Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; Biomedical Research Center (CIBM), University of Granada, 18100 Granada, Spain.
Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain.
Sci Total Environ. 2021 May 15;769:144563. doi: 10.1016/j.scitotenv.2020.144563. Epub 2021 Jan 17.
To examine the association between urinary metabolites of organophosphate (OP) pesticides and serum concentrations of thyroid and reproductive hormones in male adolescents and to assess the potential effect of interactions between OP pesticides and paraoxonase 1 (PON1) polymorphisms on hormone levels.
Study subjects (N = 117) were male 16- to 17-year-olds from the Environment and Childhood (INMA)-Granada cohort in Spain. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos/chlorpyrifos-methyl, 2-isopropyl-6-methyl-4-pyrimidinol (IMPy), a metabolite of diazinon, and diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP), non-specific metabolites of OP pesticides, were measured in a spot urine sample from each subject and adjusted for creatinine. Levels of reproductive hormones (total testosterone [TT], estradiol [E], dehydroepiandrosterone sulfate [DHEAS], sex hormone binding globulin [SHBG], luteinizing hormone [LH], follicle stimulating hormone [FSH], anti-Müllerian hormone [AMH], insulin growth factor 1 [IGF-1], and prolactin), thyroid hormones (free thyroxine [FT4], total triiodothyronine [TT3], and thyroid stimulating hormone [TSH]), and PON1 Q192R and L55M polymorphisms were determined in blood drawn during the same clinical visit.
Multiple linear regression models showed that detectable levels of TCPy were associated with an increase in DHEAS and decreases in E, FSH, and AMH; detectable IMPy with increases in E, DHEAS, FSH, AMH, and prolactin and decreases in SHBG and LH; and detectable DETP with marginally-significant increases in TT and TT3 and decreases in FSH, AMH, and prolactin. The effect of IMPy and DETP on DHEAS and TT levels, respectively, was higher in subjects that carried the PON1 55MM genotype, while the effect of TCPy, IMPy, and DETP on thyroid hormone levels was higher in PON1 192QR/RR or 55MM genotype carriers.
In male adolescents, non-occupational exposure to OP pesticides was associated with several changes in reproductive and thyroid hormone levels, and the magnitude of some associations was greater in adolescents genetically more susceptible to OP pesticide exposure who carry the PON1 55MM genotype.
研究有机磷 (OP) 农药尿代谢物与男性青少年血清甲状腺和生殖激素浓度之间的关系，并评估 OP 农药与对氧磷酶 1 (PON1) 多态性之间的相互作用对激素水平的潜在影响。
研究对象为西班牙格拉纳达环境与儿童 (INMA) 队列中的 117 名 16 至 17 岁的男性青少年。在每个研究对象的一份随机尿液样本中测量了 3,5,6-三氯-2-吡啶醇 (TCPy)（毒死蜱/毒死蜱甲基的代谢物）、2-异丙基-6-甲基-4-嘧啶醇 (IMPy)（二嗪磷的代谢物）和二乙基硫代磷酸酯 (DETP) 和二乙基二硫代磷酸酯 (DEDTP)，这是 OP 农药的非特异性代谢物，经过肌酐调整。生殖激素（总睾酮 [TT]、雌二醇 [E]、脱氢表雄酮硫酸酯 [DHEAS]、性激素结合球蛋白 [SHBG]、黄体生成素 [LH]、卵泡刺激素 [FSH]、抗苗勒管激素 [AMH]、胰岛素生长因子 1 [IGF-1] 和催乳素）、甲状腺激素（游离甲状腺素 [FT4]、总三碘甲状腺原氨酸 [TT3] 和促甲状腺激素 [TSH]）和 PON1 Q192R 和 L55M 多态性在同一临床就诊时抽取的血液中进行测定。
多元线性回归模型显示，可检测到的 TCPy 水平与 DHEAS 升高和 E、FSH 和 AMH 降低有关；可检测到的 IMPy 与 E、DHEAS、FSH、AMH 和催乳素升高以及 SHBG 和 LH 降低有关；可检测到的 DETP 与 TT 和 TT3 略有升高以及 FSH、AMH 和催乳素降低有关。PON1 55MM 基因型个体中，IMPy 和 DETP 对 DHEAS 和 TT 水平的影响更高，而 TCPy、IMPy 和 DETP 对甲状腺激素水平的影响在 PON1 192QR/RR 或 55MM 基因型携带者中更高。
在男性青少年中，非职业性接触 OP 农药与生殖和甲状腺激素水平的多项变化有关，PON1 55MM 基因型遗传易感性较高的青少年中，一些关联的程度更大。
