Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Environ Health. 2020 Nov 25;19(1):124. doi: 10.1186/s12940-020-00672-0.
Endocrine disrupting chemicals (EDCs) such as metals have been reported to alter circulating reproductive hormone concentrations and pubertal development in animals. However, the relationship has rarely been investigated among humans, with the exception of heavy metals, such as Pb and Cd. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone concentrations and sexual maturation and progression among boys from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts.
Our analysis included 118 pregnant women and their male children from the ELEMENT study. Essential and non-essential metals were measured in urine collected from the mothers during the third trimester of pregnancy and their male children at 8-14 years. Reproductive hormone concentrations [serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG)] were measured in blood samples from the children at 8-14 years. We also assessed Tanner stages for sexual maturation (genital, pubic hair development, and testicular volume), at two time points (8-14, 10-18 years). We used linear regression to independently examine urinary metal concentrations in relation to each peripubertal reproductive hormones adjusting for child age and BMI. Generalized estimation equations (GEEs) were used to evaluate the association of in utero and peripubertal metal exposures with sexual maturation and progression during follow-up based on Tanner staging and testicular volume.
In utero and prepubertal concentrations of some urinary metals were associated with increased concentrations of peripubertal reproductive hormones, especially non-essential metal(loid)s As and Cd (in utero), and Ba (peripubertal) as well as essential metal Mo (in utero) in association with testosterone. More advanced pubic hair developmental stage and higher testicular volume at the early teen visit was observed for boys with higher non-essential metal concentrations, including in utero Al and peripubertal Ba, and essential metal Zn concentration (peripubertal). These metals were also associated with slower pubertal progression between the two visits.
These findings suggest that male reproductive development may be associated with both essential and non-essential metal exposure during in utero and peripubertal windows.
已有研究报道,内分泌干扰化学物质(EDCs),如金属,可改变动物的循环生殖激素浓度和青春期发育。然而,除了重金属如铅(Pb)和镉(Cd)之外,人类中很少有研究调查这种关系。我们的目的是研究宫内和青春期金属暴露与男性儿童生殖激素浓度以及性成熟和发育的关系,这些男性儿童来自墨西哥早期环境暴露于环境毒物(ELEMENT)队列。
我们的分析包括来自 ELEMENT 研究的 118 名孕妇及其男性儿童。在孕妇妊娠晚期和其男性儿童 8-14 岁时,采集尿液测量必需和非必需金属。在儿童 8-14 岁时,采集血液样本测量生殖激素浓度[血清睾酮、雌二醇、脱氢表雄酮硫酸酯(DHEA-S)、抑制素 B 和性激素结合球蛋白(SHBG)]。我们还在两个时间点(8-14 岁、10-18 岁)评估了性成熟的 Tanner 分期(生殖器、阴毛发育和睾丸体积)。我们使用线性回归分别检查了与每个青春期生殖激素相关的尿液金属浓度,调整了儿童年龄和 BMI。基于 Tanner 分期和睾丸体积,使用广义估计方程(GEE)评估宫内和青春期金属暴露与随访期间性成熟和发育的关系。
宫内和青春期前的某些尿液金属浓度与青春期生殖激素浓度升高有关,尤其是非必需金属(类)砷(As)和镉(宫内)和钡(青春期)以及必需金属钼(宫内)与睾酮有关。在青少年早期就诊时,具有较高非必需金属浓度(包括宫内铝和青春期前钡以及必需金属锌浓度)的男孩的阴毛发育阶段更早,睾丸体积更大。这些金属也与两次就诊之间的青春期进展较慢有关。
这些发现表明,男性生殖发育可能与宫内和青春期暴露于必需和非必需金属有关。