PMID- 17218470
OWN - NLM
STAT- MEDLINE
DCOM- 20070730
LR  - 20131121
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 96
IP  - 2
DP  - 2007 Apr
TI  - Prenatal testosterone exposure permanently masculinizes anogenital distance, 
      nipple development, and reproductive tract morphology in female Sprague-Dawley 
      rats.
PG  - 335-45
AB  - In mammals, abnormal increases in fetal androgens disrupt normal development of 
      the female phenotype. Due to the recent concern regarding environmental 
      androgen-active chemicals, there is a need to identify sources of fetal androgen 
      variation and sensitive developmental markers for androgenic activity in female 
      rats. Anogenital distances (AGD), nipple retention, reproductive tract, and 
      external genitalia are morphological parameters organized by prenatal androgens 
      and are predictive of altered masculinized/defeminized phenotype in adult female 
      mice and rats. The objectives of this study were to (1) characterize the natural 
      prenatal androgen environment of rats including the magnitude of the intrauterine 
      position (IUP) effect, (2) characterize the permanent effects of prenatal 
      androgen exposure on female rats, and (3) determine the ability of AGD and 
      areolas to predict these permanent androgenic alterations in female rats. 
      Untreated male fetal rats had higher tissue testosterone (T) concentrations than 
      females in the amniotic fluid, reproductive tract, gonad, and fetal body. The 
      intrauterine position (IUP) of male and female fetuses did not affect T 
      concentrations or AGD in male or female rats at gestational day (GD) 22. Female 
      offspring exposed to 0, 1.5, and 2.5 mg/kg/day testosterone propionate (TP) on 
      GDs 14-18 displayed increased AGD at postnatal day (PND) 2 and decreased nipples 
      at PND 13 and as adults. TP-induced changes in neonatal AGD and infant areola 
      number were reliable indicators of permanently altered adult phenotype in female 
      rats. Further, females in the two high-dose groups displayed increased incidences 
      of external genital malformations and the presence of prostatic tissue, not 
      normally found in female rats.
FAU - Hotchkiss, Andrew K
AU  - Hotchkiss AK
AD  - Department of Zoology, North Carolina State University, Raleigh, North Carolina 
      27695, USA.
FAU - Lambright, Christy S
AU  - Lambright CS
FAU - Ostby, Joseph S
AU  - Ostby JS
FAU - Parks-Saldutti, Louise
AU  - Parks-Saldutti L
FAU - Vandenbergh, John G
AU  - Vandenbergh JG
FAU - Gray, Leon E Jr
AU  - Gray LE Jr
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070111
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Endocrine Disruptors)
RN  - 3XMK78S47O (Testosterone)
SB  - IM
MH  - Abnormalities, Drug-Induced/etiology/pathology
MH  - Anal Canal/abnormalities/*drug effects
MH  - Animals
MH  - Animals, Newborn/abnormalities
MH  - Endocrine Disruptors/chemistry/toxicity
MH  - Estrus/drug effects/physiology
MH  - Female
MH  - Fetus/abnormalities/drug effects
MH  - Genitalia, Female/abnormalities/*drug effects
MH  - Gestational Age
MH  - Male
MH  - Nipples/*drug effects/embryology/growth & development
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Testosterone/chemistry/*toxicity
MH  - Uterus/abnormalities/drug effects
MH  - Vagina/abnormalities/drug effects
MH  - Weight Loss/drug effects
EDAT- 2007/01/16 09:00
MHDA- 2007/07/31 09:00
CRDT- 2007/01/16 09:00
PHST- 2007/01/16 09:00 [pubmed]
PHST- 2007/07/31 09:00 [medline]
PHST- 2007/01/16 09:00 [entrez]
AID - kfm002 [pii]
AID - 10.1093/toxsci/kfm002 [doi]
PST - ppublish
SO  - Toxicol Sci. 2007 Apr;96(2):335-45. doi: 10.1093/toxsci/kfm002. Epub 2007 Jan 11.