Effect of dioxin on ovarian function in the cynomolgus macaque (M. fascicularis)

Moran, Francisco; Tarara, Ross P.; Chen, J.; Santos, S. S. D.; Cheney, Adrienne; Overstreet, James W.; Lasley, Bill L.

doi:10.1016/s0890-6238(01)00138-1

Cited by 22 publications

(17 citation statements)

References 19 publications

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“…This report provides the basis for a partial explanation of the failure of urinary E 1 C metabolites of ovarian estrogen production to decline in parallel with the expected decline in ovarian function, as reported earlier by Gilardi et al [1997], Moran et al [2001], and Shideler et al [2001]. None of these studies showed a statistically significant decline in detected urinary E 1 C, despite clear decreases in all other aspects of ovarian function.…”

Section: Discussionsupporting

confidence: 70%

Contribution of ovarian steroid production to urinary estrone conjugate concentrations in Macaca mulatta

Shideler

Gee

Chen

et al. 2003

American J Primatol

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This study was designed to test the hypothesis that basal estrone conjugate (E1C) profiles do not accurately detect ovarian function when ovarian estrogen production is low or absent. We employed surgical removal of active ovaries from laboratory rhesus macaques to simulate an acute decline in ovarian estrogen production. In the first experiment, urine samples collected prior to and following ovariectomy (Ovx) were subjected to high-performance liquid chromatography (HPLC) separation. Eluates were then assayed for E1C immunoreactive components. The results indicated a modest decrease in total immunoreactive polar conjugates following ovariectomy, with no substantial change in the overall retention profile. In the second experiment, estradiol (E2) cypionate injections were used to replace the E2 component of ovarian estrogen production in the treated (Tx) group, while the control group (C) received only vehicle. Urine samples were hydrolyzed and individual estrogens were separated by celite chromatography prior to immuno-assay. Both the Tx and C groups exhibited similar urinary excretion levels of estrone (E1), E2, and E1C prior to Ovx (Pre-Ovx) and after Ovx (Post-Ovx), but there were significant differences between groups after treatment (Post-Tx). Significant differences were observed in the Tx group's excretion of E1, E2, and E1C in the Pre- vs. Post-Ovx samples and in the Post-Ovx and Post-Tx samples. The C group also showed the expected significant differences in the Pre- vs. Post-Ovx samples, as well as in the Pre-Ovx and Post-Tx samples. The results indicate that the use of E1C measurements is clearly a suitable method for monitoring ovarian function in intact, cycling animals, but urinary E2 measurements are required to verify loss of follicular activity.

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Section: Discussionsupporting

confidence: 70%

Contribution of ovarian steroid production to urinary estrone conjugate concentrations in Macaca mulatta

Shideler

Gee

Chen

et al. 2003

American J Primatol

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“…However, the reproductive consequences of TCDD exposure appear to be highly dependent on species and gender as well as on dose, duration, and time after exposure (6,12,(22)(23)(24)(25). Therefore, the selection of the experimental model and design plays an important role in the ability to extrapolate results in this area of research.…”

Section: Discussionmentioning

confidence: 99%

“…TCDD apparently decreases estrogen production from porcine granulosa cells in vitro and progesterone from porcine luteal cells (33). In the nonhuman primate, TCDD induces abortion and decreases estrogen secretion by targeting both the trophoblast and the ovary (3)(4)(5)(6). In contrast, comparatively little is known about specific molecular targets of TCDD or its effects on human reproduction.…”

Section: Discussionmentioning

confidence: 99%

“…A single dose of TCDD induces abortion and is accompanied by a decrease in serum estradiol (E2) in the laboratory macaque (3)(4)(5). This acute response is followed by chronic arrest of follicular growth, characterized by anovulation and decreased ovarian steroidogenesis (6). The dangers associated with human TCDD exposure are exacerbated by its extremely long half-life in the body (7,8).…”

