孕期暴露于真菌雌激素和脐带血及母血清中甾体激素浓度的相关性:UPSIDE 妊娠队列研究

Associations between mycoestrogen exposure and sex steroid hormone concentrations in maternal serum and cord blood in the UPSIDE pregnancy cohort.

机构信息

Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ, USA.

Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ, USA; Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA.

出版信息

Int J Hyg Environ Health. 2024 Jul;260:114405. doi: 10.1016/j.ijheh.2024.114405. Epub 2024 Jun 14.

Abstract

Zearalenone (ZEN) is a fungal-derived toxin found in global food supplies including cereal grains and processed foods, impacting populations worldwide through diet. Because the chemical structure of ZEN and metabolites closely resembles 17β-estradiol (E2), they interact with estrogen receptors α/β earning their designation as 'mycoestrogens'. In animal models, gestational exposure to mycoestrogens disrupts estrogen activity and impairs fetal growth. Here, our objective was to evaluate relationships between mycoestrogen exposure and sex steroid hormone concentrations in maternal circulation and cord blood for the first time in humans. In each trimester, pregnant participants in the UPSIDE study (n = 297) provided urine for mycoestrogen analysis and serum for hormone analysis. At birth, placental mycoestrogens and cord steroids were measured. We fitted longitudinal models examining log-transformed mycoestrogen concentrations in relation to log-transformed hormones, adjusting for covariates. Secondarily, multivariable linear models examined associations at each time point (1st, 2nd, 3rd trimesters, delivery). We additionally considered effect modification by fetal sex. ZEN and its metabolite, α-zearalenol (α-ZOL), were detected in >93% and >75% of urine samples; >80% of placentas had detectable mycoestrogens. Longitudinal models from the full cohort exhibited few significant associations. In sex-stratified analyses, in pregnancies with male fetuses, estrone (E1) and free testosterone (fT) were inversely associated with ZEN (E1 %Δ: -6.68 95%CI: -12.34, -0.65; fT %Δ: -3.22 95%CI: -5.68, -0.70); while α-ZOL was positively associated with E2 (%Δ: 5.61 95%CI: -1.54, 9.85) in pregnancies with female fetuses. In analysis with cord hormones, urinary mycoestrogens were inversely associated with androstenedione (%Δ: 9.15 95%CI: 14.64, -3.30) in both sexes, and placental mycoestrogens were positively associated with cord fT (%Δ: 37.13, 95%CI: 4.86, 79.34) amongst male offspring. Findings support the hypothesis that mycoestrogens act as endocrine disruptors in humans, as in animal models and livestock. Additional work is needed to understand impacts on maternal and child health.

摘要

玉米赤霉烯酮(ZEN)是一种真菌衍生的毒素,存在于包括谷物和加工食品在内的全球食品供应中,通过饮食影响着全世界的人群。由于 ZEN 和代谢物的化学结构与 17β-雌二醇(E2)非常相似,它们与雌激素受体 α/β 相互作用,被称为“真菌雌激素”。在动物模型中,妊娠期暴露于真菌雌激素会破坏雌激素活性并损害胎儿生长。在这里,我们的目标是首次在人类中评估母体循环和脐带血中真菌雌激素暴露与性激素激素浓度之间的关系。在 UPSIDE 研究的每个三个月期间,(n=297),孕妇提供尿液进行真菌雌激素分析和血清进行激素分析。在出生时,测量胎盘真菌雌激素和脐带类固醇。我们拟合了纵向模型,以检查与激素对数变换相关的对数变换真菌雌激素浓度,同时调整协变量。其次,多变量线性模型在每个时间点(第 1、2、3 个三个月、分娩)检查关联。我们还考虑了胎儿性别对效应修饰的影响。ZEN 和其代谢物α-玉米赤霉烯醇(α-ZOL)在>93%和>75%的尿液样本中被检测到;>80%的胎盘有可检测到的真菌雌激素。来自全队列的纵向模型显示出很少有显著关联。在按性别分层的分析中,在具有男性胎儿的妊娠中,雌酮(E1)和游离睾酮(fT)与 ZEN 呈负相关(E1 %Δ:-6.68 95%CI:-12.34,-0.65;fT %Δ:-3.22 95%CI:-5.68,-0.70);而在具有女性胎儿的妊娠中,α-ZOL 与 E2 呈正相关(%Δ:5.61 95%CI:-1.54,9.85)。在用脐带激素进行分析时,尿真菌雌激素与雄烯二酮呈负相关(%Δ:9.15 95%CI:14.64,-3.30),在两性中,胎盘真菌雌激素与男性后代的脐带 fT 呈正相关(%Δ:37.13,95%CI:4.86,79.34)。研究结果支持这样的假设,即真菌雌激素在人类中作为内分泌干扰物发挥作用,就像在动物模型和牲畜中一样。需要进一步的工作来了解其对母婴健康的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ff/11441442/945f54b7dbee/nihms-2022539-f0001.jpg

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