Main Katharina M, Mortensen Gerda K, Kaleva Marko M, Boisen Kirsten A, Damgaard Ida N, Chellakooty Marla, Schmidt Ida M, Suomi Anne-Maarit, Virtanen Helena E, Petersen Dajørgen Vid H, Andersson Anna-Maria, Toppari Jorma, Skakkebaek Niels E
University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.
Environ Health Perspect. 2006 Feb;114(2):270-6. doi: 10.1289/ehp.8075.
Phthalates adversely affect the male reproductive system in animals. We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis.
We obtained biologic samples from a prospective Danish-Finnish cohort study on cryptorchidism from 1997 to 2001. We analyzed individual breast milk samples collected as additive aliquots 1-3 months postnatally (n = 130; 62 cryptorchid/68 healthy boys) for phthalate monoesters [mono-methyl phthalate (mMP), mono-ethyl phthalate (mEP), mono-n-butyl phthalate (mBP), mono-benzyl phthalate (mBzP), mono-2-ethylhexyl phthalate (mEHP), mono-isononyl phthalate (miNP)]. We analyzed serum samples (obtained in 74% of all boys) for gonadotropins, sex-hormone binding globulin (SHBG), testosterone, and inhibin B.
All phthalate monoesters were found in breast milk with large variations [medians (minimum-maximum)]: mMP 0.10 (< 0.01-5.53 microg/L), mEP 0.95 (0.07-41.4 microg/L), mBP 9.6 (0.6-10,900 microg/L), mBzP 1.2 (0.2-26 microg/L), mEHP 11 (1.5-1,410 microg/L), miNP 95 (27-469 microg/L). Finnish breast milk had higher concentrations of mBP, mBzP, mEHP, and Danish breast milk had higher values for miNP (p = 0.0001-0.056). No association was found between phthalate monoester levels and cryptorchidism. However, mEP and mBP showed positive correlations with SHBG (r = 0.323, p = 0.002 and r = 0.272, p = 0.01, respectively); mMP, mEP, and mBP with LH:free testosterone ratio (r = 0.21-0.323, p = 0.002-0.044) and miNP with luteinizing hormone (r = 0.243, p = 0.019). mBP was negatively correlated with free testosterone (r = -0.22, p = 0.033). Other phthalate monoesters showed similar but nonsignificant tendencies.
Our data on reproductive hormone profiles and phthalate exposures in newborn boys are in accordance with rodent data and suggest that human Leydig cell development and function may also be vulnerable to perinatal exposure to some phthalates. Our findings are also in line with other recent human data showing incomplete virilization in infant boys exposed to phthalates prenatally.
邻苯二甲酸盐会对动物的雄性生殖系统产生不利影响。我们调查了人乳中邻苯二甲酸单酯污染是否会对新生男婴出生后生殖激素的激增产生影响，以此作为睾丸发育异常的一个迹象。
我们从1997年至2001年一项关于隐睾症的丹麦 - 芬兰前瞻性队列研究中获取生物样本。我们分析了产后1 - 3个月收集的作为附加等分试样的个体母乳样本（n = 130；62例隐睾症男婴/68例健康男婴）中的邻苯二甲酸单酯[邻苯二甲酸单甲酯（mMP）、邻苯二甲酸单乙酯（mEP）、邻苯二甲酸单正丁酯（mBP）、邻苯二甲酸单苄酯（mBzP）、邻苯二甲酸单（2 - 乙基己基）酯（mEHP）、邻苯二甲酸单异壬酯（miNP）]。我们分析了血清样本（在所有男婴的74%中获取）中的促性腺激素、性激素结合球蛋白（SHBG）、睾酮和抑制素B。
在母乳中发现了所有邻苯二甲酸单酯，且差异很大[中位数（最小值 - 最大值）]：mMP 0.10（< 0.01 - 5.53微克/升），mEP 0.95（0.07 - 41.4微克/升），mBP 9.6（0.6 - 10900微克/升），mBzP 1.2（0.2 - 26微克/升），mEHP 11（1.5 - 1410微克/升），miNP 95（27 - 469微克/升）。芬兰母乳中mBP、mBzP、mEHP的浓度较高，丹麦母乳中miNP的值较高（p = 0.0001 - 0.056）。未发现邻苯二甲酸单酯水平与隐睾症之间存在关联。然而，mEP和mBP与SHBG呈正相关（r = 0.323，p = 0.002和r = 0.272，p = 0.01）；mMP、mEP和mBP与促黄体生成素：游离睾酮比值呈正相关（r = 0.21 - 0.323，p = 0.002 - 0.044），miNP与促黄体生成素呈正相关（r = 0.243，p = 0.019）。mBP与游离睾酮呈负相关（r = -0.22，p = 0.033）。其他邻苯二甲酸单酯显示出类似但不显著的趋势。
我们关于新生男婴生殖激素谱和邻苯二甲酸酯暴露的数据与啮齿动物数据一致，表明人类睾丸间质细胞的发育和功能可能也易受围产期接触某些邻苯二甲酸酯的影响。我们的研究结果也与其他近期人类数据相符，这些数据显示产前接触邻苯二甲酸酯的男婴存在不完全男性化的情况。
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