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Localization of Eutr2, a locus controlling susceptibility to DES-induced uterine inflammation and pyometritis, to RNO5 using a congenic rat strain

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Abstract

In some rat strains chronic administration of exogenous estrogens induces pyometritis, an inflammation of the uterus associated with infection, suggesting that there is genetic variation in susceptibility to estrogen-induced inflammation and pyometritis. In this article we report that following 10 weeks of treatment with the synthetic estrogen diethylstilbestrol (DES), Fisher 344 (F344) rats exhibit modest uterine inflammation and a 0% incidence of pyometritis. By contrast, under identical experimental conditions, Brown Norway (BN) rats exhibit significant inflammation and a 100% incidence of pyometritis. Similarly, we also observed profound uterine inflammation and a 100% incidence of pyometritis in a congenic rat strain in which a segment of RNO5 from the BN strain is carried on the F344 strain. These data suggest that a locus on RNO5 controls both the magnitude of DES-induced uterine inflammation and susceptibility to DES-induced pyometritis. This locus, designated Eutr2, resides within the same segment of RNO5 as the Eutr1 locus, which confers susceptibility to E2-induced pyometritis in an F2 population generated in a cross between the BN and August × Copenhagen 9935, Irish (ACI) strains.

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References

  • Armstrong DT (1968) Hormonal control of uterine lumen fluid retention in the rat. Am J Physiol 214: 764–771

    PubMed  CAS  Google Scholar 

  • Burrows H (1935) Leucocytic invasion as an accompaniment of epithelial metaplasia. J Pathol Bacteriol 41: 43–49

    Google Scholar 

  • Elwood W, Barnes PJ, Chung KF (1992) Airway hyperresponsiveness is associated with inflammatory cell infiltration in allergic brown-Norway rats. Int Arch Allergy Immunol 99: 91–97

    Article  PubMed  CAS  Google Scholar 

  • Gould KA, Pandey J, Lachel CM, Murrin CR, Flood LA, (2005) Genetic mapping of Eutr1, a locus controlling E2-induced pyometritis in the Brown Norway rat, to RNO5. Mamm Genome 16: 854–864

    CAS  PubMed  Google Scholar 

  • Griffith JS, Jensen SM, Lunceford JK, Kahn MW, Zheng Y, et al. (1997) Evidence for the genetic control of estradiol-regulated responses. Implications for variation in normal and pathological hormone-dependent phenotypes. Am J Pathol 150: 2223–2230

    PubMed  CAS  Google Scholar 

  • Holtzman S, Stone JP, Shellabarger CJ (1979) Synergism of diethylstilbestrol and radiation in mammary carcinogenesis in female F344 rats. J Natl Cancer Inst 63: 1071–1074

    PubMed  CAS  Google Scholar 

  • Larsen B, Markovetz AJ, Galask RP (1977) Role of estrogen in controlling the genital microflora of female rats. Appl Environ Microbiol 34: 534–540

    PubMed  CAS  Google Scholar 

  • Lee YH, Howe RS, Sha SJ, Teuscher C, Sheehan DM, et al. (1989) Estrogen regulation of an eosinophil chemotactic factor in the immature rat uterus. Endocrinology 125: 3022–3028

    PubMed  CAS  Google Scholar 

  • Pandey J, Bannout A, Wendell DL (2004) The Edpm5 locus prevents the ‘angiogenic switch’ in an estrogen-induced rat pituitary tumor. Carcinogenesis 10: 1829–1838

    Google Scholar 

  • Perez MC, Furth EE, Matzumura PD, Lyttle CR (1996) Role of eosinophils in uterine responses to estrogen. Biol Reprod 54: 249–254

    Article  PubMed  CAS  Google Scholar 

  • Roper RJ, Griffith JS, Lyttle CR, Doerge RW, McNabb AW, et al. (1999) Interacting quantitative trait loci control phenotypic variation in murine estradiol-regulated responses. Endocrinology 140: 556–561

    Article  PubMed  CAS  Google Scholar 

  • Singh P, Daniels M, Winsett DW, Richards J, Doerfler D, et al. (2003) Phenotypic comparison of allergic airway responses to house dust mite in three rat strains. Am J Physiol Lung Cell Mol Physiol 284: L588–L598

    PubMed  CAS  Google Scholar 

  • Stone JP, Holtzman S, Shellabarger CJ (1979) Neoplastic responses and correlated plasma prolactin levels in diethylstilbestrol-treated ACI and Sprague-Dawley rats. Cancer Res 39: 773-778

    PubMed  CAS  Google Scholar 

  • Tchernitchin A, Roorijck J, Tchernitchin X, Vandenhende J, Galand F (1974) Dramatic early increase in uterine eosinophils after oestrogen administration. Nature 248: 142–143

    Article  PubMed  CAS  Google Scholar 

  • Tchernitchin A, Tchernitchin X, Galand P (1975) Correlation of estrogen-induced uterine eosinophilia with other parameters of estrogen stimulation, produced with estradiol-17beta and estriol. Experientia 31: 993–994

    PubMed  CAS  Google Scholar 

  • Wendell DL, Gorski J (1997) Quantitative trait loci for estrogen-dependent pituitary tumor growth in the rat. Mamm Genome 8: 823–829

    Article  PubMed  CAS  Google Scholar 

  • Wendell DL, Daun SB, Stratton MB, Gorski J (2000) Different functions of QTL for estrogen-dependent tumor growth of the rat pituitary. Mamm Genome 11: 855–861

    Article  PubMed  CAS  Google Scholar 

  • Zondek B (1937) The effect of long-continued large doses of follicle hormone upon the uterus of the rat. Am J Obstet Gynecol 33: 979–988

    Google Scholar 

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Acknowledgments

The authors gratefully acknowledge Phillip Doyle for technical assistance. Financial support was provided by Oakland University Research in Excellence Program in Biotechnology and by the National Institutes of Health grant R01-CA71911.

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Correspondence to Karen A. Gould.

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Jyotsna Pandey, Karen A. Gould contributed equally to this work.

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Pandey, J., Gould, K.A., McComb, R.D. et al. Localization of Eutr2, a locus controlling susceptibility to DES-induced uterine inflammation and pyometritis, to RNO5 using a congenic rat strain. Mamm Genome 16, 865–872 (2005). https://doi.org/10.1007/s00335-005-0071-6

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  • DOI: https://doi.org/10.1007/s00335-005-0071-6

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