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. 2019 Sep 30;15(4):443–452. doi: 10.1007/s13273-019-0048-2

In vitro estimation of metal-induced disturbance in chicken gut-oviduct chemokine circuit

Ki Hyung Kim 1,2,3,#, Juil Kim 1,#, Jae Yong Han 4, Yuseok Moon 1,2,5,✉
PMCID: PMC7097086  PMID: 32226460

Abstract

Backgrounds

Heavy metals affect various processes in the embryonic development. Embryonic fibroblasts (EFs) play key roles in the innate recognition and wound healing in reproductive tissues.

Methods

Based on the relative toxicities of different inorganic metals and inorganic nonmetallic compounds against murine and chicken EF cells, mechanistic estimations were performed based on transcriptomic analyses.

Results

Lead (II) acetate induced preferential injuries in the chicken EF and mechanistic analyses using transcriptome revealed that chemokine receptor-associated events are potently involved in metal-induced adverse actions. As an early sentinel of metal exposure, the precision-cut intestine slices (PCIS) induced the expression of chemokines including CXCLi1 or CXCLi2, which were potent gut-derived factors that activate chemokine receptors in reproductive organs after circulation.

Conclusion

EF-selective metals can be estimated to trigger the chemokine circuit in the gut-reproductive axis of chickens. This in vitro methodology using PCIS-EF culture could be used as a promising alternate platform for the reproductive immunotoxicological assessment.

Keywords: Heavy metals, Embryonic fibroblasts, PCIS, Chemokine receptor

Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2016R1D1A3B03931577).

Footnotes

Conflict of Interest

Ki Hyung Kim, Juil Kim, Jae Yong Han and Yuseok Moon declare that they have no conflicts of interest associated with the contents of this article.

Human and animal rights

The article does not contain any studies with human. Animal experimental protocols performed in this study were reviewed and approved by the Animal Ethics Committee of Pusan National University (PNU)-IACUC (PNU-2017-1555). The animal study was performed in accordance with the guidelines for animal experiments issued by PNU-IACUC.

These authors contributed equally to this work.

