Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan.
Hum Reprod. 2010 Apr;25(4):986-94. doi: 10.1093/humrep/deq015. Epub 2010 Feb 10.
Phthalates are known to have estrogenic effects in cell models and experimental animals. However, the evidence regarding the effects of phthalates on human reproduction is still limited. We conducted a case-control study to determine whether estrogen-dependent diseases are associated with phthalate exposure and how the glutathione S-transferase M1 (GSTM1; a major detoxification enzyme) genotype modulates the risk.
We recruited subjects who underwent laparotomy and had pathologic confirmation of endometriosis (EN) (n = 28), adenomyosis (AD) (n = 16) and leiomyoma (LEI) (n = 36) from the Department of Obstetrics and Gynecology at a medical center in Taiwan between 2005 and 2007. Controls (n = 29) were patients without any of the three aforementioned gynecologic conditions. Urine samples were collected before surgery and analyzed for seven phthalate metabolites using liquid chromatography-tandem mass spectrometry. Peripheral lymphocytes were used for GSTM1 genotype determination.
Patients with LEIs had significantly higher levels of total urinary mono-ethylhexyl phthalate (SigmaMEHP; 52.1 versus 18.9 microg/g creatinine, P < 0.05) than the controls, whereas patients with EN had an increased level of urinary mono-n-butyl phthalate (94.1 versus 58.0 microg/g creatinine, P < 0.05). Subjects with GSTM1 null genotype had significantly increased odds for AD relative to those with GSTM1 wild genotype [odds ratio (OR) = 5.30; 95% CI, 1.22-23.1], even after adjustment for age and phthalate exposure. Subjects who carried the GSTM1 null genotype and had a high urinary level of SigmaMEHP showed a significantly increased risk for AD (OR = 10.4; 95% CI, 1.26-85.0) and LEIs (OR = 5.93; 95% CI, 1.10-31.9) after adjustment for age, compared with those with GSTM1 wild-type and low urinary level of SigmaMEHP.
These results suggest that both GSTM1 null and phthalate exposure are associated with AD and LEI. Larger studies are warranted to investigate potential interaction between GSTM1 null and phthalate exposure in the etiology of estrogen-dependent gynecologic conditions.
邻苯二甲酸酯在细胞模型和实验动物中具有雌激素效应。然而，关于邻苯二甲酸酯对人类生殖的影响的证据仍然有限。我们进行了一项病例对照研究，以确定雌激素依赖性疾病是否与邻苯二甲酸酯暴露有关，以及谷胱甘肽 S-转移酶 M1（GSTM1；一种主要的解毒酶）基因型如何调节风险。
我们招募了 2005 年至 2007 年期间在台湾一家医疗中心妇产科接受腹腔镜检查并经病理证实患有子宫内膜异位症（EN）（n = 28）、子宫腺肌病（AD）（n = 16）和子宫肌瘤（LEI）（n = 36）的患者。对照组（n = 29）为无上述三种妇科疾病的患者。手术前采集尿液样本，采用液相色谱-串联质谱法分析七种邻苯二甲酸代谢物。使用外周血淋巴细胞进行 GSTM1 基因型测定。
与对照组相比，患有 LEI 的患者尿液中单乙基己基邻苯二甲酸（SigmaMEHP）总浓度明显升高（52.1 与 18.9μg/g 肌酐，P<0.05），而患有 EN 的患者尿液中单正丁基邻苯二甲酸浓度升高（94.1 与 58.0μg/g 肌酐，P<0.05）。与 GSTM1 野生型相比，GSTM1 缺失基因型的 AD 患者发生的可能性显著增加[比值比（OR）=5.30；95%置信区间（CI），1.22-23.1]，即使在校正年龄和邻苯二甲酸暴露后也是如此。携带 GSTM1 缺失基因型且 SigmaMEHP 尿液水平较高的患者发生 AD（OR=10.4；95%CI，1.26-85.0）和 LEI（OR=5.93；95%CI，1.10-31.9）的风险显著增加，与 GSTM1 野生型且 SigmaMEHP 尿液水平较低的患者相比。
这些结果表明，GSTM1 缺失和邻苯二甲酸酯暴露均与 AD 和 LEI 相关。需要进行更大规模的研究来探讨 GSTM1 缺失与邻苯二甲酸酯暴露在雌激素依赖性妇科疾病发病机制中的潜在相互作用。
