Phthalate exposure, even below US EPA reference doses, was associated with semen quality and reproductive hormones: Prospective MARHCS study in general population
Phthalate exposure, even below US EPA reference doses, was associated with semen quality and reproductive hormones: Prospective MARHCS study in general population
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邻苯二甲酸盐暴露，即使低于美国 EPA 参考剂量，也与精液质量和生殖激素相关：一般人群的前瞻性 MARHCS 研究
DOI：
10.1016/j.envint.2017.04.005
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发表时间：
2017-07-01
影响因子：
11.8
通讯作者：
Cao, Jia
中科院分区：
文献类型：
--
作者：
Chen, Qing;Yang, Huan;Cao, Jia
背景：环境保护局邻苯二甲酸盐摄入量的参考剂量(EPA RFDS)是基于有限的证据，特别是关于低剂量的男性生殖毒性。这项研究调查了一般人群中邻苯二甲酸盐暴露与精液参数和生殖激素之间的关系，与EPA RfD相比，邻苯二甲酸盐暴露较低。方法：MARHCS(Male-Reproductive-Health-in-Chongqing-College-Students)队列招募了796名经历过校园搬迁和环境暴露转移的男性学生。调查搬迁前后尿液、精液和血液中13种邻苯二甲酸盐代谢产物与11种精液/激素结果(包括精液量、精子密度、总精子数、进行性活动率、形态正常等5项精液参数)和6种血清生殖激素(包括雌二醇、卵泡刺激素、黄体生成素、催乳素、孕酮、睾酮)之间的关系；(2)重新分析估计邻苯二甲酸盐摄入量低于RFDS的受试者的代谢产物-结果相关性；(3)搬迁后邻苯二甲酸盐代谢产物的变化和精液/激素结果的变化；(4)这些变化之间的联系。结果：(1)除两种外，所有精液/激素结果都与至少一种邻苯二甲酸酯代谢物有关，例如，每四分位数的邻苯二甲酸单乙酯分别导致精子密度、精子总数和前进活动率分别下降5.3%、5.7%和2.6%。(2)在邻苯二甲酸盐摄入量低于RFDS的受试者中，这些代谢物与结果的相关性仍然显著。(3)搬迁后，除邻苯二甲酸单(2-乙基己基)酯外，其余代谢物均下降(P<；0.001)；同时，精液量、正常形态、雌二醇和黄体生成素增加(分别增加5.9%、25.0%、34.2%和10.0%)，睾酮减少(减少7.0%)。(4)搬迁后精液量、正常形态、雌二醇和睾酮的变化与邻苯二甲酸代谢产物的变化相关，而黄体生成素的变化与邻苯二甲酸盐代谢产物的变化无关。结论：即使在低于RFDS的剂量下，邻苯二甲酸盐暴露也与精液质量和生殖激素的中断有关。然而，当暴露减少时，这些影响可能只会部分恢复，因此强调了更严格的邻苯二甲酸盐管理的紧迫性。
Background: Environment-Protection-Agency Reference Doses (EPA RfDs) for phthalate intakes are based on limited evidence, especially regarding low-dose male-reproductive toxicity. This study investigates the association between phthalate exposure and semen parameters and reproductive hormones in a general population with low phthalate exposure compared to the EPA RfDs.Methods: TheMARHCS (Male-Reproductive-Health-in-Chongqing-College-Students) cohort recruited 796 male students, who experienced a relocation of campuses and shifting environmental exposure. Urine, semen and blood before and after the relocation was collected and investigated for: (1) the associations between 13 urinary phthalate metabolites and 11 semen/hormone outcomes (five semen parameters including semen volume, sperm concentration, total sperm number, progressive motility, normal morphology) and six serum reproductive hormones including estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, progesterone, testosterone; (2) re-analysis of the metabolite-outcome associations in the subjects with estimated phthalate intakes below the RfDs; (3) a change in phthalate metabolites and change in semen/hormone outcomes after the relocation; (4) the association between these changes.Results: (1) All but two semen/hormone outcomes were associated with at least one phthalate metabolite, e.g., each quartile monoethyl phthalate was associated with a 5.3%, 5.7% and 2.6% decrease of sperm concentration, total sperm number and progressive motility respectively. (2) In the subjects with phthalate intakes below the RfDs, these metabolite-outcome associations remained significant. (3) All metabolites except mono(2-ethylhexyl) phthalate declined after relocation (P < 0.001 respectively); at the same time, semen volume, normal morphology, estradiol and luteinizing hormone increased (by 5.9%, 25.0%, 34.2% and 10.0%) and testosterone decreased (by 7.0%). (4) The changes in semen volume, normal morphology, estradiol and testosterone, but not the change in luteinizing hormone after relocation, were associated with the changes in the phthalate metabolites.Conclusions: Phthalate exposure is associated with interrupted semen quality and reproductive hormones in the human population even with a dose given below the RfDs. These effects, however, may only partially revert back when exposure decreases, thus emphasizing the urgency of stricter phthalate administration.