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Presence of Ribeiroia ondatrae in the developing anuran limb disrupts retinoic acid levels

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Abstract

The widespread reports of malformed frogs have sparked interest worldwide to try and determine the causes of such malformations. Ribeiroia ondatrae is a digenetic trematode, which has been implicated as one such cause, as this parasite encysts within the developing tadpole hind limb bud and inguinal region causing dramatic limb malformations. Currently, the mechanisms involved in parasite-induced limb deformities remain unclear. We sought to investigate whether the level of retinoic acid (RA), a morphogenetic factor known to play a critical role in limb bud formation, is altered by the presence of R. ondatrae within the infected tadpole. Alteration of RA levels within the limb bud caused by the presence of the parasite may be achieved in three ways. First, metacercariae are actively secreting RA; second, cercariae, upon entering the limb/inguinal region, may release a large amount of RA; finally, the metacercariae may induce either an increase in the synthesis or a decrease in the degradation of the host’s endogenous retinoic acid levels. Here, we show through high performance liquid chromatography and mass spectrometry that limb bud tissue of Lithobates sylvaticus, which has been parasitised, contains 70% more RA compared to the unparasitised control. Furthermore, parasites that have encysted within the limb buds appear to contain substantially less RA (56%) than the free swimming cercariae (defined as the infectious stage of the parasite). Taken together, these data illustrate for the first time that encystment of R. ondatrae leads to an increase in RA levels in the tadpole limb bud and may offer insight into the mechanisms involved in parasite-induced limb deformities.

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References

  • Biron DG, Marche L, Ponton F, Loxdale HD, Galeotti N, Renault L, Joly C, Thomas F (2005) Behavioural manipulation in a grasshopper harbouring hairworm: a proteomics approach. P Roy Soc B Biol Sci 272:2117–2126

    Article  CAS  Google Scholar 

  • Blaustein AR, Johnson PT (2003) The complexity of deformed amphibians. Front Ecol Environ 1:87–94

    Article  Google Scholar 

  • Bryant SV, Gardiner DM (1992) Retinoic acid, local cell–cell interactions, and pattern-formation in vertebrate limbs. Dev Biol 152:1–25

    Article  PubMed  CAS  Google Scholar 

  • Collins JP, Storfer A (2003) Global amphibian declines: sorting the hypotheses. Divers Distrib 9:89–98

    Article  Google Scholar 

  • Dalzell BJ, Sutherland DR (1998) Possibilities of Manodistomum syntomentera as a cause of deformities in Rana pipiens. Univ Wis Crosse J Undergrad Res 1:28–32

    Google Scholar 

  • Degitz SJ, Kosian PA, Makynen EA, Jensen KM, Ankley GT (2000) Stage- and species-specific developmental toxicity of all-trans retinoic acid in four native North American ranids and Xenopus laevis. Toxicol Sci 57:264–274

    Article  PubMed  CAS  Google Scholar 

  • Dmetrichuk JM, Carlone RL, Jones TRB, Vesprini ND, Spencer GE (2008) Detection of endogenous retinoids in the molluscan CNS and characterization of the trophic and tropic actions of 9-cis retinoic acid on isolated neurons. J Neurosci 28:13014–13024

    Article  PubMed  CAS  Google Scholar 

  • Elinson RP, Walton Z, Lee SY, Nath K (2008) Conservation in a frog of the retinoic acid requirement for forelimb initiation. Dev Biol 319:498

    Article  Google Scholar 

  • Fried B (1997) An overview of the biology of trematodes. In: Fried B, Graczyk TK (eds) Advances in trematode biology. CRC, Boca Raton, pp 12–13

    Google Scholar 

  • Gardiner D, Ndayibagira A, Grun F, Blumberg B (2003) Deformed frogs and environmental retinoids. Pure Appl Chem 75:2263–2273

    Article  CAS  Google Scholar 

  • Gosner KL (1960) A simplified table for staging anuran embryos and larvae with notes on identification. Herpetologica 16:183–190

    Google Scholar 

  • Huffman JE, Fried B (1990) Echinostoma and echinostomiasis. Adv Parasitol 29:215–269

    Article  PubMed  CAS  Google Scholar 

  • Johnson PTJ, Sutherland DR (2003) Amphibian deformities and Ribeiroia infection: an emerging helminthiasis. Trends Parasitol 19:332–335

    Article  PubMed  Google Scholar 

  • Johnson PTJ, Lunde KB, Ritchie EG, Launer AE (1999) The effect of trematode infection on amphibian limb development and survivorship. Science 284:802–804

    Article  PubMed  CAS  Google Scholar 

  • Johnson PTJ, Lunde KB, Thurman EM, Ritchie EG, Wray SN, Sutherland DR, Kapfer JM, Frest TJ, Bowerman J, Blaustein AR (2002) Parasite (Ribeiroia ondatrae) infection linked to amphibian malformations in the western United States. Ecol Monogr 72:151–168

    Article  Google Scholar 

  • Johnson PTJ, Sutherland DR, Kinsella JM, Lunde KB (2004) Review of the trematode genus Ribeiroia (Psilostomidae): Ecology, life history and pathogenesis with special emphasis on the amphibian malformation problem. Adv Parasitol 57:191–253

    Article  PubMed  Google Scholar 

  • Lee GS, Kochhar DM, Collins MD (2004) Retinoid-induced limb malformations. Curr Pharm Des 10:2657–2699

    Article  PubMed  CAS  Google Scholar 

  • Lewandoskia M, Mackem S (2009) Limb development: the rise and fall of retinoic acid. Curr Biol 19:R558–R561

    Article  Google Scholar 

  • Maden M (1983) The effect of vitamin-a on limb regeneration in Rana temporaria. Dev Biol 98:409–416

