TY - JOUR
T1 - Altered cord blood mitochondrial DNA content and pregnancy lead exposure in the PROGRESS cohort
AU - Sanchez-Guerra, Marco
AU - Peng, Cheng
AU - Trevisi, Letizia
AU - Cardenas, Andres
AU - Wilson, Ander
AU - Osorio-Yáñez, Citlalli
AU - Niedzwiecki, Megan M.
AU - Zhong, Jia
AU - Svensson, Katherine
AU - Acevedo, Maria Teresa
AU - Solano-Gonzalez, Maritsa
AU - Amarasiriwardena, Chitra J.
AU - Estrada-Gutierrez, Guadalupe
AU - Brennan, Kasey J.M.
AU - Schnaas, Lourdes
AU - Just, Allan C.
AU - Laue, Hannah E.
AU - Wright, Rosalind J.
AU - Téllez-Rojo, Martha Maria
AU - Wright, Robert O.
AU - Baccarelli, Andrea A.
N1 - Funding Information:
This work was supported by: R01ES013744; R01 ES021357; P30 ES023515; P30ES09089; and R01 ES014930; ABC – hospital and National Institute of Public Health (INSP), Mexico. MSG was financially supported by the Fundación México en Harvard , A.C. and Consejo Nacional de Ciencia y Tecnología (CONACYT, Mexico).
Publisher Copyright:
© 2019
PY - 2019/4
Y1 - 2019/4
N2 - Introduction: Lead (Pb) crosses the placenta and can cause oxidative stress, reduced fetal growth and neurological problems. The principal source of oxidative stress in human cells is mitochondria. Therefore, disruption of normal mitochondrial function during pregnancy may represent a primary mechanism behind the adverse effects of lead. We sought to assess the association of Pb exposure during pregnancy with mitochondrial DNA (mtDNA) content, a sensitive marker of mitochondrial function, in cord blood. Materials and methods: This study comprised mother-infant pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a prospective birth-cohort that enrolled 1050 pregnant women from Mexico City who were receiving prenatal care between December 2007 and July 2011. Quantitative PCR was used to calculate relative MtDNA content (mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA)) in cord blood. Lead concentrations in both maternal blood (2nd and 3rd trimester and at delivery day) and in cord blood were measured by ICP-MS. Multivariable regression models adjusting for multiple confounders were fitted with 410 mother-infant pairs for whom complete data for mtDNA content, lead levels, and covariates were available. Results: Maternal blood Pb measured in the second (mean 3.79 μg/dL, SD 2.63; β = 0.059, 95% CI 0.008, 0.111) and third trimester (mean 3.90 μg/dL; SD 2.84; β = 0.054, 95% CI 0.002, 0.107) during pregnancy and PB in cord blood (mean 3.50 μg/dL, SD 2.59; β = 0.050, 95% CI 0.004; 0.096) were associated with increased cord blood mtDNA content (mean 1.46, SD 0.44). In two-way interaction analyses, cord blood Pb marginally interacted with gestational age leading to an increase in mtDNA content for pre-term births (Benjamini-Hochberg False Discovery Rate correction; BH-FDR = 0.08). Conclusion: This study shows that lead exposure in pregnancy alters mtDNA content in cord blood; therefore, alteration of mtDNA content might be a mechanism underlying the toxicity of lead.
AB - Introduction: Lead (Pb) crosses the placenta and can cause oxidative stress, reduced fetal growth and neurological problems. The principal source of oxidative stress in human cells is mitochondria. Therefore, disruption of normal mitochondrial function during pregnancy may represent a primary mechanism behind the adverse effects of lead. We sought to assess the association of Pb exposure during pregnancy with mitochondrial DNA (mtDNA) content, a sensitive marker of mitochondrial function, in cord blood. Materials and methods: This study comprised mother-infant pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a prospective birth-cohort that enrolled 1050 pregnant women from Mexico City who were receiving prenatal care between December 2007 and July 2011. Quantitative PCR was used to calculate relative MtDNA content (mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA)) in cord blood. Lead concentrations in both maternal blood (2nd and 3rd trimester and at delivery day) and in cord blood were measured by ICP-MS. Multivariable regression models adjusting for multiple confounders were fitted with 410 mother-infant pairs for whom complete data for mtDNA content, lead levels, and covariates were available. Results: Maternal blood Pb measured in the second (mean 3.79 μg/dL, SD 2.63; β = 0.059, 95% CI 0.008, 0.111) and third trimester (mean 3.90 μg/dL; SD 2.84; β = 0.054, 95% CI 0.002, 0.107) during pregnancy and PB in cord blood (mean 3.50 μg/dL, SD 2.59; β = 0.050, 95% CI 0.004; 0.096) were associated with increased cord blood mtDNA content (mean 1.46, SD 0.44). In two-way interaction analyses, cord blood Pb marginally interacted with gestational age leading to an increase in mtDNA content for pre-term births (Benjamini-Hochberg False Discovery Rate correction; BH-FDR = 0.08). Conclusion: This study shows that lead exposure in pregnancy alters mtDNA content in cord blood; therefore, alteration of mtDNA content might be a mechanism underlying the toxicity of lead.
KW - Cord blood
KW - Lead exposure
KW - Mitochondrial dysfunction
KW - Pregnancy
KW - mtDNA content
UR - http://www.scopus.com/inward/record.url?scp=85061322946&partnerID=8YFLogxK
U2 - 10.1016/j.envint.2019.01.077
DO - 10.1016/j.envint.2019.01.077
M3 - Article
C2 - 30753999
AN - SCOPUS:85061322946
SN - 0160-4120
VL - 125
SP - 437
EP - 444
JO - Environment international
JF - Environment international
ER -