The Toxicologist - Society of Toxicology

UtSMCs. Phosphorylation of FoxO1 was largely abolished by 24 h following Fen
administration, and Fen induced increased association of FoxO1 and p27kip1 as
evidenced by immunoprecipitation in both cell lines. Overexpression of doxycycline-regulated
adenovirus p27kip1 (Ad.p27kip1) resulted in inhibition of proliferation
and markedly reduced mRNA and protein levels of CDK2 in both cell lines.
Fen was found to restore these effects, including cell growth with significantly increased
percentages of cells in S phase, but decreased percentages in G0-G1 phase.
Consequently, our results indicate that down-regulation of p27kip1 by Fen in
UtLM cells and UtSMCs is associated with decreases in FoxO1. This suggests that
FoxO1/p27kip1 could be a potential target pathway for Fen-induced cell proliferation
through the regulation of CDK2 and cell cycle progression, and may possibly
play a role in the pathogenesis of fibroids following environmental exposures.
1071 INVESTIGATING THE IMPACT OF CHRONIC
HERBICIDE EXPOSURE ON SEXUAL DEVELOPMENT
IN ZEBRAFISH.
M. M. Corvi 1 , K. A. Stanley 1 , J. K. LaDu 1 , T. S. Peterson 3 , S. W. Feist 2 , M. L.
Kent 2, 4 and R. L. Tanguay 1 . 1 Environmental and Molecular Toxicology, Oregon State
University, Corvallis, OR, 2 Weymouth Laboratory, Centre for Environment, Fisheries
& Aquaculture Science, Weymouth, United Kingdom, 3 Microbiology, Oregon State
University, Corvallis, OR and 4 Environmental Health Sciences Center, Oregon State
University, Corvallis, OR.
The potential effects of the herbicide atrazine (ATZ) on aquatic species are highly
controversial; some studies have reported that exposure to low ATZ concentrations
adversely impacts gonadal development and/or sexual differentiation in amphibians
and fish while others do not. A chronic study was performed investigating the potential
effects of ATZ on zebrafish (Danio rerio). Larval fish were exposed to nominal
concentrations of 0, 0.1, 1, 10 μM ATZ, or 1 nM 17beta-estradiol (E2) from
17-130 days post-fertilization (dpf). Treatment groups consisted of eight replicate
tanks with a total of 10 fish per tank. At study termination, body measurements
were taken; then fish were histologically processed. Slide sections for each fish were
examined to assign sex and evaluate potential impacts of E2 or ATZ on gonadal development.
Exposure to E2 resulted in a significantly higher proportion of females
to normal, mature fish, a greater percent of abnormally developed male fish, and
fish lacking differentiated gonadal tissue. In contrast, ATZ exposure did not influence
the percentages of female or male fish when compared to control. Estradiol
tanks had significantly larger male fish while 10 μM ATZ exposures resulted in
smaller zebrafish than their control counterparts. The study indicates that exposure
to 0.1, 1. 10 μM ATZ does not significantly impact zebrafish gonadal development
or sexual differentiation.
1072 CIGARETTE SMOKE CONDENSATE INHIBITS
FOLLICULAR DEVELOPMENT, OOCYTE
MATURATION, AND DYSREGULATES STEROIDS
SYNTHESIS IN VITRO: IMPLICATIONS FOR HUMAN
FECUNDITY.
J. Sadeu and W. G. Foster. Department of Obstetrics and Gynecology, McMaster
University, Hamilton, ON, Canada.
Decreased fertility and poorer response to ovulation induction have been reported
in women who smoke compared to non-smokers. The cytotoxic effects and underlying
mechanisms of action of cigarette smoke on ovarian function are poorly defined.
We therefore hypothesize that cigarette smoke condensate (CSC) will affect
follicular development, steroidogenesis, cumulus cell differentiation and oocyte
maturity. Isolated mouse follicles (100-130 μm) were cultured for 13 days (D13) in
the absence (controls) or presence of increasing CSC concentrations (30-130
μg/ml). Follicular development and viability were recorded prior to refreshment on
days 4 (D4), 8 (D8) and 12 (D12) of culture. On D12, follicle survival was determined
and preovulatory follicles stimulated with hCG and EGF. Following 18h
(D13) after stimulation, cumulus cell-oocyte complexes, oocyte diameter and nuclear
maturation were determined. Steroid output in spent media was measured
(ELISA) on D8 and D12 (E2), and D12 and D13 (P4). Follicular development significantly
(p