References

  • 1.Strmac M, Braunbeck T. Isolated hepatocytes of rainbow trout (Oncorhynchus mykiss) as a tool to discriminate between differently contaminated small river systems. Toxicol In Vitro. 2000;14:361–377. doi: 10.1016/S0887-2333(00)00031-X. [DOI] [PubMed] [Google Scholar]
  • 2.Ward R J, Zhang Y, Crichton R R. Aluminium toxicity and iron homeostasis. J Inorg Biochem. 2001;87:9–14. doi: 10.1016/S0162-0134(01)00308-7. [DOI] [PubMed] [Google Scholar]
  • 3.Gaetke L M, Chow C K. Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology. 2003;189:147–163. doi: 10.1016/S0300-483X(03)00159-8. [DOI] [PubMed] [Google Scholar]
  • 4.Ebrahimi R, et al. Effect of dietary lead on intestinal nutrient transporters mRNA expression in broiler chickens. Biomed Res Int. 2015;2015:149745. doi: 10.1155/2015/149745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Breton J, et al. Chronic ingestion of cadmium and lead alters the bioavailability of essential and heavy metals, gene expression pathways and genotoxicity in mouse intestine. Arch Toxicol. 2013;87:1787–1795. doi: 10.1007/s00204-013-1032-6. [DOI] [PubMed] [Google Scholar]
  • 6.Zhai Q, et al. Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier. Appl Environ Microbiol. 2016;82:4429–4440. doi: 10.1128/AEM.00695-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Liu Z, Chen B. Copper treatment alters the barrier functions of human intestinal Caco-2 cells: involving tight junctions and P-glycoprotein. Hum Exp Toxicol. 2004;23:369–377. doi: 10.1191/0960327104ht464oa. [DOI] [PubMed] [Google Scholar]
  • 8.Pineton de Chambrun G, et al. Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice. Mucosal Immunol. 2014;7:589–601. doi: 10.1038/mi.2013.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Al-Saleh I, et al. Exposure to heavy metals (lead, cadmium and mercury) and its effect on the outcome of in-vitro fertilization treatment. Int J Hyg Environ Health. 2008;211:560–579. doi: 10.1016/j.ijheh.2007.09.005. [DOI] [PubMed] [Google Scholar]
  • 10.Luszczek-Trojnar E, Drag-Kozak E, Szczerbik P, Socha M, Popek W. Effect of long-term dietary lead exposure on some maturation and reproductive parameters of a female Prussian carp (Carassius gibelio B.) Environ Sci Pollut Res Int. 2014;21:2465–2478. doi: 10.1007/s11356-013-2184-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Waseem N, Butt S A, Hamid S. Amelioration of lead induced changes in ovary of mice, by garlic extract. J Pak Med Assoc. 2014;64:798–801. [PubMed] [Google Scholar]
  • 12.Weber D N. Exposure to sublethal levels of waterborne lead alters reproductive behavior patterns in fathead minnows (Pimephales promelas) Neurotoxicology. 1993;14:347–358. [PubMed] [Google Scholar]
  • 13.Edens F W, Garlich J D. Lead-induced egg production decrease in Leghorn and Japanese quail hens. Poult Sci. 1983;62:1757–1763. doi: 10.3382/ps.0621757. [DOI] [PubMed] [Google Scholar]
  • 14.Kain K H, et al. The chick embryo as an expanding experimental model for cancer and cardiovascular research. Dev Dyn. 2014;243:216–228. doi: 10.1002/dvdy.24093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Wu T, et al. Fostering efficacy and toxicity evaluation of traditional Chinese medicine and natural products: Chick embryo as a high throughput model bridging in vitro and in vivo studies. Pharmacol Res. 2018;133:21–34. doi: 10.1016/j.phrs.2018.04.011. [DOI] [PubMed] [Google Scholar]
  • 16.Stern C D. The chick; a great model system becomes even greater. Dev Cell. 2005;8:9–17. doi: 10.1016/j.devcel.2004.11.018. [DOI] [PubMed] [Google Scholar]
  • 17.Vergara M N, Canto-Soler M V. Rediscovering the chick embryo as a model to study retinal development. Neural Dev. 2012;7:22. doi: 10.1186/1749-8104-7-22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Dastagir K, et al. Murine embryonic fibroblast cell lines differentiate into three mesenchymal lineages to different extents: new models to investigate differentiation processes. Cell Reprogram. 2014;16:241–252. doi: 10.1089/cell.2014.0005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Lee J H, Park J W, Kim S W, Park J, Park T S. C-X-C chemokine receptor type 4 (CXCR4) is a key receptor for chicken primordial germ cell migration. J Reprod Dev. 2017;63:555–562. doi: 10.1262/jrd.2017-067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Lu Y, et al. Induced pluripotency in chicken embryonic fibroblast results in a germ cell fate. Stem Cells Dev. 2014;23:1755–1764. doi: 10.1089/scd.2014.0080. [DOI] [PubMed] [Google Scholar]
  • 21.Hu X, et al. Activation of Toll-like receptor 3 inhibits Marek’s disease virus infection in chicken embryo fibroblast cells. Arch Virol. 2016;161:521–528. doi: 10.1007/s00705-015-2674-x. [DOI] [PubMed] [Google Scholar]
  • 22.Kang Y, et al. Newcastle disease virus infection in chicken embryonic fibroblasts but not duck embryonic fibroblasts is associated with elevated host innate immune response. Virol J. 2016;13:41. doi: 10.1186/s12985-016-0499-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Szmolka A, Wiener Z, Matulova M E, Varmuzova K, Rychlik I. Gene Expression Profiles of Chicken Embryo Fibroblasts in Response to Salmonella Enteriti-dis Infection. PLoS One. 2015;10:e0127708. doi: 10.1371/journal.pone.0127708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.de Graaf I A, et al. Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies. Nat Protoc. 2010;5:1540–1551. doi: 10.1038/nprot.2010.111. [DOI] [PubMed] [Google Scholar]