Section: 378-tetrachlorodibenzo-p-dioxin (Tcdd) Ismentioning

confidence: 99%

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Molecular Target of Endocrine Disruption in Human Luteinizing Granulosa Cells by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin: Inhibition of Estradiol Secretion Due to Decreased 17α-Hydroxylase/17,20-Lyase Cytochrome P450 Expression

et al. 2003

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Estradiol (E2) production by human luteinized granulosa cells (hLGC) is inhibited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The molecular target of TCDD toxicity has not been identified. The decrease in E2 is ameliorated by androgen substrate addition and is not associated with changes in aromatase cytochrome P450 (P450arom) activity or protein expression. An antihuman 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17) antisera and a direct radiometric assay of 17,20-lyase activity were used to test the hypothesis that TCDD targets P450c17, thereby decreasing substrate availability for E2 synthesis by hLGC. P450c17 expression and 17,20-lyase activity were detected in hLGC with high levels of E2 secretion. Western immunoblot analysis demonstrated that TCDD treatment of hLGC decreased the expression of P450c17 by as much 50% (P < 0.05). TCDD exposure induced a 65% decrease in 17,20-lyase activity (P < 0.05), but no changes were seen in P450arom or in nicotinamide adenine dinucleotide phosphate (reduced)-cytochrome P450 oxidoreductase (reductase). Furthermore, the decreases in P450c17 and 17,20-lyase were proportional to the inhibition of E2 secretion. We conclude that the molecular target for endocrine disruption of hLGC by TCDD is P450c17, specifically decreasing the supply of androgens for E2 synthesis, and that it does not involve either P450arom or the redox partner protein reductase.

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“…Studies in rats and monkeys suggest that TCDD may affect ovarian function directly or indirectly via the pituitary (Gao et al 2000; Li et al 1995a; Moran et al 2001). In utero and lactational TCDD exposure in rats has been associated with reduced ovarian weight and decreased number of corpus lutea and pre-antral and antral follicles (Heimler et al 1998).…”

mentioning

confidence: 99%

Serum Dioxin Concentrations and Age at Menopause

Eskenazi

Warner

Marks

et al. 2005

Environ Health Perspect

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2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), a halogenated compound that binds the aryl hydrocarbon receptor, is a by-product of numerous industrial processes including waste incineration. Studies in rats and monkeys suggest that TCDD may affect ovarian function. We examined the relationship of TCDD and age at menopause in a population of women residing near Seveso, Italy, in 1976, at the time of a chemical plant explosion. We included 616 of the women who participated 20 years later in the Seveso Women’s Health Study. All women were premenopausal at the time of the explosion, had TCDD levels measured in serum collected soon after the explosion, and were ≥ 35 years of age at interview. Using proportional hazards modeling, we found a 6% nonsignificant increase in risk of early menopause with a 10-fold increase in serum TCDD. When TCDD levels were categorized, compared with women in the lowest quintile (< 20.4 ppt), women in quintile 2 (20.4–34.2 ppt) had a hazard ratio (HR) of 1.1 (p = 0.77), quintile 3 (34.3–54.1 ppt) had an HR of 1.4 (p = 0.14), quintile 4 (54.2–118 ppt) had an HR of 1.6 (p = 0.10), and quintile 5 (> 118 ppt) had an HR of 1.1 (p = 0.82) for risk of earlier menopause. The trend toward earlier menopause across the first four quintiles is statistically significant (p = 0.04). These results suggest a nonmonotonic dose-related association with increasing risk of earlier menopause up to about 100 ppt TCDD, but not above.

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Effect of dioxin on ovarian function in the cynomolgus macaque (M. fascicularis)

Cited by 22 publications

References 19 publications

Contribution of ovarian steroid production to urinary estrone conjugate concentrations in Macaca mulatta

Contribution of ovarian steroid production to urinary estrone conjugate concentrations in Macaca mulatta

Molecular Target of Endocrine Disruption in Human Luteinizing Granulosa Cells by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin: Inhibition of Estradiol Secretion Due to Decreased 17α-Hydroxylase/17,20-Lyase Cytochrome P450 Expression

Serum Dioxin Concentrations and Age at Menopause

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