The use of a unique co-culture model of fetoplacental steroidogenesis as a screening tool for endocrine disruptors: The effects of neonicotinoids on aromatase activity and hormone production

Autor: Andrée-Anne Hudon-Thibeault, Élyse Caron-Beaudoin, J. Thomas Sanderson, Cathy Vaillancourt, Rachel Viau
Přispěvatelé: Center for Interdisciplinary Research on Well-Being, Health, Society and Environment (CINBIOSE), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Université du Québec à Montréal = University of Québec in Montréal (UQAM)
Rok vydání: 2017
Předmět:
0301 basic medicine
Insecticides
Pyridines
[SDV]Life Sciences [q-bio]
Placenta
Thiazines
Endocrine Disruptors
010501 environmental sciences
Toxicology
01 natural sciences
Neonicotinoids
chemistry.chemical_compound
Pregnancy
Fetoplacental unit
Adrenocortical Carcinoma
Cytochrome P-450 CYP3A
Choriocarcinoma
Aromatase
reproductive and urinary physiology
Estradiol
Imidazoles
Nitro Compounds
Thiacloprid
medicine.anatomical_structure
Uterine Neoplasms
Female
Thiamethoxam
hormones
hormone substitutes
and hormone antagonists
Steroid 16α-hydroxylase (CYP3A7)
medicine.medical_specialty
Estrone
medicine.drug_class
Biology
03 medical and health sciences
Cell Line
Tumor
Internal medicine
Oxazines
medicine
Humans
0105 earth and related environmental sciences
Pharmacology
Nonicotinoids
Estriol
Estrogens
Androgen
Coculture Techniques
Thiazoles
030104 developmental biology
Endocrinology
Gene Expression Regulation
chemistry
Estrogen
biology.protein
Co-culture
Hormone
Zdroj: Toxicology and Applied Pharmacology
Toxicology and Applied Pharmacology, Elsevier, 2017, 332, pp.15-24. ⟨10.1016/j.taap.2017.07.018⟩
ISSN: 0041-008X
1096-0333
DOI: 10.1016/j.taap.2017.07.018
Popis: International audience; Estrogen biosynthesis during pregnancy is dependent on the collaboration between the fetus producing the androgen precursors, and the placenta expressing the enzyme aromatase (CYP19). Disruption of estrogen production by contaminants may result in serious pregnancy outcomes. We used our recently developed in vitro co-culture model of fetoplacental steroidogenesis to screen the effects of three neonicotinoid insecticides on the catalytic activity of aromatase and the production of steroid hormones. A co-culture of H295R human adrenocortical carcinoma cells with fetal characteristics and BeWo human choriocarcinoma cells which display characteristics of the villous cytotrophoblast was exposed for 24h to various concentrations of three neonicotinoids: thiacloprid, thiamethoxam and imidacloprid. Aromatase catalytic activity was determined in both cell lines using the tritiated water-release assay. Hormone production was measured by ELISA. The three neonicotinoids induced aromatase activity in our fetoplacental co-culture and concordingly, estradiol and estrone production were increased. In contrast, estriol production was strongly inhibited by the neonicotinoids. All three pesticides induced the expression of CYP3A7 in H295R cells, and this induction was reversed by co-treatment of H295R cells with exogenous estriol. CYP3A7 is normally expressed in fetal liver and is a key enzyme involved in estriol synthesis. We suggest that neonicotinoids are metabolized by CYP3A7, thus impeding the 16α-hydroxylation of fetal DHEA(-sulfate), which is normally converted to estriol by placental aromatase. We successfully used the fetoplacental co-culture as a physiologically relevant tool to highlight the potential effects of neonicotinoids on estrogen production, aromatase activity and CYP3A7 expression during pregnancy.
Databáze: OpenAIRE
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