The Possible Impact of Antenatal Exposure to Ubiquitous Phthalates Upon Male Reproductive Function at 20 Years of Age
The Possible Impact of Antenatal Exposure to Ubiquitous Phthalates Upon Male Reproductive Function at 20 Years of Age
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DOI：
10.3389/fendo.2018.00288
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发表时间：
2018-06-04
影响因子：
5.2
通讯作者：
Main, Katharina M.
中科院分区：
文献类型：
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作者：
Hart, Roger J.;Frederiksen, Hanne;Main, Katharina M.
邻苯二甲酸酯是普遍存在的环境内分泌干扰化学品，可能会干扰雄激素的发育作用，导致对男性生殖功能的不良影响。啮齿类动物的产前暴露研究显示，雄性动物会出现隐睾、尿道下裂和睾丸体积（TV）、睾酮和肛门生殖器距离缩小。据推测，当邻苯二甲酸酯暴露具有最强的不良反应时，子宫内存在发育窗口。一些人体研究表明，产前邻苯二甲酸酯暴露与男婴计算的“游离”血清睾酮减少和肛门生殖器距离缩短之间存在关联。然而，目前还没有数据表明产前接触与男性的长期影响之间的联系。我们的目的是将产前邻苯二甲酸酯暴露与成人TV、精液参数和血清生殖激素浓度相关联。来自西澳大利亚（Raine）妊娠队列的913名男性，年龄在20-22岁之间。423人（56%）同意参加; 404人接受睾丸超声检查; 365人提供精液样本，384人测量生殖激素。母亲产前血清邻苯二甲酸酯代谢物的测量可用于185和111名男子，谁提供的血清和精液，分别。收集妊娠18周和34周的母体血清，储存在-80 ℃下，通过液相色谱-串联质谱法分析32种邻苯二甲酸酯代谢物，计算TV，通过WHO批准的方法进行精液分析，并测量促性腺激素、促性腺激素B和睾酮的血清浓度。检测到11种邻苯二甲酸酯代谢物。邻苯二甲酸二（2-乙基己基）酯（DEHP）和邻苯二甲酸二异壬酯（DiNP）的初级和次级代谢产物呈正相关。校正成人身高后，BMI、精索静脉曲张和暴露于母亲吸烟邻苯二甲酸单异壬酯（MiNP）（r = -0.22）、DEHP和DiNP代谢产物总和（r = -0.24）以及高分子量邻苯二甲酸酯代谢产物总和（r = -0.21）与TV呈负相关（所有p < 0.05）。校正BMI后，成人血清总睾酮与以下暴露呈正相关：
Phthalates are ubiquitous environmental endocrine-disrupting chemicals suspected to interfere with developmental androgen action leading to adverse effects on male reproductive function. Prenatal exposure studies in rodents show cryptorchidism, hypospadias and reduced testicular volume (TV), testosterone and anogenital distance in males. It is postulated that there is a developmental window in utero when phthalate exposure has the most potent adverse effects. Some human studies show associations between prenatal phthalate exposure and reduced calculated "free" serum testosterone in infant boys and shorter anogenital distance. However, there are no data available yet which link antenatal exposure to long-term effects in men. We aimed to correlate antenatal phthalate exposure with adult TV, semen parameters and serum reproductive hormone concentrations. 913 men from the Western Australian (Raine) Pregnancy Cohort were contacted aged 20-22 years. 423 (56%) agreed to participate; 404 underwent testicular ultrasound examination; 365 provided semen samples, and reproductive hormones were measured in 384. Maternal antenatal serum phthalate metabolite measurements were available for 185 and 111 men, who provided serum and semen, respectively. Maternal serum collected at 18 and 34 weeks gestation, stored at -80 degrees C, was pooled and analyzed for 32 phthalate metabolites by liquid chromatography-tandem mass spectrometry, TV was calculated, semen analysis performed by WHO approved methods, and serum concentrations of gonadotrophins, inhibin B, and testosterone measured. Eleven phthalate metabolites were detected. Primary and secondary metabolites of di-(2-ethyl-hexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) were positively correlated. After correction for adult height, BMI, presence of a varicocele and exposure to maternal smoking mono-iso-nonyl phthalate (MiNP) (r = -0.22) and sums of DEHP and DiNP metabolites (r = -0.24) and the sum of the metabolites of the high molecular weight phthalates (r = -0.21) were negatively correlated with TV (all p < 0.05). After adjustment for BMI adult serum total testosterone was positively associated with exposure to the following