Effects of in utero exposure to di(n-butyl) phthalate for estrogen receptors α, β, and androgen receptor of Leydig cell on rats.
Estrogens and androgens affect male and female reproductive systems. Recently, we reported that prenatal di(n-butyl) phthalate (DBP) exposure induced atypical Leydig cells (LCs) hyperplasia during adulthood. The present study investigated the expression of estrogen receptor α (ERα), estrogen receptor β (ERβ), and androgen receptor (AR) in LCs of 5-, 7-, 9-, 14-, and 17-week-old Sprague-Dawley (srl) rats whose dams had been administered DBP intragastrically at 100 mg/kg/day or the vehicle (corn oil) from days 12 to 21 postconception. Immunohistochemical, Western blotting, and reverse transcription polymerase chain reaction analyses revealed that the expressions of ERα, ERβ, and AR proteins and mRNAs in the DBP group were similar to those of the vehicle group at 5 and 7 weeks, but significantly higher ERα and lower ERβ and AR levels were observed in the DBP group at 9 to 17 weeks. The rats prenatally exposed to DBP had seminiferous tubule degeneration and atypical hyperplasia of LCs during adulthood, which was associated with an increase in expression of ERα and a decrease of ERβ and AR in the testis.
Department of Toxicology, Laboratory Animal Science and Veterinary Anatomy, Azabu University School of Veterinary Medicine, Kanagawa, Japan wakui@azabu-u.ac.jp.
Shin
S
Wakui
Department of Toxicology, Laboratory Animal Science and Veterinary Anatomy, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
Masaru
M
Shirai
Department of Toxicology, Laboratory Animal Science and Veterinary Anatomy, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
Masaya
M
Motohashi
Drug Safety Testing Center, Saitama, Japan.
Tomoko
T
Mutou
Drug Safety Testing Center, Saitama, Japan.
Noriko
N
Oyama
School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Michael F
MF
Wempe
Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
Hiroyuki
H
Takahashi
Department of Toxicology, Laboratory Animal Science and Veterinary Anatomy, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
Tomoo
T
Inomata
Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
Masahiro
M
Ikegami
J-Pharma Co., Ltd., Tokyo, Japan.
Hitoshi
H
Endou
Department of Toxicology, Laboratory Animal Science and Veterinary Anatomy, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
Masao
M
Asari
D000818:Animals; D003993:Dibutyl Phthalate / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011944:Receptors, Androgen; D003993:Dibutyl Phthalate
Leydig cell; androgen receptor; estrogen receptor α; estrogen receptor β; prenatal DBP exposure to rats; testis.