Sánchez-Peña L C, Reyes B E, López-Carrillo L, Recio R, Morán-Martínez J, Cebrián M E, Quintanilla-Vega B
Sección de Toxicología, CINVESTAV-IPN, 2508, Mexico City, 07360, Mexico.
Toxicol Appl Pharmacol. 2004 Apr 1;196(1):108-13. doi: 10.1016/j.taap.2003.11.023.
Our objective was to evaluate alterations in sperm chromatin structure in men occupationally exposed to a mixture of organophosphorus pesticides (OP) because these alterations have been proposed to compromise male fertility and offspring development. Chromatin susceptibility to in situ acid-induced denaturation structure was assessed by the sperm chromatin structure assay (SCSA). Urinary levels of alkylphosphates (DAP) were used to assess exposure. Diethylthiophosphate (DETP) was the most frequent OP metabolite found in urine samples indicating that compounds derived from thiophosphoric acid were mainly used. Chromatin structure was altered in most samples. About 75% of semen samples were classified as having poor fertility potential (>30% of Percentage of DNA Fragmentation Index [DFI%]), whereas individuals without OP occupational exposure showed average DFI% values of 9.9%. Most parameters of conventional semen analysis were within normality except for the presence of immature cells (IGC) in which 82% of the samples were above reference values. There were significant direct associations between urinary DETP concentrations and mean DFI and SD-DFI but marginally (P = 0.079) with DFI%, after adjustment for potential confounders, including IGC. This suggests that OP exposure alters sperm chromatin condensation, which could be reflected in an increased number of cells with greater susceptibility to DNA denaturation. This study showed that human sperm chromatin is a sensitive target to OP exposure and may contribute to adverse reproductive outcomes. Further studies on the relevance of protein phosphorylation as a possible mechanism by which OP alter sperm chromatin are required.
我们的目标是评估职业性接触有机磷农药（OP）混合物的男性精子染色质结构的改变，因为有人提出这些改变会损害男性生育能力和后代发育。通过精子染色质结构分析（SCSA）评估染色质对原位酸诱导变性结构的敏感性。使用尿中烷基磷酸盐（DAP）水平评估暴露情况。二乙硫代磷酸酯（DETP）是尿样中最常见的OP代谢物，表明主要使用了硫代磷酸衍生的化合物。大多数样本的染色质结构发生了改变。约75%的精液样本被归类为生育潜力差（DNA碎片化指数百分比[DFI%]>30%），而无OP职业暴露的个体DFI%平均值为9.9%。除了存在未成熟细胞（IGC）外，传统精液分析的大多数参数均在正常范围内，其中82%的样本高于参考值。在调整包括IGC在内的潜在混杂因素后，尿中DETP浓度与平均DFI和SD-DFI之间存在显著的直接关联，但与DFI%的关联微弱（P = 0.079）。这表明OP暴露会改变精子染色质凝聚，这可能反映在对DNA变性更敏感的细胞数量增加上。本研究表明，人类精子染色质是OP暴露的敏感靶点，可能导致不良生殖结局。需要进一步研究蛋白质磷酸化作为OP改变精子染色质的可能机制的相关性。
