Environmental Exposures in the Etiology of Abortion: Placental Toxic and Trace Element Levels

Abstract

Purpose Intensive research has been conducted on the effects of toxic and trace elements on pregnancy. Previous studies indicated a possible relationship between placental levels of these elements and first-trimester abortion; however, their effects on the further gestational weeks are not clear. This study aimed to investigate the effect of changes in the levels of placental trace and toxic elements on second-trimester abortion.

Methods The patient group consisted of 30 women with missed abortion. The control group comprised 60 healthy term and singleton pregnant women who gave birth. Placental samples were obtained from the patients and the healthy controls, and the concentrations of placental elements were measured using inductively coupled plasma mass spectrometry.

Results In the abortion group, placental arsenic, cadmium, mercury, lead, antimony, tin, cobalt, manganese, and selenium levels were significantly higher than those of the control group (p<0.05). Antimony was determined as an independent predictor with an odds ratio of 6.1 in toxic elements (p=0.025), and selenium was determined as an independent predictor with an odds ratio of 2.3 in trace elements (p=0.015).

Conclusion The changes in trace element and toxic element levels, especially an increase in antimony and selenium, in placental tissue due to environmental exposure may play an important role in second-trimester abortion.

Key words

second-trimester abortions - heavy metal - trace element - toxic element - environmental exposure

