Endocrine back ground on flutamide-induced hypospadias in rats

• Project/Area Number: 24510082
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Tottori University
• Principal Investigator: OHTA YASUHIKO 鳥取大学, 農学部, 教授 (60069078)
• Co-Investigator(Renkei-kenkyūsha): IGUCHI Taisen 大学共同利用機関法人自然科学研究機構, 岡崎統合バイオサイエンスセンター, 教授 (90128588)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 尿道下裂 / 内分泌かく乱 / アンチアンドロゲン / フルタミド / 生殖器異常 / ラット

Outline of Final Research Achievements

Morphogenesis and endocrine back ground on flutamide-induced hypospadias were examined in male rats. Measurement of a major component of phallus revealed that males given flutamide mimicked a female type during fetal development, and showed no sign of hyposperdias on the day of birth. Hypospadias was evident after 40 days of age. These abnormal developments were elicited in neonates, indicating that flutamide exposure in utero induces malformation of male type reproductive tract in adition to hypospadias in later ages. When the flutamide-treated rats were castrated on 10 days, hypospadias was no longer evident in adulthood, bearing female type of the genitalia. Those given testosterone after the castration exhibited hyposphadias. Serum level of testosterone was not different between the fluatamide-treated and control males. The present study reveals that androgen titer from testes after puberty play an important role on induction of hypospadias in male rats given flutamide in utero.

Research Products

• [Journal Article] Development of reproductive organs in the ivory shell Babylonia japonica: Observations from wild populations and laboratory-reared juveniles (2014)
  • Author(s): Horiguchi T, Ohta Y, Hamada F, Urushitani H, Cho H.S, Shiraishi H
  • Journal Title: Marine Environmental Research Volume: 93 Pages: 4-14
  • DOI: 10.1016/j.marenvres.2013.07.003
  • Peer Reviewed / Open Access
• [Journal Article] Differing species responsiveness of estrogenic contaminants in fish is conferred by the ligand binding domain of the estrogen receptor (2014)
  • Author(s): Miyagawa, S., Lange, A., Hirakawa, I., Tohyama, S., Ogino, Y., Mizutani, T., Kagami, Y., Kusano, T., Ihara, M., Tanaka, H., Tatarazako, N., Ohta, Y., Katsu, Y., Tyler, C.R. and Iguchi, T.
  • Journal Title: Environ. Sci. Technol. Volume: 未定 Issue: 9 Pages: 5254-5263
  • DOI: 10.1021/es5002659
  • Peer Reviewed / Open Access
• [Journal Article] Sugar expression in the mucosae of the canine uterus and vagina during the oestrous cycle and with pyometa (2013)
  • Author(s): Yasunga, Y., Takeuchi, t., Shimokawa, T., Asano,A., Nabeta, M.and Ohta,Y.
  • Journal Title: Vet. J. Volume: 196 Issue: 1 Pages: 116-118
  • DOI: 10.1016/j.tvjl.2012.08.008
  • Peer Reviewed
• [Journal Article] Establishment of transactivation assay systems using fish, amphibian, reptilian and human thyroid hormone receptors (2013)
  • Author(s): Oka, T., Mitsui-Watanabe, N., Tatarazako, N., Onishi, Y., Katsu, Y., Miyagawa, S., Ogino, Y., Yatsu, R., Kohno, S., Takase, M., Kawashima, Y., Aoki, Y., Guillette, L.J.Jr. and Iguchi, T.
  • Journal Title: J. Appl. Toxicol Volume: 33 Issue: 9 Pages: 991-1000
  • DOI: 10.1002/jat.2825
  • Peer Reviewed
• [Journal Article] Wnt family genes and their modulation in the ovary-independent and persistent vaginal epithelial cell proliferation and keratinization induced by neonatal diethylstilbestrol exposure in mice. (2012)
  • Author(s): Nakamura T, Miyagawa S, Katsu Y, Watanabe H, Mizutani T, Sato T, Morohashi KI, Takeuchi T, Iguchi T, Ohta Y
  • Journal Title: Toxicology Volume: 296 Issue: 1-3 Pages: 13-19
  • DOI: 10.1016/j.tox.2012.02.010
  • Peer Reviewed
• [Presentation] Malformation of reproductive tracts in male rats given flutamide in utero (2014)
  • Author(s): Ohta, Y., Miyagawa, S. and Iguchi, T.
  • Organizer: SETAC Europe 2014
  • Place of Presentation: Basel, Switzerland
  • Year and Date: 2014-05-11 – 2014-05-15
• [Presentation] External genitalia development in male and female rats given flutamide in utero (2013)
  • Author(s): Ohta, Y., Miyagawa, S. and Iguchi, T.
  • Organizer: SETAC Eurpoe2013
  • Place of Presentation: コンベンションセンター(連合王国グラスゴー）
• [Presentation] 妊娠中に投与したフルタミドの雄ラット生殖輸管系への影響 (2013)
  • Author(s): 太田康彦・村田清香・宮川信一・井口泰泉
  • Organizer: 環境ホルモン学会第16回研究発表会
  • Place of Presentation: 東京大学山上会館（東京都）
• [Presentation] 妊娠中にフルタミドを投与した雄ラットの生殖器異常について (2012)
  • Author(s): 村田清香・竹内崇師・太田康彦・平川育美・保永洋平・宮川信一・井口泰泉
  • Organizer: 環境ホルモン学会
  • Place of Presentation: 東京大学 山上会館