Fertility and developmental toxicity assessment in rats and rabbits with LY500307, a selective estrogen receptor beta (ERβ) agonist

Birth Defects Research Part B - Developmental and Reproductive Toxicology

Volumn 98, Issue 5, 2013, Pages 400-415

  Hilbish, Kim G ^a   Breslin, William J ^a   Johnson, Jason T ^a   Sloter, Eddie D ^b  

^a ELI LILLY AND COMPANY   (United States)

^b WIL RESEARCH LABORATORIES   (United States)

Author keywords

Development; Estrogen; Fertility; Fetus

Indexed keywords

ERTEBEREL;

ABORTION; ANIMAL EXPERIMENT; ARTICLE; AUTOPSY; BODY WEIGHT; COHABITATION; CONCEPTION; CONTROLLED STUDY; DEVELOPMENTAL TOXICITY; DIESTRUS; ENVIRONMENTAL EXPOSURE; ESTRUS CYCLE; FEMALE; FEMALE FERTILITY; FETAL WELL BEING; FETUS WEIGHT; FOOD INTAKE; GESTATIONAL AGE; HISTOPATHOLOGY; MALE; MALE FERTILITY; MATERNAL MORBIDITY; MATERNAL MORTALITY; MATING; MORPHOLOGY; NONHUMAN; ORGAN WEIGHT; PRIORITY JOURNAL; RABBIT; RAT; REPRODUCTION; SKELETON; SPERM; SPERMATOZOON DENSITY; TOXICOKINETICS;

ANIMALIA; ORYCTOLAGUS CUNICULUS; RATTUS;

DEVELOPMENT; ESTROGEN; FERTILITY; FETUS;

ANIMALS; BENZOPYRANS; BODY WEIGHT; DOSE-RESPONSE RELATIONSHIP, DRUG; EMBRYONIC DEVELOPMENT; ESTROGEN RECEPTOR BETA; FEMALE; FERTILITY; FETAL DEVELOPMENT; MALE; PREGNANCY; RABBITS; RATS; RATS, SPRAGUE-DAWLEY; REPRODUCTION;

EID: 84890311217     PISSN: 15429733     EISSN: 15429741     Source Type: Journal    
DOI: 10.1002/bdrb.21083     Document Type: Article

References (52)

