prins, J. R., Gomez-Lopez, N., & Robertson, S. A. (2012). Interleukin-6 in pregnancy and gestational disorders [Review]. Journal of Reproductive Immunology, 95(1-2), 1-14. https://doi.org/10.1016/j.jri.2012.05.004
Sakurai, T., Takai, R., Bürgin, H., Ishihara, K., Sakamoto, Y., Amano, J., Higuchi, Y., Chiba, S., Singer, T., Kawamura, A., Suzuki, M., & Müller, L. (2012). The Effects of Interleukin-6 Signal Blockade on Fertility, Embryo-fetal Development, and Immunization In vivo [Article]. Birth Defects Research Part B - Developmental and Reproductive Toxicology, 95(4), 304-317. https://doi.org/10.1002/bdrb.21019
Seekford, Z. K., Wooldridge, L. K., Dias, N. W., Timlin, C. L., Sales, Á. F., Speckhart, S. L., Pohler, K. G., Cockrum, R. R., Mercadante, V. R. G., & Ealy, A. D. (2021). Interleukin-6 supplementation improves post-transfer embryonic and fetal development of in vitro-produced bovine embryos [Article]. Theriogenology, 170, 15-22. https://doi.org/10.1016/j.theriogenology.2021.04.004
Singh, M., Kindelberger, D., Nagymanyoki, Z., Ng, S. W., Quick, C. M., Yamamoto, H., Fichorova, R., Fulop, V., & Berkowitz, R. S. (2012). Vascular endothelial growth factors and their receptors and regulators in gestational trophoblastic diseases and normal placenta [Article]. Journal of Reproductive Medicine, 57(5-6), 197-203. https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864106738&partnerID=40&md5=99fb793dd5a951ae909184da7fe233b7
Smith, S. E., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007). Maternal immune activation alters fetal brain development through interleukin-6. Journal of Neuroscience, 27(40), 10695-10702.
Srinivasan, L., Harris, M. C., & Kilpatrick, L. E. (2017). Cytokines and inflammatory response in the fetus and neonate. Fetal and Neonatal Physiology, 1241, e4-1254.