Environmental Health Program, Research Centre, King Faisal Specialist Hospital and Research Centre, PO Box: 3354, Riyadh 11211, Saudi Arabia.
Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, PO Box: 3354, Riyadh 11211, Saudi Arabia.
Sci Total Environ. 2019 Mar 25;658:982-995. doi: 10.1016/j.scitotenv.2018.12.261. Epub 2018 Dec 19.
Evidence from previous studies has shown that phthalates may play a role in male reproductive function; however, results are still inconclusive, and the mechanism remains unclear. In this study, we first assessed whether exposure to phthalates is associated with altered reproductive hormones and semen parameters in 599 men attending an in vitro fertilization clinic. Secondly, we evaluated whether reproductive hormones could play a mediating role in the association between phthalates and sperm parameters. Eight phthalate metabolites were measured in two different spot urine samples: mono‑n‑butyl phthalate, mono-isobutyl phthalate (MiBP), monoethyl phthalate (MEP), monobenzyl phthalate, and four oxidative metabolites of di‑(2‑ethylhexyl) phthalate (DEHP) [i.e., mono‑(2‑ethylhexyl) phthalate (MEHP), mono‑(2‑ethyl‑5‑hydroxyhexyl) phthalate (MEHHP), mono‑(2‑ethyl‑5‑oxohexyl) phthalate (MEOHP), and mono‑(2‑ethyl‑5‑carboxypentyl) phthalate (MECPP)]. Semen parameters (concentration, volume, motility, and morphology) and reproductive hormones, i.e., follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone, estradiol (E), testosterone (TEST) and prolactin (PROL) were also determined and considered the main study outcomes. Separate multivariate linear regression was used to assess associations between levels of each urinary phthalate metabolite, molar sum of DEHP metabolites (∑DEHP), percentage of MEHP to ∑DEHP (%MEHP), and each outcome (natural log-transformed). Inverse associations were observed between TEST and MiBP (β = -0.099), FSH and MEHHP (β = -0.087), and PROL and MEOHP (β = -0.102), while a positive relationship was seen between E and MEP (β = 0.098). %MEHP was associated positively with FSH (β = 0.118) and LH (β = 0.099), but negatively with TEST/LH (β = -0.086) and TEST/E (β = -0.109). Sperm concentration was associated positively with MECPP (β = 0.131), MEHHP (β = 0.117), MEOHP (β = 0.107) and ∑DEHP (β = 0.111), but negatively with %MEHP (β = -0.135). All p-values were <0.05. Sobel's test indicated that FSH mediated significantly up to 60% of the positive relationship between sperm concentration and MEHHP, while FSH and LH mediated respectively 15 and 12% of the inverse association between sperm concentration and %MEHP. Further research on this topic is warranted.
先前的研究证据表明，邻苯二甲酸酯可能会对男性生殖功能产生影响；然而，目前研究结果仍存在争议，其作用机制尚不清楚。在本研究中，我们首先评估了 599 名在体外受精诊所就诊的男性的邻苯二甲酸酯暴露是否与生殖激素和精液参数的改变有关。其次，我们评估了生殖激素是否可以在邻苯二甲酸酯和精子参数之间的关联中发挥中介作用。在两份不同的尿液样本中测量了 8 种邻苯二甲酸酯代谢物：单-正丁基邻苯二甲酸酯、单异丁基邻苯二甲酸酯（MiBP）、单乙基邻苯二甲酸酯（MEP）、单苄基邻苯二甲酸酯和邻苯二甲酸二（2-乙基己基）酯（DEHP）的四种氧化代谢物[即单（2-乙基己基）邻苯二甲酸酯（MEHP）、单（2-乙基-5-羟基己基）邻苯二甲酸酯（MEHHP）、单（2-乙基-5-氧己基）邻苯二甲酸酯（MEOHP）和单（2-乙基-5-羧基戊基）邻苯二甲酸酯（MECPP）]。精液参数（浓度、体积、活力和形态）和生殖激素，即卵泡刺激素（FSH）、黄体生成素（LH）、促甲状腺激素、雌二醇（E）、睾酮（TEST）和催乳素（PROL）也被测定并作为主要研究结果。使用单独的多变量线性回归来评估每个尿邻苯二甲酸酯代谢物、DEHP 代谢物的摩尔总和（∑DEHP）、MEHP 与∑DEHP 的百分比（%MEHP）与每个结果（自然对数转换）之间的关联。TEST 与 MiBP（β=−0.099）、FSH 与 MEHHP（β=−0.087）和 PROL 与 MEOHP（β=−0.102）之间存在负相关，而 E 与 MEP（β=0.098）之间存在正相关。%MEHP 与 FSH（β=0.118）和 LH（β=0.099）呈正相关，但与 TEST/LH（β=−0.086）和 TEST/E（β=−0.109）呈负相关。精子浓度与 MECPP（β=0.131）、MEHHP（β=0.117）、MEOHP（β=0.107）和∑DEHP（β=0.111）呈正相关，但与%MEHP（β=−0.135）呈负相关。所有 p 值均<0.05。Sobel 检验表明，FSH 显著介导了精子浓度与 MEHHP 之间正相关的 60%，而 FSH 和 LH 分别介导了精子浓度与%MEHP 之间负相关的 15%和 12%。需要进一步研究这个课题。