1. Barkhem T, Carlsson B, Nilsson Y, Enmark E, Gustafsson J, Nilsson S. 1998. Differential response of estrogen receptor alpha and estrogen receptor beta to partial estrogen agonists/antagonists. Mol Pharmocol 54:105-112.
2. Bartholomeusz RK, Bruce NW, Lynch AM. 1999. Embryo survival, and fetal and placental growth following elevation of maternal estradiol blood concentrations in the rat. Biology of Reproduction 61(1):46-50.
3. Biegel L, Flaws J, Hirshfield A, O'Conner J, Elliott G, Ladics G, Silbergeld E, van Pelt C, Hurtt M, Cook J, Frame S. 1998. 90-day feeding and one-generation reproduction study in CRL:CD BR rats with 17β-estradiol. Toxicol Sci 44:116-142.
4. Carney EW, Kimmel CA. 2007. Interpretation of skeletal variations for human risk assessment: delayed ossification and wavy ribs. Birth Defects Res B 80:473-496.
5. Chapin R, Gulati D, Barenes K, Teague J. 1993. The effects of feed restriction on reproductive function of Sprague-Dawley rats. Fundam Appl Toxicol 20:23-29.
6. Couse J, Korach K. 1999. Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev 20:358-417.
7. Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS. 1997. Tissue distribution and quantitative analysis of estrogen receptor-α and estrogen receptor-β messenger ribonucleic acid in the wild-type and ERα-knockout mouse. Endocrinology 138(11):4613-4621.
8. Dawson, AB. 1926. A note on the staining of the skeleton of cleared specimens with Alizarin Red S. Stain Technol 1:123-124.
9. Delclos KB, Bucci TJ, Lomax LG, Latendresse JR, Warbritton A, Weis CC, Newbold RR. 2001. Effect of dietary genistein exposure during development on male and female CD (Sprague-Dawley) rats. Reprod Toxicol 15:647-663.
10. Dunn OJ. 1964. Multiple comparisons using rank sums. Technometrics 6(3):241-252.
11. Dunnett CW. 1964. New tables for multiple comparisons with a control. Biometrics 20:482-491.
12. Eddy E, Washburn T, Bunch D, Goulding E, Gladen B, Lubahn D, Korach K. 1996. Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 137:4796-4805.
13. Fleeman T, Cappon G, Chapin R, Hurtt M. 2005. Effects of feed restriction during organogenesis on embryo-fetal development in the rat. Birth Defects Res B 74:442-449.
14. Gill-Sharma MK, Dsouza S, Padwal V, Balasinor N, Aleem M, Parte P, Juneja HS. 2001. Antifertility effects of estradiol in adult male rats. J Endocrinol Invest 24(8):598-607.
15. Gray A, Feldman H, McKinlay J, Longcope C. 1991. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts male aging study. J Clin Endocrinol Metab 73(5):1016-1025.
16. Greene GL, Gilna P, Waterfiled M, Baker A, Hort Y, Shine J. 1986. Sequence and expression of human estrogen receptor complementary DNA. Science 231:1150-1154.
17. Harmen SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. 2001. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 66(2):724-731.
18. Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, Tujague M, Strom A, Treuter E, Warner M, Gustafsson J. 2007. Estrogen receptors: how do they signal and what are their targets? Physiol Rev 87:905-931.
19. Hiroi H, Inoue S, Watanabe T, Goto W, Orimo A, Momoeda M, Tsutsumi O, Taketani Y, Muramatsu M. 1999. Differential immunolocalization of estrogen receptor -α and-β in rat ovary and uterus. J Mol Endocrinol 22:37-44.
20. Hollander M, Wolfe DA. 1999. Nonparametric statistical methods. 2nd ed. New York, NY: John Wiley and Sons; 468p.
21. Hussain S, Lawrence MG, Taylor RA, Lo CY, A.P.C. BioResource, Frydenberg M, Ellem SJ, Furuc L, Risbridger GP. 2012. Estrogen receptor β activation impairs prostatic regeneration by inducing apoptosis in murine and human stem/progenitor enriched cell populations. PLoS ONE [Electronic Resources] 7(7):e40732
22. Imamov O, Morani A, Shim G, Omoto Y, Thulin-Anderson C, Warner M, Gustafsson J. 2004. Estrogen receptor β regulates epithelial cellular differentiation in the mouse ventral prostate. Proc Natl Acad Sci USA 101:9375-9380.
23. International Conference on Harmonisation. 2005. ICH harmonized tripartite guideline - detection of toxicity to reproduction of medicinal products and toxicity to male fertility S5 (R2). Available at: http://www.ich.org/fileadmin/public_web_site/guidelines/safety/S5_R2/step4/S5_R2.Guideline.pdf. Accessed 12 August 2013.
24. Kast A. 1994. Wavy ribs. A reversible pathologic finding in rat fetuses. Exp Toxicol Pathol 46:203-210.
25. Katzenellenbogen JA, Katzenellenbogen BS. 1996. Nuclear hormone receptros: ligand-activated regulators of transcription and diverse cell responses. Chem Biol 3:529-536.
