Luderer Ulrike, Christensen Fletcher, Johnson Wesley O, She Jianwen, Ip Ho Sai Simon, Zhou Junqiang, Alvaran Josephine, Krieg Edward F, Kesner James S
Center for Occupational and Environmental Health and Division of Occupational and Environmental Medicine, Department of Medicine, University of California Irvine, 100 Theory, Suite 100, Irvine, CA 92617, USA; Dept of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697, USA; Program in Public Health, University of California Irvine, Irvine, CA 92697, USA.
Department of Statistics, University of California Irvine, Irvine, CA 92697, USA.
Environ Int. 2017 Mar;100:110-120. doi: 10.1016/j.envint.2016.12.021. Epub 2017 Jan 5.
Essentially all women are exposed to polycyclic aromatic hydrocarbons (PAHs), formed during incomplete combustion of organic materials, including fossil fuels, wood, foods, and tobacco. PAHs are ovarian toxicants in rodents, and cigarette smoking is associated with reproductive abnormalities in women. Biomonitoring of hydroxylated PAH (OH-PAH) metabolites in urine provides an integrated measure of exposure to PAHs via multiple routes and has been used to characterize exposure to PAHs in humans. We hypothesized that concentrations of OH-PAHs in urine are associated with reproductive function in women. We recruited women 18-44years old, living in Orange County, California to conduct daily measurement of urinary luteinizing hormone (LH) and estrone 3-glucuronide (E3G) using a microelectronic fertility monitor for multiple menstrual cycles; these data were used to calculate endocrine endpoints. Participants also collected urine samples on cycle day 10 for measurement of nine OH-PAHs. Models were constructed for eight endpoints using a Bayesian mixed modeling approach with subject-specific random effects allowing each participant to act as a baseline for her set of measurements. We observed associations between individual OH-PAH concentrations and follicular phase length, follicular phase LH and E3G concentrations, preovulatory LH surge concentrations, and periovulatory E3G slope and concentration. We have demonstrated the feasibility of using urinary reproductive hormone data obtained via fertility monitors to calculate endocrine endpoints for epidemiological studies of ovarian function during multiple menstrual cycles. The results show that environmental exposure to PAHs is associated with changes in endocrine markers of ovarian function in women in a PAH-specific manner.
基本上所有女性都会接触到多环芳烃（PAHs），这些物质在包括化石燃料、木材、食物和烟草在内的有机材料不完全燃烧过程中形成。PAHs是啮齿动物的卵巢毒物，吸烟与女性生殖异常有关。尿液中羟基化多环芳烃（OH-PAH）代谢物的生物监测提供了一种通过多种途径接触PAHs的综合测量方法，并已用于描述人类接触PAHs的情况。我们假设尿液中OH-PAHs的浓度与女性的生殖功能有关。我们招募了居住在加利福尼亚州奥兰治县、年龄在18至44岁之间的女性，使用微电子生育监测仪对多个月经周期的尿促黄体生成素（LH）和雌酮3-葡萄糖醛酸苷（E3G）进行每日测量；这些数据用于计算内分泌终点指标。参与者还在月经周期第10天收集尿液样本，以测量9种OH-PAHs。使用贝叶斯混合建模方法构建了8个终点指标的模型，该方法具有受试者特异性随机效应，允许每个参与者作为其一组测量值的基线。我们观察到个体OH-PAH浓度与卵泡期长度、卵泡期LH和E3G浓度、排卵前LH峰值浓度以及围排卵期E3G斜率和浓度之间存在关联。我们已经证明了使用通过生育监测仪获得的尿生殖激素数据来计算多个月经周期卵巢功能流行病学研究的内分泌终点指标的可行性。结果表明，环境中PAHs暴露以PAH特异性方式与女性卵巢功能的内分泌标志物变化有关。