Publication History

Received: 07 July 2020

Accepted: 06 September 2020

Article published online:
15 October 2020

• References

• 1 Jaslow CR, Carney JL, Kutteh WH. Diagnostic factors identified in 1020 women with two versus three or more recurrent pregnancy losses. Fertil Steril 2010; 93: 1234-1243
• 2 Zhang X. Practical Obstetrics and Gynecology. 2^nd ed. Beijing: People’s Medical Publishing House. 2003
• 3 Rouse CE, Eckert LO, Babarinsa I. et al. Spontaneous abortion and ectopic pregnancy: Case definition & guidelines for data collection, analysis, and presentation of maternal immunization safety data. Vaccine 2017; 35: 6563-6574
• 4 The American College Of Obstetricians And Gynecologists Practice Bulletin Early pregnancy loss. Obstet Gynecol 2015; 125: 1258-1267
• 5 Alijotas-Reig J, Garrido-Gimenez C. Current concepts and new trends in the diagnosis and management of recurrent miscarriage. Obstet Gynecol Surv 2013; 68: 445-466
• 6 Morales C, Sanchez A, Bruguera J. et al. Cytogenetic study of spontaneous abortions using semi-direct analysis of chorionic villi samples detects the broadest spectrum of chromosome abnormalities. Am J Med Genet A 2008; 146a: 66-70
• 7 Askerov R. Embryoscopic diagnostics of endometrial defects in missed abortion after IVF. Gynecol Endocrinol 2016; 32: 62-63
• 8 Martínez-Ruiz A, Sarabia-Meseguer MD, Pérez-Fornieles J. et al. Placental growth factor, soluble fms-like tyrosine kinase 1 and progesterone as diagnostic biomarkers for ectopic pregnancy and missed abortion. Clin Chem 2014; 47: 844-847
• 9 Chen M, Fan Z, Zhao F. et al. Occurrence and maternal transfer of chlorinated bisphenol A and nonylphenol in pregnant women and their matching embryos. Environ Sci Technol 2015; 50: 970-977
• 10 Zhao R, Wu Y, Zhao F. et al. The risk of missed abortion associated with the levels of tobacco, heavy metals and phthalate in hair of pregnant woman: A case control study in chinese women. Medicine 2017; 96: e9388
• 11 Al-Saleh I, Shinwari N, Mashhour A. et al. Heavy metals (lead, cadmium and mercury) in maternal, cord blood and placenta of healthy women. Int J Hyg Environ Health 2011; 214: 79-101
• 12 Wells PG, Lee CJ, McCallum GP. et al. Receptor-and reactive intermediate-mediated mechanisms of teratogenesis. Handb Exp Pharmacol 2010; 131-162
• 13 Caserta D, Graziano A, Monte GL. et al. Heavy metals and placental fetal-maternal barrier: a mini-review on the major concerns. Eur Rev Med Pharmacol Sci 2013; 17: 2198-2206
• 14 Iyengar G, Rapp A. Human placenta as a ‘dual’ biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 3: Toxic trace elements in placenta and placenta as a biomarker for these elements. Sci Total Environ 2001; 280: 221-238
• 15 Ahmad SA, Sayed M, Barua S. et al. Arsenic in drinking water and pregnancy outcomes. Environ Health Perspect 2001; 109: 629-631
• 16 Milton AH, Smith W, Rahman B. et al. Chronic arsenic exposure and adverse pregnancy outcomes in Bangladesh. Epidemiology 2005; 16: 82-86
• 17 Bellinger D, Leviton A, Rabinowitz M. et al. Weight gain and maturity in fetuses exposed to low levels of lead. Environ Res 1991; 54: 151-158
• 18 Tabacova S, Balabaeva L. Environmental pollutants in relation to complications of pregnancy. Environ Health Perspect 1993; 101: 27-31
• 19 Reddy YSYA, Ramalaksmi BA. et al. Lead and trace element levels in placenta, maternal and cord blood: a cross-sectional pilot study. J Obstet Gynaecol Res 2014; 40: 2184-2190
• 20 Gemzell-Danielsson K, Ho PC, Gomez Ponce de León R. et al. Misoprostol to treat missed abortion in the first trimester. Int J Gynaecol Obstet 2007; 99: 182-185
• 21 Aliyev V, Kayaalti Z, Kaplan B. et al. Effect of GST polymorphisms on As levels of placental and maternal biological samples. Toxicol Lett 2012; 211: 67
• 22 Faul F, Erdfelder E, Buchner A. et al. Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses. Behav Res Methods 2009; 41: 1149-1160
• 23 Liu Z, Lin Y, Tian X. et al. Association between maternal aluminum exposure and the risk of congenital heart defects in offspring. Birth Defects Res A Clin Mol Teratol 2016; 106: 95-103
• 24 Quig D. Cysteine metabolism and metal toxicity. Altern Med Rev 1998; 3: 262-270
• 25 Karakis I, Sarov B, Landau D. et al. Association between prenatal exposure to metals and neonatal morbidity. J Toxicol Environ Health A 2014; 77: 1281-1284
• 26 Shimada A, Yamamoto E, Morita T. et al. Ultrastructural demonstration of mercury granules in the placenta of metallothionein-null pregnant mice after exposure to mercury vapor. Toxicol Pathol 2004; 32: 519-526
• 27 Ma H, Li H, Wang J. et al. Expression and significance of metallothionein in the placenta of women with low level lead exposure during pregnancy. Zhonghua Fu Chan Ke Za Zhi 2006; 41: 676-679
• 28 Kippler M, Hoque AW, Raqib R. et al. Accumulation of cadmium in human placenta interacts with the transport of micronutrients to the fetus. Toxicol Lett 2010; 192: 162-168
• 29 García-Esquinas E, Pérez-Gómez B, Fernández-Navarro P. et al. Lead, mercury and cadmium in umbilical cord blood and its association with parental epidemiological variables and birth factors. BMC Public Health 2013; 13: 841