  • 25.Smith M C, Madec S, Coton E, Hymery N. Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro Combined Toxicological Effects. Toxins. 2016;8:94. doi: 10.3390/toxins8040094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Akbari P, et al. Deoxynivalenol: a trigger for intestinal integrity breakdown. FASEB J. 2014;28:2414–2429. doi: 10.1096/fj.13-238717. [DOI] [PubMed] [Google Scholar]
  • 27.Chen J, et al. Developmental lead acetate exposure induces embryonic toxicity and memory deficit in adult zebrafish. Neurotoxicol Teratol. 2012;34:581–586. doi: 10.1016/j.ntt.2012.09.001. [DOI] [PubMed] [Google Scholar]
  • 28.Muller Y M, Kobus K, Schatz J C, Ammar D, Nazari E M. Prenatal lead acetate exposure induces apoptosis and changes GFAP expression during spinal cord development. Ecotoxicol Environ Saf. 2012;75:223–229. doi: 10.1016/j.ecoenv.2011.08.004. [DOI] [PubMed] [Google Scholar]
  • 29.Gandley R, Anderson L, Silbergeld E K. Lead: male-mediated effects on reproduction and development in the rat. Environ Res. 1999;80:355–363. doi: 10.1006/enrs.1998.3874. [DOI] [PubMed] [Google Scholar]
  • 30.Dorostghoal M, Moazedi A A, Moattari M. Long-term Developmental Effects of Lactational Exposure to Lead Acetate on Ovary in Offspring Wistar Rats. Int J Fertil Steril. 2011;5:39–46. [PMC free article] [PubMed] [Google Scholar]
  • 31.Franks P A, Laughlin N K, Dierschke D J, Bowman R E, Meller P A. Effects of lead on luteal function in rhesus monkeys. Biol Reprod. 1989;41:1055–1062. doi: 10.1095/biolreprod41.6.1055. [DOI] [PubMed] [Google Scholar]
  • 32.Kang K S, et al. Spatial and temporal action of chicken primordial germ cells during initial migration. Reproduction. 2015;149:179–187. doi: 10.1530/REP-14-0433. [DOI] [PubMed] [Google Scholar]
  • 33.Fujimoto T, Ukeshima A, Kiyofuji R. The origin, migration and morphology of the primordial germ cells in the chick embryo. Anat Rec. 1976;185:139–145. doi: 10.1002/ar.1091850203. [DOI] [PubMed] [Google Scholar]
  • 34.Motono M, Ohashi T, Nishijima K, Iijima S. Analysis of chicken primordial germ cells. Cytotechnology. 2008;57:199–205. doi: 10.1007/s10616-008-9156-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Kunwar P S, Siekhaus D E, Lehmann R. In vivo migration: a germ cell perspective. Annu Rev Cell Dev Biol. 2006;22:237–265. doi: 10.1146/annurev.cellbio.22.010305.103337. [DOI] [PubMed] [Google Scholar]
  • 36.Dekel N, Gnainsky Y, Granot I, Mor G. Inflammation and implantation. Am J Reprod Immunol. 2010;63:17–21. doi: 10.1111/j.1600-0897.2009.00792.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Abrahams V M, Kim Y M, Straszewski S L, Romero R, Mor G. Macrophages and apoptotic cell clearance during pregnancy. Am J Reprod Immunol. 2004;51:275–282. doi: 10.1111/j.1600-0897.2004.00156.x. [DOI] [PubMed] [Google Scholar]
  • 38.Koga K, Mor G. Toll-like receptors at the maternal-fetal interface in normal pregnancy and pregnancy disorders. Am J Reprod Immunol. 2010;63:587–600. doi: 10.1111/j.1600-0897.2010.00848.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Thompson J G, Kind K L, Roberts C T, Robertson S A, Robinson J S. Epigenetic risks related to assisted reproductive technologies: short- and long-term consequences for the health of children conceived through assisted reproduction technology: more reason for caution? Hum Reprod. 2002;17:2783–2786. doi: 10.1093/humrep/17.11.2783. [DOI] [PubMed] [Google Scholar]
  • 40.Balaji S, et al. Chemokine Involvement in Fetal and Adult Wound Healing. Adv Wound Care (New Rochelle) 2015;4:660–672. doi: 10.1089/wound.2014.0564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Ding J, Tredget E E. The Role of Chemokines in Fi-brotic Wound Healing. Adv Wound Care (New Rochelle) 2015;4:673–686. doi: 10.1089/wound.2014.0550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Rees P A, Greaves N S, Baguneid M, Bayat A. Chemokines in Wound Healing and as Potential Therapeutic Targets for Reducing Cutaneous Scarring. Adv Wound Care (New Rochelle) 2015;4:687–703. doi: 10.1089/wound.2014.0568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Krimmling T, Beineke A, Schwegmann-Wessels C. Infection of porcine precision cut intestinal slices by transmissible gastroenteritis coronavirus demonstrates the importance of the spike protein for enterotropism of different virus strains. Vet Microbiol. 2017;205:1–5. doi: 10.1016/j.vetmic.2017.04.029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Li M, de Graaf I A, Groothuis G M. Precision-cut intestinal slices: alternative model for drug transport, metabolism, and toxicology research. Expert Opin Drug Metab Toxicol. 2016;12:175–190. doi: 10.1517/17425255.2016.1125882. [DOI] [PubMed] [Google Scholar]
  • 45.Niu X, de Graaf I A, van der Bij H A, Groothuis G M. Precision cut intestinal slices are an appropriate ex vivo model to study NSAID-induced intestinal toxicity in rats. Toxicol In Vitro. 2014;28:1296–1305. doi: 10.1016/j.tiv.2014.06.010. [DOI] [PubMed] [Google Scholar]
  • 46.Punyadarsaniya D, et al. Precision-cut intestinal slices as a culture system to analyze the infection of differentiated intestinal epithelial cells by avian influenza viruses. J Virol Methods. 2015;212:71–75. doi: 10.1016/j.jviromet.2014.10.015. [DOI] [PMC free article] [PubMed] [Google Scholar]

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