Yiyi Xu1, Karin Wahlberg2, Tanzy M Love3, Gene E Watson3, Alison J Yeates4, Maria S Mulhern4, Emeir M McSorley4, J J Strain4, Philip W Davidson3, Conrad F Shamlaye5, Matthew D Rand3, G J Myers3, Edwin van Wijngaarden3, Karin Broberg6. 1. Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, 22185 Lund, Sweden; Unit of Occupational and Environmental Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. 2. Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, 22185 Lund, Sweden. 3. University of Rochester Medical Center, School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, NY 14642, USA. 4. Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Cromore Road, Coleraine BT52 1SA, Co. Londonderry, UK. 5. the Child Development Centre, Ministry of Health, Mahé, Seychelles. 6. Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, 22185 Lund, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden. Electronic address: karin.broberg@ki.se.
Abstract
BACKGROUND: Fish contains methylmercury (MeHg) which can cause oxidative stress and neurodevelopmental toxicity at sufficiently high doses. Fish also contains polyunsaturated fatty acids (PUFA) which have both antioxidant (n-3) and oxidant (n-6) properties. Mitochondrial DNA (mtDNA) is sensitive to oxidative stress but has not been previously studied in relation to MeHg exposure or PUFA status. OBJECTIVE: To investigate the associations between MeHg exposure and PUFA status during pregnancy with relative mitochondrial DNA copy number (RmtDNAcn) in mothers and their newborns. METHODS: In total, 1488 mother-child pairs from the Seychelles Child Development Study Nutrition Cohort 2 were included in this study. Total Hg was measured in maternal blood collected at 28 weeks' gestation, maternal hair at delivery, and in fetal cord blood. PUFA (n-3 and n-6) were measured only in maternal blood. RmtDNAcn was measured by qPCR in both maternal and cord blood. RESULTS: Increasing maternal blood Hg (β = 0.001, 95%CI: 0.000, 0.002) and n-3 PUFA concentrations (β = 0.183, 95%CI: 0.048, 0.317) were associated with higher maternal RmtDNAcn. Increasing maternal n-6 PUFA (β = -0.103, 95%CI: -0.145, -0.062) and n-6/n-3 ratio (β = -0.011, 95%CI: -0.017, -0.004) were associated with lower maternal RmtDNAcn. Increasing fetal cord blood Hg was associated with lower fetal RmtDNAcn (β = -0.002, 95%CI: -0.004, -0.000). Neither maternal blood Hg nor PUFA status was associated with fetal RmtDNAcn. CONCLUSIONS: Our findings suggest that MeHg and PUFA may influence mitochondrial homeostasis although the magnitude of these associations are small. Future studies should confirm the findings and explore the underlying mechanisms.
BACKGROUND: Fish contains methylmercury (MeHg) which can cause oxidative stress and neurodevelopmental toxicity at sufficiently high doses. Fish also contains polyunsaturated fatty acids (PUFA) which have both antioxidant (n-3) and oxidant (n-6) properties. Mitochondrial DNA (mtDNA) is sensitive to oxidative stress but has not been previously studied in relation to MeHg exposure or PUFA status. OBJECTIVE: To investigate the associations between MeHg exposure and PUFA status during pregnancy with relative mitochondrial DNA copy number (RmtDNAcn) in mothers and their newborns. METHODS: In total, 1488 mother-child pairs from the Seychelles Child Development Study Nutrition Cohort 2 were included in this study. Total Hg was measured in maternal blood collected at 28 weeks' gestation, maternal hair at delivery, and in fetal cord blood. PUFA (n-3 and n-6) were measured only in maternal blood. RmtDNAcn was measured by qPCR in both maternal and cord blood. RESULTS: Increasing maternal blood Hg (β = 0.001, 95%CI: 0.000, 0.002) and n-3 PUFA concentrations (β = 0.183, 95%CI: 0.048, 0.317) were associated with higher maternal RmtDNAcn. Increasing maternal n-6 PUFA (β = -0.103, 95%CI: -0.145, -0.062) and n-6/n-3 ratio (β = -0.011, 95%CI: -0.017, -0.004) were associated with lower maternal RmtDNAcn. Increasing fetal cord blood Hg was associated with lower fetal RmtDNAcn (β = -0.002, 95%CI: -0.004, -0.000). Neither maternal blood Hg nor PUFA status was associated with fetal RmtDNAcn. CONCLUSIONS: Our findings suggest that MeHg and PUFA may influence mitochondrial homeostasis although the magnitude of these associations are small. Future studies should confirm the findings and explore the underlying mechanisms.
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