    Article  PubMed  CAS  Google Scholar 

  • Maden M (1996) Retinoic acid in development and regeneration. J Biosci 21:299–312

    Article  CAS  Google Scholar 

  • Maden M (1999) Heads or tails? Retinoic acid will decide. Bioessays 21:809–812

    Article  PubMed  CAS  Google Scholar 

  • Maden M (2007) Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci 8:755–765

    Article  PubMed  CAS  Google Scholar 

  • Maden M, Hind M (2003) Retinoic acid, a regeneration-inducing molecule. Dev Dyn 226:237–244

    Article  PubMed  CAS  Google Scholar 

  • Maden M, Sonneveld E, van der Saag PT, Gale E (1998) The distribution of endogenous retinoic acid in the chick embryo: implications for developmental mechanisms. Development 125:4133–4144

    PubMed  CAS  Google Scholar 

  • Mark M, Ghyselinck NB, Chambon P (2009) Function of retinoic acid receptors during embryonic development. Nucl Recept Signal 7:e002

    PubMed  Google Scholar 

  • Meteyer CU, Loeffler IK, Fallon JF, Converse KA, Green E, Helgen JC, Kersten S, Levey R, Eaton-Poole L, Burkhart JG (2000) Hind limb malformations in free-living northern leopard frogs (Rana pipiens) from Maine, Minnesota, and Vermont suggest multiple etiologies. Teratology 62:151–171

    Article  PubMed  CAS  Google Scholar 

  • Moore J (2002) Behavioral alterations and parasite transmission. In: May RM, Harvey PH (eds) Parasites and the behavior of animals. Oxford University Press, Oxford, pp 35–89

    Google Scholar 

  • Olsen OW (1974) Animal parasites: their life cycles and ecology, 3rd edn. University Park Press, Baltimore

    Google Scholar 

  • Rajakaruna RS, Piyatissa PMJR, Jayawardena UA, Navaratne AN, Amerasinghe PH (2008) Trematode infection induced malformations in the common hourglass treefrogs. J Zool 275:89–95

    Article  Google Scholar 

  • Scadding SR, Maden M (1986a) Comparison of the effects of vitamin-a on limb development and regeneration in Xenopus laevis tadpoles. J Embryol Exp Morphol 91:35–53

    PubMed  CAS  Google Scholar 

  • Scadding SR, Maden M (1986b) The effects of local application of retinoic acid on limb development and regeneration in tadpoles of Xenopus laevis. J Embryol Exp Morphol 91:55–63

    PubMed  CAS  Google Scholar 

  • Schotthoefer AM, Koehler AV, Meteyer CU, Cole RA (2003) Influence of Ribeiroia ondatrae (Trematoda: Digenea) infection on limb development and survival of northern leopard frogs (Rana pipiens): effects of host stage and parasite-exposure level. Can J Zool 81:1144–1153

    Article  Google Scholar 

  • Sessions SK, Ruth SB (1990) Explanation for naturally occurring supernumerary limbs in amphibians. J Exp Zool 254:38–47

    Article  PubMed  CAS  Google Scholar 

  • Sessions SK, Franssen RA, Horner VL (1999) Morphological clues from multilegged frogs: are retinoids to blame? Science 284:800–802

    Article  PubMed  CAS  Google Scholar 

  • Stopper GF, Hecker L, Franssen RA, Sessions SK (2002) How trematodes cause limb deformities in amphibians. J Exp Zool 294:252–263

    Article  PubMed  Google Scholar 

  • Szuroczki D, Richardson JML (2009) The role of trematode parasites in larval anuran communities: an aquatic ecologist's guide to the major players. Oecologia 161:371–385

    Article  PubMed  Google Scholar 

  • Thomas F, Adamo S, Moore J (2005) Parasitic manipulation: where are we and where should we go? Behav Process 68:185–199

    Article  Google Scholar 

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Acknowledgements

We would especially like to thank Alysen Lougheed for all of her help in the seemingly never ending snail hunt and preparation of samples and Amanda Lepp for her assistance in the earlier experimental design phase. We would also like thank Dr. Janet Koprivnikar for all of her valuable input on earlier drafts of the manuscript. This research was funded by the Department of Biological Sciences, Brock University and the Natural Sciences and Engineering Research Council (DG# 238373 to G.E.S and DG# 2802-07 to R.L.C).

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  1. Dorina Szuroczki

    Present address: Department of Ecology & Evolutionary Biology, University of Toronto, 25 Harbord Street, Toronto, ON, Canada, M5S 3G5

Authors and Affiliations

  1. Department of Biological Sciences, Brock University, 500, Glenridge Avenue, St. Catharines, ON, Canada, L2S 3A1

    Nicholas D. Vesprini, Gaynor E. Spencer & Robert L. Carlone

  2. Department of Chemistry, Brock University, 500, Glenridge Avenue, St. Catharines, ON, Canada, L2S 3A1

    Tim R. B. Jones

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  1. Dorina Szuroczki
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  2. Nicholas D. Vesprini
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  3. Tim R. B. Jones
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  4. Gaynor E. Spencer
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  5. Robert L. Carlone
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Corresponding author

Correspondence to Dorina Szuroczki.

Additional information

D. Szuroczki and N. D. Vesprini shared primary authorship as both parties contributed equally to every aspect of this research.

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Szuroczki, D., Vesprini, N.D., Jones, T.R.B. et al. Presence of Ribeiroia ondatrae in the developing anuran limb disrupts retinoic acid levels. Parasitol Res 110, 49–59 (2012). https://doi.org/10.1007/s00436-011-2451-z

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  • DOI: https://doi.org/10.1007/s00436-011-2451-z

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