Institute of Environmental Medicine, Karolinska Institutet, P.O. Box 210, SE-171 77, Stockholm, Sweden.
Current Address: Department of Environmental Research and Monitoring, Swedish Museum of Natural History, Stockholm, Sweden.
BMC Med. 2019 Apr 11;17(1):77. doi: 10.1186/s12916-019-1309-6.
The uterine environment may influence telomere length at birth, which is essential for cellular function, aging, and disease susceptibility over the lifespan. However, little is known about the impact of toxic chemicals on early-life telomeres. Therefore, we assessed the potential impact of multiple toxic metals on relative telomere length (rTL) in the maternal blood, cord blood, and placenta, as well as the potential modifying effects of pro-oxidants.
In a mother-child cohort in northern Argentina (n = 169), we measured multiple toxic metals in the maternal blood or urine collected during late pregnancy, as well as the placenta and cord blood collected at delivery, using inductively coupled plasma mass spectrometry (ICP-MS). We assessed associations of log-transformed metal concentrations with rTL, measured in maternal and cord blood leukocytes and the placenta by real-time PCR, using multivariable-adjusted linear regression. Additionally, we tested for modifications by antioxidants (zinc, selenium, folate, and vitamin D).
Exposure to boron and antimony during pregnancy was associated with shorter maternal rTL, and lithium with longer maternal rTL; a doubling of exposure was associated with changes corresponding to 0.2-0.4 standard deviations (SD) of the rTL. Arsenic concentrations in the placenta (n = 98), blood, and urine were positively associated with placental rTL, about 0.2 SD by doubled arsenic. In the cord blood (n = 88), only lead was associated with rTL (inversely), particularly in boys (p for interaction 0.09). Stratifying by newborn sex showed ten times stronger association in boys (about 0.6 SD) than in girls. The studied antioxidants did not modify the associations, except that with antimony.
Elevated exposure to boron, lithium, arsenic, and antimony was associated with maternal or newborn rTL in a tissue-specific, for lead also sex-specific, manner. Nutritional antioxidants did not generally influence the associations.
子宫环境可能会影响出生时的端粒长度，这对于细胞功能、衰老和整个生命周期中的疾病易感性至关重要。然而，人们对有毒化学物质对生命早期端粒的影响知之甚少。因此，我们评估了多种有毒金属对母亲血液、脐带血和胎盘相对端粒长度（rTL）的潜在影响，以及氧化剂的潜在修饰作用。
在阿根廷北部的一项母婴队列研究中（n=169），我们使用电感耦合等离子体质谱法（ICP-MS）测量了孕妇血液或尿液中多种有毒金属的浓度，以及分娩时采集的胎盘和脐带血。我们使用实时 PCR 测量了母亲和脐带血白细胞以及胎盘的 rTL，并使用多变量调整线性回归评估了 log 转换金属浓度与 rTL 的关联。此外，我们还测试了抗氧化剂（锌、硒、叶酸和维生素 D）的修饰作用。
怀孕期间硼和锑的暴露与母亲 rTL 缩短有关，而锂与母亲 rTL 延长有关；暴露量增加一倍与 rTL 的变化相对应，变化值为 rTL 的 0.2-0.4 个标准差（SD）。胎盘（n=98）、血液和尿液中的砷浓度与胎盘 rTL 呈正相关，砷浓度增加一倍，胎盘 rTL 增加约 0.2 SD。在脐带血（n=88）中，只有铅与 rTL 呈负相关（相反），尤其是在男孩中（交互作用的 p 值为 0.09）。按新生儿性别分层显示，男孩的关联强度比女孩强十倍（约 0.6 SD）。所研究的抗氧化剂除了对锑的影响外，一般不会改变这些关联。
硼、锂、砷和锑的暴露水平升高与母亲或新生儿 rTL 呈组织特异性，对铅而言还呈性别特异性相关。营养抗氧化剂通常不会影响这些关联。
