RESUMO
Objective: This study aimed to compare 9 perfluoroalkyl sulfonic acids (PFSA) with carbon chain lengths (C4-C12) to inhibit human placental 3ß-hydroxysteroid dehydrogenase 1 (3ß-HSD1), aromatase, and rat 3ß-HSD4 activities. Methods: Human and rat placental 3ß-HSDs activities were determined by converting pregnenolone to progesterone and progesterone secretion in JEG-3 cells was determined using HPLC/MS-MS, and human aromatase activity was determined by radioimmunoassay. Results: PFSA inhibited human 3ß-HSD1 structure-dependently in the order: perfluorooctanesulfonic acid (PFOS, half-maximum inhibitory concentration, IC 50: 9.03 ± 4.83 µmol/L) > perfluorodecanesulfonic acid (PFDS, 42.52 ± 8.99 µmol/L) > perfluoroheptanesulfonic acid (PFHpS, 112.6 ± 29.39 µmol/L) > perfluorobutanesulfonic acid (PFBS) = perfluoropentanesulfonic acid (PFPS) = perfluorohexanesulfonic acid (PFHxS) = perfluorododecanesulfonic acid (PFDoS) (ineffective at 100 µmol/L). 6:2FTS (1H, 1H, 2H, 2H-perfluorooctanesulfonic acid) and 8:2FTS (1H, 1H, 2H, 2H-perfluorodecanesulfonic acid) did not inhibit human 3ß-HSD1. PFOS and PFHpS are mixed inhibitors, whereas PFDS is a competitive inhibitor. Moreover, 1-10 µmol/L PFOS and PFDS significantly reduced progesterone biosynthesis in JEG-3 cells. Docking analysis revealed that PFSA binds to the steroid-binding site of human 3ß-HSD1 in a carbon chain length-dependent manner. All 100 µmol/L PFSA solutions did not affect rat 3ß-HSD4 and human placental aromatase activity. Conclusion: Carbon chain length determines inhibitory potency of PFSA on human placental 3ß-HSD1 in a V-shaped transition at PFOS (C8), with inhibitory potency of PFOS > PFDS > PFHpS > PFBS = PFPS = PFHxS = PFDoS = 6:2FTS = 8:2FTS.
Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Humanos , Gravidez , Feminino , Ratos , Animais , Placenta , Progesterona/metabolismo , Progesterona/farmacologia , Aromatase/metabolismo , Aromatase/farmacologia , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Hidroxiesteroide Desidrogenases/metabolismo , Hidroxiesteroide Desidrogenases/farmacologiaRESUMO
Glutathione S-transferase T1 (GSTT1) null genotype has been indicated to be correlated with preterm delivery (PTD) susceptibility, but study results were still debatable. Thus, a meta-analysis was conducted. PubMed, EMBASE, and CNKI were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association in the random-effects model or fixed-effects model. Nine case-control studies with a total of 2526 cases and 4565 controls were eligible. The null genotype of GSTT1 was associated with a significantly increased risk of PTD when compared with present genotype (OR = 1.18; 95% CI 1.05-1.33; I(2) = 33). In the subgroup analysis according to ethnicity, significantly increased PTD risk was observed in Asians (OR = 1.20; 95% CI 1.01-1.33; I(2) = 0%) but not in Caucasians (OR = 1.32; 95% CI 0.89-1.97; I(2) = 77). This meta-analysis suggested that GSTT1 null genotype may be associated with the risk of PTD.