TY - JOUR
T1 - Effect of chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin in female rats on ovarian gene expression
AU - Valdez, Kelli E.
AU - Shi, Zhanquan
AU - Ting, Alison Y.
AU - Petroff, Brian K.
N1 - Funding Information:
This study was supported by the United States National Institutes of Health (NIH/NIEHS ES012916, BKP), the NIH Center for Reproductive Sciences, University of Kansas Medical Center, and the University of Virginia NIH Center for Research in Reproduction Ligand Analysis. We are grateful for the assistance of Dr. Stanislav Svojanovsky, KUMC Bioinformatics Core, and Clark Bloomer, KUMC Microarray facility. We also thank Steve Gum for technical assistance.
PY - 2009/7
Y1 - 2009/7
N2 - The aryl hydrocarbon receptor (AHR) mediates the effects of many endocrine disruptors and contributes to the loss of fertility in polluted environments. Female rats exposed chronically to environmentally relevant doses of the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) across their lifespan experience accelerated reproductive senescence preceded by ovarian endocrine disruption. The purpose of this study was to determine the changes in ovarian gene expression that accompany the loss of ovarian function caused by chronic exposure to TCDD. Beginning in utero, female Sprague-Dawley rats received TCDD (1, 5, 50, or 200 ng/kg-week; n = 4 per group) or vehicle weekly throughout their lifespan, and were sacrificed on diestrus just prior to loss of reproductive cyclicity at 11 months of age. Microarray analysis was used to determine differences in ovarian gene expression between control and TCDD-treated (200 ng/kg-week) animals. To confirm microarray results, real-time PCR was used to assess changes in gene expression among treatment groups. TCDD treatment decreased (p < 0.05) proestrus serum estradiol concentrations with no effect on serum progesterone. In ovaries from rats treated with 200 ng/kg-week TCDD compared to controls, 19 genes of known function were found to be up-regulated, while 31 ovarian genes were found to be down-regulated ≥1.5-fold (p ≤ 0.05). Gene expression of 17α-hydroxylase decreased following chronic TCDD treatment, suggesting the decrease in estradiol biosynthesis may be a consequence of decreased substrate. Taken together with past studies indicating a lack of effect on hypothalamus or pituitary function, the apparent regulation of key ovarian genes support the hypothesis that chronic TCDD exposure directly affects ovarian function.
AB - The aryl hydrocarbon receptor (AHR) mediates the effects of many endocrine disruptors and contributes to the loss of fertility in polluted environments. Female rats exposed chronically to environmentally relevant doses of the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) across their lifespan experience accelerated reproductive senescence preceded by ovarian endocrine disruption. The purpose of this study was to determine the changes in ovarian gene expression that accompany the loss of ovarian function caused by chronic exposure to TCDD. Beginning in utero, female Sprague-Dawley rats received TCDD (1, 5, 50, or 200 ng/kg-week; n = 4 per group) or vehicle weekly throughout their lifespan, and were sacrificed on diestrus just prior to loss of reproductive cyclicity at 11 months of age. Microarray analysis was used to determine differences in ovarian gene expression between control and TCDD-treated (200 ng/kg-week) animals. To confirm microarray results, real-time PCR was used to assess changes in gene expression among treatment groups. TCDD treatment decreased (p < 0.05) proestrus serum estradiol concentrations with no effect on serum progesterone. In ovaries from rats treated with 200 ng/kg-week TCDD compared to controls, 19 genes of known function were found to be up-regulated, while 31 ovarian genes were found to be down-regulated ≥1.5-fold (p ≤ 0.05). Gene expression of 17α-hydroxylase decreased following chronic TCDD treatment, suggesting the decrease in estradiol biosynthesis may be a consequence of decreased substrate. Taken together with past studies indicating a lack of effect on hypothalamus or pituitary function, the apparent regulation of key ovarian genes support the hypothesis that chronic TCDD exposure directly affects ovarian function.
KW - Aryl hydrocarbon receptor
KW - Menopause
KW - Ovary
KW - Rat
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U2 - 10.1016/j.reprotox.2009.03.004
DO - 10.1016/j.reprotox.2009.03.004
M3 - Article
C2 - 19490992
AN - SCOPUS:67349131192
SN - 0890-6238
VL - 28
SP - 32
EP - 37
JO - Reproductive Toxicology
JF - Reproductive Toxicology
IS - 1
ER -