Rapid effects of pesticides on human granulosa-lutein cells

Y, Wu; Foster, Warren G.; Younglai, Edward V.

doi:10.1530/rep.1.00922

Cited by 9 publications

(10 citation statements)

References 60 publications

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“…The data are notable because methoxychlor is metabolized in the liver. Previous studies showed that methoxychlor induced [Ca 2+ ] i rises from extracellular space in human granulosa-lutein cells (38). In our study, methoxychlor appeared to increase [Ca 2+ ] i solely by inducing Ca 2+ entry from extracellular medium without involvement of Ca 2+ release from stores.…”

Section: Discussionsupporting

confidence: 63%

“…In vitro evidence shows that methoxychlor causes death or alters growth in several cell lines including murine Hepa-1c1c7 cells (18), human HepG2 cells (9), frog hepatocytes (32), fish hepatocytes (30), and chicken embryo hepatocytes (24). Although methoxychlor has been shown to induce intracellular Ca 2+ concentration ([Ca 2+ ] i ) rises in human granulosa-lutein cells (38) or human umbilical vein endothelial cells (40), the effect of methoxychlor on Ca 2+ signaling is unclear in hepatocytes from humans or animals. Thus the aim of this study was to explore the effect of methoxychlor on Ca 2+ movement and viability in human HA59T hepatoma cells.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Methoxychlor on Ca^(2+) Homeostasis and Apoptosis in HA59T Human Hepatoma Cells

et al. 2015

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Methoxychlor, an organochlorine pesticide, is thought to be an endocrine disrupter that affects Ca²⁺ homeostasis and cell viability in different cell models. This study explored the action of methoxychlor on cytosolic free Ca²⁺ concentrations ([Ca²⁺]i) and apoptosis in HA59T human hepatoma cells. Fura-2, a Ca²⁺-sensitive fluorescent dye, was applied to measure [Ca²⁺]i. Methoxychlor at concentrations of 0.1-1 μM caused a [Ca²⁺]i rise in a concentration-dependent manner. Removal of external Ca²⁺ abolished methoxychlor's effect. Methoxychlor-induced Ca²⁺ influx was confirmed by Mn²⁺-induced quench of fura-2 fluorescence. Methoxychlor-induced Ca²⁺ entry was inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators. Methoxychlor killed cells at concentrations of 10-130 μM in a concentration-dependent fashion. Chelation of cytosolic Ca²⁺ with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not prevent methoxychlor's cytotoxicity. Methoxychlor (10 and 50 μM) induced apoptosis concentration-dependently as determined by using Annexin V/propidium iodide staining. Together, in HA59T cells, methoxychlor induced a [Ca²⁺]i rise by inducing Ca²⁺ entry via protein kinase C-sensitive Ca²⁺-permeable channels, without causing Ca²⁺ release from stores. Methoxychlor also induced apoptosis that was independent of [Ca²⁺]i rises.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Effect of Methoxychlor on Ca^(2+) Homeostasis and Apoptosis in HA59T Human Hepatoma Cells

et al. 2015

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“…Therefore, it has been proposed that MXC may affect sex steroid levels by blocking a step in the steroid synthesis pathway that is downstream of generation of cAMP, but upstream of conversion of cholesterol to pregnenolone (Crellin et al 2001). The fact that MXC has also been shown to increase intracellular Ca 2C concentrations at low doses (w0.01-0.5 mg/ml; Wu et al 2006), suggests that MXC may interact with membrane receptors and parallel pathways that modulate ovarian steroidogenesis. In mouse antral follicles, MXC (1-100 mg/ml) was shown to decrease expression of mRNAs encoding the main steroidogenic enzymes with subsequent decreases in the main sex steroids .…”

Section: Chemicals That Alter the Availability Of Ovarian Hormonesmentioning

confidence: 99%

Endocrine-disrupting chemicals in ovarian function: effects on steroidogenesis, metabolism and nuclear receptor signaling

Craig¹,

Wang²,

Flaws³

2011

Reproduction

230

123

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Endocrine-disrupting chemicals (EDCs) are exogenous agents with the ability to interfere with processes regulated by endogenous hormones. One such process is female reproductive function. The major reproductive organ in the female is the ovary. Disruptions in ovarian processes by EDCs can lead to adverse outcomes such as anovulation, infertility, estrogen deficiency, and premature ovarian failure among others. This review summarizes the effects of EDCs on ovarian function by describing how they interfere with hormone signaling via two mechanisms: altering the availability of ovarian hormones, and altering binding and activity of the hormone at the receptor level. Among the chemicals covered are pesticides (e.g. dichlorodiphenyltrichloroethane and methoxychlor), plasticizers (e.g. bisphenol A and phthalates), dioxins, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons (e.g. benzo[a]pyrene).

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“…Therefore it is feasible that environmental toxicants can have agonist activities similar to those of progesterone, testosterone and estradiol as well as antagonist activities. Support for such a concept is seen in human granulosa-lutein cell data indicating that methoxychlor, o,p-DDE and kepone can act nongenomically in increasing intracellular calcium [237] and in a nonmammalian sperm system where o,p-DDT, methoxychlor, kepone and BPA inhibited progesterone action [238]. Moreover, many environmental estrogens can also act as anti-androgens [239], thereby emphasizing the relationship between structures and physiological functions.…”

Section: Nongenomic Effectsmentioning

confidence: 99%

Reproductive Toxicology of Environmental Toxicants: Emerging Issues and Concerns

Younglai

Wu²,

Foster

2007

CPD

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Environmental toxicants comprise a number of man-made organic chemicals which may resist metabolism or their metabolites may persist in the environment and accumulate in the food chain. Some of these persistent chemicals are carried over long distances via the atmospheric transport and can have biological effects in fish, wildlife and humans. In this review the relationship between structure of these chemicals, their mode of action and their possible roles in adverse developmental and reproductive processes in humans will be discussed. The focus will be on model polychlorinated biphenyls and dioxins, organochlorines, phthalates, a constituent of cigarette smoke (benzo-a-pyrene), synthetic polymers (polybrominated diphenyl ethers and polyfluorinated compounds), and a fungicide (vinclozolin).

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Rapid effects of pesticides on human granulosa-lutein cells

Abstract: Following our previous demonstration that p,p 0 -DDE (dichlorodiphenylchloroethylene), at environmentally relevant concen-

Cited by 9 publications

References 60 publications

Effect of Methoxychlor on Ca^(2+) Homeostasis and Apoptosis in HA59T Human Hepatoma Cells

Effect of Methoxychlor on Ca^(2+) Homeostasis and Apoptosis in HA59T Human Hepatoma Cells

Endocrine-disrupting chemicals in ovarian function: effects on steroidogenesis, metabolism and nuclear receptor signaling

Reproductive Toxicology of Environmental Toxicants: Emerging Issues and Concerns

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