Abstract
BackgroundThe 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.MethodIn 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 log2-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 D3).ResultsExposure 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.ConclusionsElevated 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.
Highlights
The uterine environment may influence telomere length at birth, which is essential for cellular function, aging, and disease susceptibility over the lifespan
Exposure to boron and antimony during pregnancy was associated with shorter maternal relative telomere length (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
In the cord blood (n = 88), only lead was associated with rTL, in boys (p for interaction 0.09)
Summary
The uterine environment may influence telomere length at birth, which is essential for cellular function, aging, and disease susceptibility over the lifespan. Telomeres are nucleotide sequences at the end of chromosomes of importance for maintaining genomic integrity [1, 2] They are shortened by each cell division as a normal cellular process, eventually reaching a critically short length of the chromosomes that activates the replicative senescence and aging of tissues and organs and, in turn, increases the risk of diseases [3]. There is emerging evidence that factors, such as maternal obesity [10], stress [11, 12], and smoking [13, 14], may influence child TL This may have long-term effects, as TL at birth is believed to contribute substantially to the TL throughout life [5, 15, 16]
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