PMID- 15710172
OWN - NLM
STAT- MEDLINE
DCOM- 20050408
LR  - 20151119
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 203
IP  - 2
DP  - 2005 Mar 1
TI  - Differences between rats and mice in the involvement of the aryl hydrocarbon 
      receptor in 4-vinylcyclohexene diepoxide-induced ovarian follicle loss.
PG  - 114-23
AB  - Repeated dosing with the occupational chemical 4-vinylcyclohexene diepoxide (VCD) 
      selectively depletes small pre-antral follicles in the ovaries of rats and mice 
      via apoptosis. The aryl hydrocarbon receptor (AhR) plays a role in mediating the 
      effects of several xenobiotics. Therefore, this study was designed to investigate 
      a potential role of the AhR in VCD-induced ovotoxicity. Female F344 rats, C57BL/6 
      mice, or AhR-deficient (-/-, AhRKO) mice were dosed daily (15 days) with vehicle, 
      VCD (80 mg/kg, i.p.) and/or the AhR antagonist, alpha-naphthoflavone (ANF; 80 
      mg/kg, i.p.). Compared with controls, VCD caused a 60% reduction (P < 0.05) in 
      primordial and primary follicles in mice and rats. Concurrent dosing with ANF 
      protected against the VCD-induced follicle loss in rats, but not in mice. As with 
      AhR-intact mice and rats, VCD induced a 70% loss (P < 0.05) of small pre-antral 
      follicles in AhRKO mice. AhR mRNA expression was increased (P < 0.05) by VCD 
      dosing in small pre-antral follicles isolated from ovaries of rats but not mice. 
      AhR protein in rats was increased by VCD dosing in oocyte nuclei in primordial 
      and primary follicles when measured by immunofluorescence and confocal 
      microscopy. In rat small pre-antral follicles, apoptosis-associated 
      caspase-3-like activity was increased (P < 0.05) by VCD treatment, decreased (P < 
      0.05) by ANF treatment, and unaffected by VCD plus ANF treatment. VCD had no 
      effect on expression of GST Ya1 or GST Ya2 mRNA or CYP 1A1 protein in rats. Taken 
      together, these findings demonstrate a difference between rats and mice in the 
      potential involvement of AhR as related to VCD-induced ovotoxicity. Whereas, AhR 
      appears to be involved in rats, no evidence for a similar role in mice was 
      obtained. Overall, these findings point out that there can be mechanistic species 
      differences in ovarian responses to xenobiotic chemicals.
FAU - Thompson, Kary E
AU  - Thompson KE
AD  - Department of Physiology, The University of Arizona, College of Medicine, Tucson, 
      AZ 85724-5051, USA.
FAU - Bourguet, Shannon M
AU  - Bourguet SM
FAU - Christian, Patricia J
AU  - Christian PJ
FAU - Benedict, Jamie C
AU  - Benedict JC
FAU - Sipes, I Glenn
AU  - Sipes IG
FAU - Flaws, Jodi A
AU  - Flaws JA
FAU - Hoyer, Patricia B
AU  - Hoyer PB
LA  - eng
GR  - ES06694/ES/NIEHS NIH HHS/United States
GR  - R01-ES08979/ES/NIEHS NIH HHS/United States
GR  - R01-ES09246/ES/NIEHS NIH HHS/United States
GR  - R01-HD38995/HD/NICHD NIH HHS/United States
GR  - T32 GM08400-10/GM/NIGMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Benzoflavones)
RN  - 0 (Carcinogens)
RN  - 0 (Cyclohexanes)
RN  - 0 (Cyclohexenes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Vinyl Compounds)
RN  - 596C064IG4 (4-vinyl-1-cyclohexene dioxide)
RN  - 604-59-1 (alpha-naphthoflavone)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Benzoflavones/pharmacology
MH  - Carcinogens/*toxicity
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cell Count
MH  - Cyclohexanes/*toxicity
MH  - Cyclohexenes
MH  - Female
MH  - Follicular Atresia/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microscopy, Confocal
MH  - Ovarian Follicle/*drug effects/metabolism
MH  - RNA, Messenger/analysis/metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, Aryl Hydrocarbon/analysis/*antagonists & inhibitors/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Species Specificity
MH  - Vinyl Compounds/*toxicity
EDAT- 2005/02/16 09:00
MHDA- 2005/04/09 09:00
CRDT- 2005/02/16 09:00
PHST- 2004/05/12 00:00 [received]
PHST- 2004/07/26 00:00 [accepted]
PHST- 2005/02/16 09:00 [pubmed]
PHST- 2005/04/09 09:00 [medline]
PHST- 2005/02/16 09:00 [entrez]
AID - S0041-008X(04)00362-X [pii]
AID - 10.1016/j.taap.2004.07.010 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2005 Mar 1;203(2):114-23. doi: 
      10.1016/j.taap.2004.07.010.