PMID- 11896295
OWN - NLM
STAT- MEDLINE
DCOM- 20020621
LR  - 20190513
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 66
IP  - 2
DP  - 2002 Apr
TI  - Developmental stage-specific effects of perinatal 
      2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on reproductive organs of male rat 
      offspring.
PG  - 283-92
AB  - Exposure to a relatively low dose of 2,3,7,8-tetrachlorodebenzo-p-dioxin (TCDD) 
      during mid-gestation induces a reduction of ventral prostate weight in rat 
      offspring. Recently we reported that a single administration of TCDD (12.5-800 
      ng/kg body weight) to pregnant Holtzman rats on gestational day (GD) 15 caused a 
      decrease in androgen receptor (AR) mRNA level in the ventral prostate during the 
      prepubertal period, and we proposed that this reduction of AR mRNA is one of the 
      most sensitive adverse endpoints due to perinatal exposure to TCDD (S. Ohsako et 
      al., 2001, TOXICOL: Sci. 60, 132-143). In the present study, to investigate the 
      mechanism of a decrease in AR mRNA level, we administered TCDD to rats at other 
      developmental stages and compared possible alterations of the male reproductive 
      system. Pregnant Sprague-Dawley rats were given a single oral dose of 1 microg 
      TCDD/kg body weight on GD 15 or GD 18, or male pups born from untreated dams were 
      subcutaneously given a single dose of 1 microg TCDD/kg body weight on postnatal 
      day 2 (PND 2). Offspring exposed on GD 15, GD 18, and PND 2 were sacrificed on 
      PND 70. TCDD exposure on GD 15 resulted in significant decreases in the 
      urogenital complex and ventral prostate weights and urogenital-glans penis length 
      of male rat offspring, but not on GD 18 and PND 2. Testicular and epididymal 
      weights were also lower than control group only in the TCDD-exposed GD 15 group. 
      Anogenital distance was significantly reduced in the TCDD-exposed GD 15 and GD 18 
      groups, but not in the TCDD-exposed PND 2 group. Semiquantitative RT-PCR analysis 
      showed that AR mRNA levels were decreased in the TCDD-exposed GD 15 group only, 
      and that the constitutive level of cytochrome P450 1A1 (CYP1A1) mRNA in the 
      ventral prostate was not changed by TCDD in any of the exposed groups. No changes 
      in AR mRNA level were detected in the testis or brain in any of the TCDD-exposed 
      groups. These results suggest the presence of a critical window during 
      development with regard to impairments of male reproductive organs by in utero 
      and lactational exposure to a low dose of TCDD.
FAU - Ohsako, Seiichiroh
AU  - Ohsako S
AD  - Molecular and Cellular Toxicology Section, Environmental Health Sciences 
      Division, Endocrine Disruptors and Dioxin Research Project, National Institute 
      for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan. 
      ohsako@nies.go.jp
FAU - Miyabara, Yuichi
AU  - Miyabara Y
FAU - Sakaue, Motoharu
AU  - Sakaue M
FAU - Ishimura, Ryuta
AU  - Ishimura R
FAU - Kakeyama, Masaki
AU  - Kakeyama M
FAU - Izumi, Hiroyuki
AU  - Izumi H
FAU - Yonemoto, Junzo
AU  - Yonemoto J
FAU - Tohyama, Chiharu
AU  - Tohyama C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Teratogens)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Female
MH  - Injections, Subcutaneous
MH  - Kidney/chemistry
MH  - Male
MH  - Organ Size
MH  - Polychlorinated Dibenzodioxins/pharmacokinetics/*toxicity
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Prostate/chemistry/*drug effects/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Androgen/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Teratogens/pharmacokinetics/*toxicity
MH  - Testis/*drug effects
EDAT- 2002/03/16 10:00
MHDA- 2002/06/22 10:01
CRDT- 2002/03/16 10:00
PHST- 2002/03/16 10:00 [pubmed]
PHST- 2002/06/22 10:01 [medline]
PHST- 2002/03/16 10:00 [entrez]
AID - 10.1093/toxsci/66.2.283 [doi]
PST - ppublish
SO  - Toxicol Sci. 2002 Apr;66(2):283-92. doi: 10.1093/toxsci/66.2.283.