Modulation of aromatase activity and mRNA by various selected pesticides in the human choriocarcinoma JEG-3 cell line

Laville, Nathalie; Balaguer, Patrick; Brion, François; Hinfray, Nathalie; Casellas, Claude; Porcher, Jean‐Marc; Aı̈t-Aı̈ssa, Sélim

doi:10.1016/j.tox.2006.08.021

Cited by 101 publications

(58 citation statements)

References 41 publications

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“…These findings could be related to alterations in estradiol levels, since this hormone plays a critical role in the maintenance of primate pregnancy (Albrecht et al, 2000), with its synthesis depending on ArM activity. In contrast, the OCs aldrin, chlordane, endosulfan and methoxychlor were reported to induce ArM activity in JEG-3 cells (Laville et al, 2006). Considering that an increased level of estradiol in the syncytiotrophoblast may have an impact on testicular descent (Had˘ziselimović et al, 2000), and that an association of congenital cryptorchidism with trans-chlordane levels in breast milk has been reported (Damgaard et al, 2006), it now remains to be determined if the increasing incidence of this reproductive abnormality is associated with trans-chlordane induced up regulation of placental ArM.…”

Section: Effects On Aromatasementioning

confidence: 99%

“…Since regulation of ArM expression in these cells is the same as in the placenta, JEG-3 cells have been proposed to be a valuable tool for the assessment of potential steroidogenesis disruption. ArM activity was found to decrease by incubation with the OCs lindane ( HCH) and heptachlor (Laville et al, 2006), with a significant association between HCH levels in female blood and recurrent miscarriages also being reported (Pathak et al, 2010). These findings could be related to alterations in estradiol levels, since this hormone plays a critical role in the maintenance of primate pregnancy (Albrecht et al, 2000), with its synthesis depending on ArM activity.…”

Section: Effects On Aromatasementioning

confidence: 99%

See 1 more Smart Citation

Placental Toxicology of Pesticides

Magnarelli¹,

Guiñazú²

2012

Recent Advances in Research on the Human Placenta

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Section: Effects On Aromatasementioning

confidence: 99%

Section: Effects On Aromatasementioning

confidence: 99%

Placental Toxicology of Pesticides

Magnarelli¹,

Guiñazú²

2012

Recent Advances in Research on the Human Placenta

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“…In a previous study, we have reported that several currently used pesticides were able to interfere with steroid hormone biosynthesis by altering aromatase enzymatic activity and gene expression in a human placental cell line (Laville et al, 2006). In order to gain further information on their ED potency, these compounds (listed in Table 1) were tested in the present study for their ability to alter the transcriptional activity of the androgen receptor (AR) in the MDA-kb2 reporter cell line (Wilson et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Anti-androgenic activities of environmental pesticides in the MDA-kb2 reporter cell line

Aı̈t-Aı̈ssa¹,

Laskowski²,

Laville³

et al. 2010

Toxicology in Vitro

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Pesticides have been suspected to act as endocrine disruptive compounds (EDCs) through several mechanisms of action, however data are still needed for a number of currently used pesticides. In the present study, 30 environmental pesticides selected from different chemical classes (azole, carbamate, dicarboximide, oganochlorine, organophosphorus, oxadiazole, phenylureas, pyrazole, pyrimidine, pyrethroid and sulfonylureas) were tested for their ability to alter in vitro the transcriptional activity of the androgen receptor in the MDA-kb2 reporter cell line. The responsiveness of the system was checked by using a panel of reference ligands of androgen and glucocorticoid receptors. When tested alone at concentrations up to 10 µM, none of the studied pesticides were able to induce the reporter gene after a 18 hour exposure.Conversely, co-exposure experiments with 0.1 nM dihydrotestosterone (DHT) allowed identifying 15 active pesticides with IC 50 ranging from 0.2 µM for vinclozolin to 12 µM for fenarimol. Fipronil and bupirimate were here newly described for their AR antagonistic activity.

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“…Particularly the aromatase (Cyp19) enzyme has been found as a target for many pesticides, some pesticides inducing the activity and others inhibiting it (Sanderson et al, 2002;Vinggaard et al, 2000;Zarn et al, 2003). Propiconazole and other azole fungicides have been shown to inhibit aromatase activity (Kjeldsen et al, 2013), whereas cypermethrin and triazine herbicides have been reported to induce the activity in vitro (Laville et al, 2006;Sanderson et al, 2001;Trosken et al, 2006;Zarn et al, 2003). As the observed effects in vivo were only seen for Mix 5, it suggests that one or both pesticides specific for Mix 5, terbuthylazine and/or malathion are driving the effect.…”

Section: Discussionmentioning

confidence: 99%

In vitro–in vivo correlations for endocrine activity of a mixture of 5 currently used pesticides

et al. 2013

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Two pesticide mixtures were investigated for potential endocrine activity. Mix 3 consisted of bitertanol, propiconazole, and cypermethrin, and Mix 5 included malathion and terbuthylazine in addition to the three pesticides in Mix 3. All five single pesticides and the two mixtures were investigated for their ability to affect steroidogenesis in vitro in H295R cells. The pesticides alone and both mixtures affected steroidogenesis with both mixtures causing increase in progesterone and decrease in testosterone. For Mix 5 an increase in estradiol was seen as well, indicating increased aromatase activity. The two mixtures were also investigated in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses. Decreased estradiol and reduced placental testosterone were seen in dams exposed to Mix 5. Also a significant increase in aromatase mRNA-levels in female adrenal glands was found for Mix5. However, either of the two mixtures showed any effects on fetal hormone levels in plasma or testis, or on anogenital distance. Overall, potential aromatase induction was found for Mix 5 both in vitro and in vivo, but not for Mix 3, an effect likely owed to terbuthylazine in Mix 5. However, the hormonal responses in vitro were only partly reflected in vivo, probably due to some toxicokinetic issues, as the pesticide levels in the amniotic fluid also were found to be negatively affected by the number of compounds present in the mixtures. Nonetheless, the H295R assay gives hints on conceivable interference with steroidogenesis, thus generating hypotheses on in vivo effects.

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Modulation of aromatase activity and mRNA by various selected pesticides in the human choriocarcinoma JEG-3 cell line

Cited by 101 publications

References 41 publications

Placental Toxicology of Pesticides

Placental Toxicology of Pesticides

Anti-androgenic activities of environmental pesticides in the MDA-kb2 reporter cell line

In vitro–in vivo correlations for endocrine activity of a mixture of 5 currently used pesticides

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