TY - JOUR
T1 - Prenatal manganese and cord blood mitochondrial DNA copy number
T2 - Effect modification by maternal anemic status
AU - Kupsco, Allison
AU - Sanchez-Guerra, Marco
AU - Amarasiriwardena, Chitra
AU - Brennan, Kasey J.M.
AU - Estrada-Gutierrez, Guadalupe
AU - Svensson, Katherine
AU - Schnaas, Lourdes
AU - Pantic, Ivan
AU - Téllez-Rojo, Martha María
AU - Baccarelli, Andrea A.
AU - Wright, Robert O.
N1 - Funding Information:
This work was supported by NIEHS grants: R01ES014930 ; R01ES013744 R01ES021357 , P30ES009089 , P30ES023515 , and R24ES028522 . Co-Investigators and staff at the INSP were also supported and received partial funding from the National Institute of Public Health/Ministry of Health of Mexico. The authors would like to thank the American British Cowdray Hospital in Mexico City, Mexico, for providing research facilities. MSG was financially supported by the Fundación México en Harvard, A.C.
Funding Information:
This work was supported by NIEHS grants: R01ES014930; R01ES013744 R01ES021357, P30ES009089, P30ES023515, and R24ES028522. Co-Investigators and staff at the INSP were also supported and received partial funding from the National Institute of Public Health/Ministry of Health of Mexico. The authors would like to thank the American British Cowdray Hospital in Mexico City, Mexico, for providing research facilities. MSG was financially supported by the Fundación México en Harvard, A.C.
Publisher Copyright:
© 2019 The Authors
PY - 2019/5
Y1 - 2019/5
N2 - Introduction: Manganese (Mn) is an essential nutrient but also a toxicant at high exposures, when it can induce oxidative stress (OS). Mn uptake is inversely correlated with iron status, therefore anemic individuals may be more susceptible to Mn overload induced-OS, which can manifest as changes in mitochondrial DNA copy number (mtDNA CN). Our objectives were to: 1) determine stage-specific associations of prenatal Mn exposure with cord blood MtDNA CN; and 2) investigate effect modification by maternal anemia, ferritin, and mean corpuscular volume (MCV). Materials and methods: We measured whole blood Mn, hemoglobin, serum ferritin, and MCV in the 2nd and 3rd trimester, in maternal blood at birth, and in cord blood from a prospective birth cohort in Mexico City, Mexico (n = 485). We then extracted DNA from cord blood leukocytes to determine mtDNA CN. We used robust regression to measure associations between Mn and mtDNA CN at each trimester and at birth. Anemia (hemoglobin ≤11 g/dL), iron deficiency (ferritin ≤15 ng/mL) and MCV (stratified at median), were examined as effect modifiers. Results: Mn levels increased throughout pregnancy, and Mn was inversely correlated with ferritin. We observed a positive association between Mn in the 3rd trimester and Mn in cord blood and mtDNA CN (β = 0.04–0.05; 95% CI = 0.01, 0.08). Anemia significantly modified the association between mtDNA CN and Mn in the 2nd trimester. We found a positive association between 2nd trimester Mn and mtDNA CN in mothers with normal hemoglobin, and a negative association in those with low hemoglobin. (βhigh = 0.06; 95% CI = 0.01, 0.11; p = 0.01 and βlow = −0.06; 95% CI = 0.03, −0.13; p = 0.06). No associations were detected between anemia, iron deficiency and MCV and mtDNA CN. Conclusions: Maternal blood Mn in the 3rd trimester and in cord blood was positively associated with mtDNA CN, suggesting that higher late pregnancy prenatal Mn exposures can impact newborn mitochondria by promoting OS. Furthermore, 2nd trimester Mn was positively associated with mtDNA in non-anemic mother-child pairs but inversely associated in anemic individuals, indicating potential interactions between Mn and chronic anemia.
AB - Introduction: Manganese (Mn) is an essential nutrient but also a toxicant at high exposures, when it can induce oxidative stress (OS). Mn uptake is inversely correlated with iron status, therefore anemic individuals may be more susceptible to Mn overload induced-OS, which can manifest as changes in mitochondrial DNA copy number (mtDNA CN). Our objectives were to: 1) determine stage-specific associations of prenatal Mn exposure with cord blood MtDNA CN; and 2) investigate effect modification by maternal anemia, ferritin, and mean corpuscular volume (MCV). Materials and methods: We measured whole blood Mn, hemoglobin, serum ferritin, and MCV in the 2nd and 3rd trimester, in maternal blood at birth, and in cord blood from a prospective birth cohort in Mexico City, Mexico (n = 485). We then extracted DNA from cord blood leukocytes to determine mtDNA CN. We used robust regression to measure associations between Mn and mtDNA CN at each trimester and at birth. Anemia (hemoglobin ≤11 g/dL), iron deficiency (ferritin ≤15 ng/mL) and MCV (stratified at median), were examined as effect modifiers. Results: Mn levels increased throughout pregnancy, and Mn was inversely correlated with ferritin. We observed a positive association between Mn in the 3rd trimester and Mn in cord blood and mtDNA CN (β = 0.04–0.05; 95% CI = 0.01, 0.08). Anemia significantly modified the association between mtDNA CN and Mn in the 2nd trimester. We found a positive association between 2nd trimester Mn and mtDNA CN in mothers with normal hemoglobin, and a negative association in those with low hemoglobin. (βhigh = 0.06; 95% CI = 0.01, 0.11; p = 0.01 and βlow = −0.06; 95% CI = 0.03, −0.13; p = 0.06). No associations were detected between anemia, iron deficiency and MCV and mtDNA CN. Conclusions: Maternal blood Mn in the 3rd trimester and in cord blood was positively associated with mtDNA CN, suggesting that higher late pregnancy prenatal Mn exposures can impact newborn mitochondria by promoting OS. Furthermore, 2nd trimester Mn was positively associated with mtDNA in non-anemic mother-child pairs but inversely associated in anemic individuals, indicating potential interactions between Mn and chronic anemia.
KW - Anemia
KW - Iron deficiency
KW - Manganese
KW - Mitochondria
KW - Mitochondrial DNA
KW - Prenatal exposure
UR - http://www.scopus.com/inward/record.url?scp=85062279772&partnerID=8YFLogxK
U2 - 10.1016/j.envint.2019.02.029
DO - 10.1016/j.envint.2019.02.029
M3 - Article
C2 - 30849576
AN - SCOPUS:85062279772
SN - 0160-4120
VL - 126
SP - 484
EP - 493
JO - Environment international
JF - Environment international
ER -