PMID- 11222880
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20190513
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 60
IP  - 1
DP  - 2001 Mar
TI  - Maternal exposure to a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 
      suppressed the development of reproductive organs of male rats: dose-dependent 
      increase of mRNA levels of 5alpha-reductase type 2 in contrast to decrease of 
      androgen receptor in the pubertal ventral prostate.
PG  - 132-43
AB  - To assess the health risks associated with exposure to 
      2,3,7,8-tetrachlorodebenzo-p-dioxin (TCDD), we studied the effects of a 
      relatively low dose of TCDD on the male reproductive system of rats, using the 
      experimental protocol of T. A. Mably et al. (1992, Toxicol. Appl. Pharmacol. 114, 
      97-107, 108-117, 118-126), and searched for the most sensitive and reliable among 
      several indices of TCDD toxicity. Pregnant Holtzman rats were given a single oral 
      dose of 0, 12.5, 50, 200, or 800 ng TCDD/kg body weight on gestational day (GD) 
      15, and male offspring were sacrificed on postnatal day (PND) 49 or 120. GC-MS 
      analysis of the abdominal fat tissue and testis clearly showed increased amounts 
      of TCDD in these offspring. However, there was no TCDD effect on body weight of 
      offspring. There were no changes on testicular or epididymal weights by TCDD 
      administration, even at the 800-ng/kg dose in rats sacrificed on either PND 49 or 
      120. In addition, TCDD administration resulted in no changes in daily sperm 
      production or sperm reserve at any of the doses used. However, the weight of the 
      urogenital complex, including the ventral prostate, was significantly reduced at 
      doses of 200 and 800 ng TCDD/kg in rats sacrificed on PND 120. Moreover, the 
      anogenital distance (AGD) of male rats sacrificed on PND 120 showed a significant 
      decrease in the groups receiving doses greater than 50 ng TCDD/kg. TCDD 
      administration resulted in no apparent dose-dependent changes in levels of either 
      serum testosterone or luteinizing hormone. Interestingly, reverse 
      transcription-polymerase chain reaction (RT-PCR) analysis revealed that, in the 
      ventral prostates of the PND 49 group, TCDD administration resulted in both a 
      dose-dependent increase in 5alpha-reductase type 2 (5alphaR-II) mRNA level and a 
      dose-dependent decrease in androgen receptor (AR) mRNA level. These results 
      suggest that low-dose TCDD administration had a greater effect on the development 
      of the external genital organs and ventral prostate than on development of the 
      testis and other internal genital organs. Moreover, it is highly suggested that 
      the decrease in the size of the ventral prostate by maternal TCDD exposure might 
      be due to decreased responsiveness of the prostate to androgen due to an 
      insufficient expression level of androgen receptor during puberty.
FAU - Ohsako, S
AU  - Ohsako S
AD  - Environmental Health Sciences Division, National Institute for Environmental 
      Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-0053, Japan. ohsako@nies.go.jp
FAU - Miyabara, Y
AU  - Miyabara Y
FAU - Nishimura, N
AU  - Nishimura N
FAU - Kurosawa, S
AU  - Kurosawa S
FAU - Sakaue, M
AU  - Sakaue M
FAU - Ishimura, R
AU  - Ishimura R
FAU - Sato, M
AU  - Sato M
FAU - Takeda, K
AU  - Takeda K
FAU - Aoki, Y
AU  - Aoki Y
FAU - Sone, H
AU  - Sone H
FAU - Tohyama, C
AU  - Tohyama C
FAU - Yonemoto, J
AU  - Yonemoto J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Environmental Pollutants)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Androgen)
RN  - EC 1.3.99.5 (3-Oxo-5-alpha-Steroid 4-Dehydrogenase)
SB  - IM
MH  - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics/*metabolism
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Environmental Pollutants/pharmacokinetics/*toxicity
MH  - Female
MH  - Gas Chromatography-Mass Spectrometry
MH  - Male
MH  - Maternal Exposure
MH  - Polychlorinated Dibenzodioxins/pharmacokinetics/*toxicity
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Prostate/*drug effects/*metabolism/pathology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Androgen/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sexual Maturation/*drug effects
MH  - Sperm Count
MH  - Testis/metabolism/pathology
MH  - Tissue Distribution
EDAT- 2001/02/27 10:00
MHDA- 2001/05/22 10:01
CRDT- 2001/02/27 10:00
PHST- 2001/02/27 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/02/27 10:00 [entrez]
AID - 10.1093/toxsci/60.1.132 [doi]
PST - ppublish
SO  - Toxicol Sci. 2001 Mar;60(1):132-43. doi: 10.1093/toxsci/60.1.132.