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Toxicol Mech Methods ; 30(5): 336-349, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32166990

RESUMO

In cosmetics and food products, parabens are widely used as antimicrobial agents. Reports have suggested that parabens may be linked to infertility, owing to their effects on basal steroidogenesis properties or their capacity to inflict mitochondrial damage. Despite growing concerns about parabens as endocrine disruptors, it is unclear whether they affect any of these actions in humans, particularly at environmentally relevant concentrations. In this work, an in vitro primary culture of human granulosa cells was used to evaluate steroidogenesis, based on the assessment of progesterone production and regulation of critical steroidogenic genes: CYP11A1, HSD3B1, CYP19A1, and HSD17B1. The effects of two commercially relevant parabens, methylparaben (MPB) and butylparaben (BPB), were screened. Cells were exposed to multiple concentrations ranging from relatively low (typical environmental exposure) to relatively high. The effect was assessed by the parabens' ability to modify steroidogenic genes, progesterone or estradiol production, and on mitochondrial health, by evaluating mitochondrial activity as well as mtDNA content. Neither MPB nor BPB showed any effect over progesterone production or the expression of genes controlling steroid production. Only BPB affected the mitochondria, decreasing mtDNA content at supraphysiological concentrations (1000 nM). Prolonged exposure to these compounds produced no effects in neither of these parameters. In conclusion, neither MPB nor BPB significantly affected basal steroidogenesis in granulosa cells. Although evidence supporting paraben toxicity is prevalent, here we put forth evidence that suggests that parabens do not affect basal steroidogenesis in human granulosa cells.


Assuntos
Disruptores Endócrinos/toxicidade , Células da Granulosa/efeitos dos fármacos , Parabenos/toxicidade , Progesterona/biossíntese , Adulto , Aromatase/genética , Líquidos Corporais/química , Células Cultivadas , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , DNA Mitocondrial/metabolismo , Relação Dose-Resposta a Droga , Disruptores Endócrinos/administração & dosagem , Disruptores Endócrinos/análise , Estradiol Desidrogenases/genética , Feminino , Células da Granulosa/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Complexos Multienzimáticos/genética , Parabenos/administração & dosagem , Parabenos/análise , Cultura Primária de Células , Progesterona Redutase/genética , Esteroide Isomerases/genética
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