26. Katzenellenbogen BS, Choi I, Delage-Mourroux R, Ediger T, Martini P, Montano M, Sun J, Weis K, Katzenellenbogen JA. 2000. Molecular mechanisms of estrogen action: selective ligands and receptor pharmacology. J Steroid Biochem Mol Biol 74:279-285.
27. Khera K, Whalen C, Trivett G. 1978. Teratogenicity studies on linuron, malathion, and methoxychlor in rats. Toxicol Appl Pharmacol 45:435-444.
28. Korach KS, Couse JF, Curtis SW, Washbutn TF, Lindzey J, Kimbro KS, Eddy EM, Migliaccio S, Snedeker SM, Lubahn DB, Schomberg DW, Smith EP. 1996. Estrogen receptor gene disruption: molecular characterization and experimental and clinical phenotypes. Recent Prog Horm Res 51:159-186.
29. Kruskal WH, Wallis WA. 1952. Use of ranks in one-criterion variance analysis. J Am Stat Assoc 47:583-621.
30. Kuiper G, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson J. 1996. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93:5925-5930.
31. Kuiper G, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA. 1997. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endorcrinology 138:863-870.
32. Matthew J, Gustafsson J. 2003. Estrogen signaling: a subtle balance between, ERα and ERβ. Mol Interv 3:281-292.
33. McClain RM, Wolz E, Davidovish A, Edwards J, Bausch J. 2007. Reproductive safety studies with genistein in rats. Food Chem Toxicol Aug 45(8):1319-1332.
34. McPherson S, Ellem S, Simpson E, Patchev V, Fritzemeier KH, Risbridger G. 2007. Essential role for estrogen receptor β in stromal-epithelial regulation of prostatic hyperplasia. Endocrinology 148(2):566-574.
35. McPherson S, Hussain S, Balanathan P, Hedwards S, Niranjan B, Grant M, Chandrasiri U, Toivanen R, Wang Y, Taylor R, Risbridger G. 2010. Estrogen receptor-beta activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNF alpha mediated. Proc Natl Acad Sci USA 107(7):3123-3128.
36. Mosselman S, Polman J, Dijkema R. 1996. ERβ: identification and characterization of a novel human estrogen receptor. FEBS Lett 392:49-53.
37. Nishimura M, Lizuka M, Iwaki S, Kast A. 1982. Repairability of drug induced "wavy ribs" in rat offspring. Arzneimittelforschung 32:1518-1522.
38. National Toxicology Program. 2008. Multigenerational reproductive toxicology study of genistein in Sprague-Dawley rats. NTP Technical Report, NIH, Research Triangle Park, NC. Publication No. 08-4477.
39. Norman B, Dodge J, Richardson T, Borromeo P, Lugar C, Jones S, Chen K, Wang Y, Durst G, Barr R, Montrose-Rafizadeh C, Osbone H, Amos R, Guo S, Boodhoo A, Krishman V. 2006. Benzopyrans are selective estrogen receptor β agonists with novel activity in models of benign prostatic hyperplasia. J Med Chem 49:6155-6157.
40. Ogawa S, Lubahn D, Korach K, Pfaff D. 1997. Behavioral effects of estrogen receptor gene disruption in male mice. Proc Natl Acad Sci USA 94:1476-1481.
41. Pace P, Taylor J, Suntharalingam S, Coombes RC, Ali S. 1997. Human estrogen receptor β binds DNA in a manner similar to and dimerizes with estrogen receptor α. J Biol Chem 272:25832-25838.
42. Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson JA, Kushner PJ, Scanlan TS. 1997. Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites. Science 277:1508-1510.
43. SAS® Proprietary Software, version 8.2, SAS Institute: Cary, NC, 1999-2001.
44. Snedecor GW, Cochran WG. 1980. One-way classifications; analysis of variance. In:, editors. Statistical methods. 7th ed. Ames, IA: The Iowa State University Press. p 215-237.
45. Stuckhardt JL, Poppe SM. 1984. Fresh visceral examination of rat and rabbit fetuses used in teratogenicity testing. Teratog Carcinog Mutagen 4:181-188.
46. Uson A, Paez A, Uson-Jaeger J. 1991. The natural history and course of untreated benign prostatic hyperplasia. Eur Urol 20(suppl 2):22-26.
47. Verhamme KMC, Dieleman JP, Bleumink GS, van der Lei J, Sturkenboom MCJM. 2002. Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care-the triumph project. Eur Urol 42:323-328.
48. Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg L. 2002. Estradiol in elderly men. Aging Male 5(2):98-102.
49. Wasserman NF. 2006. Benign prostatic hyperplasia: a review and ultrasound classification. Radio Clin N Am 44:689-710.
50. Weihua Z, Lathe R, Warner M, Gustafsson J. 2002. An endocrine pathway in the prostate, ERβ, AR, 5α-androstane-3β, 17β-diol, and CYP7B1, regulates prostate growth. Proc Natl Acad Sci USA 99:13589-13594.
51. Wilson, JG. 1965. Embryological considerations in teratology. In: Wilson JG, Warkany J, editors. Teratology: Principles and Techniques. Chicago, IL: University of Chicago Press. p 251-277.
52. Woo DC, Hoar RM. 1972. Apparent hydronephrosis as a normal aspect of renal development in late gestation of rats: the effect of methyl salicylate. Teratology 6:191-196.