Shen Xilin, Génard-Walton Maximilien, Williams Paige L, Ford Jennifer B, Souter Irene, Allan Yazeed, Calafat Antonia M, Zhang Dan, Chavarro Jorge E, Hauser Russ, Mínguez-Alarcón Lidia
Institute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Environ Health Perspect. 2025 Jun;133(6):67005. doi: 10.1289/EHP15942. Epub 2025 Jun 6.
Phthalate exposures are ubiquitous and have been associated with pregnancy complications. Interaction between serum long-chain n-3 polyunsaturated fatty acids (n3PUFA) and phthalate biomarkers is biologically plausible because both can bind to human peroxisome proliferator-activated receptors (PPARs), which are involved in placenta development. However, evidence of this interaction in humans is lacking.
This study evaluated whether serum n3PUFA modifies the associations of biomarkers of phthalate exposure on pregnancy outcomes.
Among 351 women undergoing fertilization in the Environment and Reproductive Health study (2004-2017), we evaluated the effect modification of eicosapentaenoic acid (EPA) and serum docosahexaenoic acid (DHA) on the association of pregnancy outcomes with the mixture of urinary concentrations of phthalate biomarkers by quantile g-computation. All models were adjusted for age, body mass index, prior smoking, infertility diagnosis, treatment year, and urinary specific gravity.
Concentrations of the phthalate biomarkers mixture were associated with higher adjusted probabilities of pregnancy loss and lower estimated probabilities of live birth among women with serum in the lowest tertile ( of total fatty acids), but not among women with middle-to-high serum ( and 0.15, respectively). Among women in the lowest tertile of serum , the adjusted probability [95% confidence interval (CI)] of pregnancy loss for women in the lowest and highest quartile of phthalates mixtures was 5% (95% CI: 2%, 16%) and 44% (95% CI: 23%, 85%), respectively (). The corresponding estimates were 14% (95% CI: 5%, 41%) and 11% (95% CI: 3%, 42%) among women with serum in the highest tertile ( of total fatty acids) (). Similar trends were observed for live birth but not for implantation and clinical pregnancy.
This study suggests adverse effects of phthalate exposure on pregnancy loss and live birth may be attenuated by intakes of n3PUFA. These results, if replicated, could inform clinical practice reducing the burden of infertility by phthalate exposure among the general population and improving pregnancy outcomes among subfertile couples. https://doi.org/10.1289/EHP15942.
邻苯二甲酸盐暴露普遍存在，并与妊娠并发症有关。血清长链n-3多不饱和脂肪酸（n3PUFA）与邻苯二甲酸盐生物标志物之间的相互作用在生物学上是合理的，因为两者都可以与参与胎盘发育的人类过氧化物酶体增殖物激活受体（PPARs）结合。然而，人类中这种相互作用的证据尚缺乏。
本研究评估血清n3PUFA是否会改变邻苯二甲酸盐暴露生物标志物与妊娠结局之间的关联。
在环境与生殖健康研究（2004 - 2017年）中接受受精的351名女性中，我们通过分位数g计算评估了二十碳五烯酸（EPA）和血清二十二碳六烯酸（DHA）对妊娠结局与邻苯二甲酸盐生物标志物尿浓度混合物之间关联的效应修正。所有模型均根据年龄、体重指数、既往吸烟情况、不孕诊断、治疗年份和尿比重进行了调整。
邻苯二甲酸盐生物标志物混合物浓度与血清处于最低三分位数（总脂肪酸的 ）的女性中更高的流产调整概率和更低的活产估计概率相关，但在血清处于中高 （分别为 和0.15）的女性中并非如此。在血清处于最低三分位数的女性中，邻苯二甲酸盐混合物最低和最高四分位数的女性流产调整概率[95%置信区间（CI）]分别为5%（95%CI：2%，16%）和44%（95%CI：23%，85%）（ ）。在血清处于最高三分位数（总脂肪酸的 ）的女性中，相应的估计值分别为14%（95%CI：5%，41%）和11%（95%CI：3%，42%）（ ）。活产也观察到类似趋势，但着床和临床妊娠未观察到。
本研究表明，n3PUFA的摄入可能会减轻邻苯二甲酸盐暴露对流产和活产的不良影响。如果这些结果得到重复验证，可能会为临床实践提供参考，减轻普通人群中邻苯二甲酸盐暴露导致的不孕负担，并改善亚生育夫妇的妊娠结局。https://doi.org/10.1289/EHP15942 。
