Sathyanarayana Sheela, Butts Samantha, Wang Christina, Barrett Emily, Nguyen Ruby, Schwartz Stephen M, Haaland Wren, Swan Shanna H
Department of Pediatrics, University of Washington, Seattle, Washington 98121.
Seattle Children's Research Institute, Center for Child Health, Behavior, and Development, Seattle, Washington 98121.
J Clin Endocrinol Metab. 2017 Jun 1;102(6):1870-1878. doi: 10.1210/jc.2016-3837.
Adequate sex steroid hormone concentrations are essential for normal fetal genital development in early pregnancy. Our previous study demonstrated an inverse relationship between third-trimester di-2-ethyl hexyl phthalate exposure and total testosterone (TT) concentrations. Here, we examine early-pregnancy phthalates, sex steroid hormone concentrations, and newborn reproductive outcomes.
We examined associations between urinary phthalate metabolite concentrations in early pregnancy and serum free testosterone (FT), TT, estrone (E1), and estradiol (E2) in 591 woman/infant dyads in The Infant Development and Environment Study; we also examined relationships between hormones and newborn genital outcomes using multiple regression models with covariate adjustment.
E1 and E2 concentrations were 15% to 30% higher in relation to 1-unit increases in log monoisobutyl phthalate (MiBP), mono-2-ethyl hexyl phthalate, and mono-2-ethyl-5-oxy-hexyl phthalate concentrations, and E2 was 15% higher in relation to increased log monobenzyl phthalate (MBzP). FT concentrations were 12% lower in relation to 1-unit increases in log mono(carboxynonyl) phthalate (MCNP) and mono-2-ethyl-5-carboxypentyl phthalate concentrations. Higher maternal FT was associated with a 25% lower prevalence of having a male genital abnormality at birth.
The positive relationships between MiBP, MBzP, and DEHP metabolites and E1/E2 are unique and suggest a positive estrogenic effect in early pregnancy. The inverse relationship between MCNP and DEHP metabolites and serum FT supports previous work examining phthalate/testosterone relationships later in pregnancy. Higher FT in relation to a 25% lower prevalence of male genital abnormalities confirms the importance of testosterone in early fetal development.
足够的性类固醇激素浓度对妊娠早期胎儿正常生殖器发育至关重要。我们之前的研究表明，孕晚期邻苯二甲酸二（2-乙基己基）酯暴露与总睾酮（TT）浓度之间存在负相关关系。在此，我们研究妊娠早期邻苯二甲酸盐、性类固醇激素浓度与新生儿生殖结局。
我们在婴儿发育与环境研究中，检测了591对母婴二元组中妊娠早期尿中邻苯二甲酸酯代谢物浓度与血清游离睾酮（FT）、TT、雌酮（E1）和雌二醇（E2）之间的关联；我们还使用多变量回归模型并进行协变量调整，研究了激素与新生儿生殖器结局之间的关系。
与邻苯二甲酸单异丁酯（MiBP）、邻苯二甲酸单（2-乙基己基）酯和邻苯二甲酸单（2-乙基-5-氧代己基）酯浓度每增加1个对数单位相比，E1和E2浓度升高15%至30%，与邻苯二甲酸单苄酯（MBzP）浓度升高相比，E2浓度升高15%。与邻苯二甲酸单（羧基壬基）酯（MCNP）和邻苯二甲酸单（2-乙基-5-羧基戊基）酯浓度每增加1个对数单位相比，FT浓度降低12%。母亲FT水平较高与出生时男性生殖器异常患病率降低25%相关。
MiBP、MBzP和邻苯二甲酸二（2-乙基己基）酯代谢物与E1/E2之间的正相关关系是独特的，提示在妊娠早期存在正向雌激素效应。MCNP和邻苯二甲酸二（2-乙基己基）酯代谢物与血清FT之间的负相关关系支持了之前关于妊娠后期邻苯二甲酸盐/睾酮关系的研究。FT水平较高与男性生殖器异常患病率降低25%相关，证实了睾酮在胎儿早期发育中的重要性。
