Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Gaotanyan St 30, Chongqing 400038, China.
Chongqing Institute of Science and Technology for Population and Family Planning, Yangheercun 5, Chongqing 401147, China.
Environ Int. 2017 Jul;104:58-68. doi: 10.1016/j.envint.2017.04.005. Epub 2017 Apr 25.
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.
The MARHCS (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.
(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.
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.
邻苯二甲酸酯摄入量的环保署参考剂量（EPA RfD）基于有限的证据，特别是关于低剂量雄性生殖毒性的证据。本研究调查了在低邻苯二甲酸酯暴露的一般人群中，邻苯二甲酸酯暴露与精液参数和生殖激素之间的关系，与 EPA RfD 相比。
MARHCS（重庆大学生男性生殖健康）队列招募了 796 名男学生，他们经历了校园搬迁和环境暴露的转变。在搬迁前后采集了尿液、精液和血液，并对以下内容进行了调查：（1）13 种尿邻苯二甲酸酯代谢物与 11 种精液/激素结果（包括精液量、精子浓度、总精子数、前向运动精子、正常形态）之间的关联和六种血清生殖激素（包括雌二醇、卵泡刺激素、黄体生成素、催乳素、孕酮、睾丸激素）；（2）在估计摄入量低于 RfD 的受试者中对代谢物-结果关联进行重新分析；（3）搬迁后的邻苯二甲酸代谢物和精液/激素结果的变化；（4）这些变化之间的关联。
（1）除了两个生殖激素结果外，所有其他的精液/生殖激素结果都与至少一种邻苯二甲酸酯代谢物有关，例如，单乙基邻苯二甲酸酯的每个四分位数分别与精子浓度、总精子数和前向运动精子的浓度降低 5.3%、5.7%和 2.6%有关。（2）在摄入量低于 RfD 的受试者中，这些代谢物-结果关联仍然显著。（3）除了单（2-乙基己基）邻苯二甲酸酯外，所有代谢物在搬迁后均下降（分别为 P<0.001）；与此同时，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%），睾丸激素减少（减少 7.0%）。（4）搬迁后精液量、正常形态、雌二醇和睾丸激素的变化与邻苯二甲酸代谢物的变化有关，但黄体生成素的变化除外。
即使在低于 RfD 的剂量下，邻苯二甲酸酯的暴露也与人类人群的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酯管理的紧迫性。