• 30 European Food Safety Authority. Scientific opinion of the panel on contaminants in the food chain on a request from the European Commission on cadmium in food. EFSA J 2009; 980: 1-139
• 31 Kordas K, Lonnerdal B, Stoltzfus RJ. Interactions between nutrition and environmental exposures: Effects on health outcomes in women and children. J Nutr 2007; 137: 2794-2797
• 32 Engström KS, Nermell B, Concha G. et al. Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions. Mutat Res 2009; 667: 4-14
• 33 Vahter M. Effects of arsenic on maternal and fetal health. Annu Rev Nutr 2009; 29: 381-399
• 34 Von Ehrenstein O, Guha Mazumder D, Hira-Smith M. et al. Pregnancy outcomes, infant mortality, and arsenic in drinking water in West Bengal, India. Am J Epidemiol 2006; 163: 662-669
• 35 Kannan K, Senthilkumar K, Giesy JP. Occurrence of butyltin compounds in human blood. Environ Sci Technol 1999; 33: 1776-1779
• 36 Rantakokko P, Turunen A, Verkasalo PK. et al. Blood levels of organotin compounds and their relation to fish consumption in Finland. Sci Total Environ 2008; 399: 90-95
• 37 Lo S, Allera A, Albers P. et al. Dithioerythritol (DTE) prevents inhibitory effects of triphenyltin (TPT) on the key enzymes of the human sex steroid hormone metabolism. J Steroid Biochem 2003; 84: 569-576
• 38 Nielsen JB, Strand J. Butyltin compounds in human liver. Environ Res 2002; 88: 129-133
• 39 Dobson S, Howe PD, Floyd P, World Health Organization & International Programme on Chemical Safety. Mono-and disubstituted methyltin, butyltin, and octyltin compounds. 2006. https://apps.who.int/iris/handle/10665/43549
• 40 Abadin H, Ashizawa A, Stevens Y. et al. Agency for Toxic Substances And Disease Registry (ATSDR) Toxicological Profiles. Toxicological Profile for Lead. Atlanta (GA): Agency for Toxic Substances and Disease Registry (US); 2007
• 41 Cooke GM, Forsyth DS, Bondy GS. et al. Organotin speciation and tissue distribution in rat dams, fetuses, and neonates following oral administration of tributyltin chloride. J Toxicol Environ Health A 2008; 71: 384-395
• 42 Volonakis G, Filip MR, Haghighirad AA. et al. Lead-free halide double perovskites via heterovalent substitution of noble metals. J Phys Chem Lett 2016; 7: 1254-1259
• 43 Choe S-Y, Kim S-J, Kim H-G. et al. Evaluation of estrogenicity of major heavy metals. Sci Total Environ 2003; 312: 15-21
• 44 Zhang G, Wang X, Zhang X. et al. Antimony in urine during early pregnancy correlates with increased risk of gestational diabetes mellitus: a prospective cohort study. Environ Int 2019; 123: 164-170
• 45 Amatu A, Imberti R Oxidative stress in applied basic research and clinical practice-studies on experimental models. Eur J Histochem 2012; br9-br9
• 46 Yiyenoğlu ÖB, Uğur MG, Özcan HÇ. et al. Assessment of oxidative stress markers in recurrent pregnancy loss: A prospective study. Arch Gynecol Obstet 2014; 289: 1337-1340
• 47 Chu FF, Esworthy RS, Doroshow JH. et al. Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents. Blood 1992; 79: 3233-3238
• 48 Ajayi O, Charles-Davies M, Arinola O. Progesterone, selected heavy metals and micronutrients in pregnant Nigerian women with a history of recurrent spontaneous abortion. Afr Health Sci 2012; 12: 153-159
• 49 Rayman MP, Wijnen H, Vader H. et al. Maternal selenium status during early gestation and risk for preterm birth. CMAJ 2011; 183: 549-555
• 50 Kim J, Gibb H, Howe P. Concise International Chemical Assessment Document 69. Cobalt and Inorganic Cobalt Compounds. Geneva: World Health Organization; 2006
• 51 Liang C, Wang J, Xia X. et al. Serum cobalt status during pregnancy and the risks of pregnancy-induced hypertension syndrome: a prospective birth cohort study. J Trace Elem Med Bio 2018; 46: 39-45
• 52 Oyagbemi A, Omobowale T, Awoyomi O. et al. Cobalt chloride toxicity elicited hypertension and cardiac complication via induction of oxidative stress and upregulation of Cox-2/Bax signaling pathway. Hum Exp Toxicol 2019; 38: 519-532
• 53 Barrington J, Lindsay P, James D. et al. Selenium deficiency and miscarriage: a possible link?. BJOG 1996; 103: 130-132
• 54 Barrington JW, Taylor M, Smith S. et al. Selenium and recurrent miscarriage. J Obstet Gynaecol 1997; 17: 199-200
• 55 Zachara BA, Dobrzyński W, Trafikowska U. et al. Blood selenium and glutathione peroxidases in miscarriage. BJOG 2001; 108: 244-247
• 56 Nicoll A, Norman J, Macpherson A. et al. Association of reduced selenium status in the aetiology of recurrent miscarriage. BJOG 1999; 106: 1188-1191
• 57 Behne D, Wolters W. Selenium content and glutathione peroxidase activity in the plasma and erythrocytes of non-pregnant and pregnant women. Clin Chem Lab Med 1979; 17: 133-136
• 58 Perona G, Guidi G, Piga A. et al. Neonatal erythrocyte glutathione peroxidase deficiency as a consequence of selenium imbalance during pregnancy. Br J Haematol 1979; 42: 567-574
• 59 Winnefeld K, Dawczynski H, Bosseckert H. et al. Serum-and whole blood selenium in certain diseases. Trace Elem Med 1993; 10: 90-92
• 60 Al-Saleh I, Al-Rouqi R, Obsum CA. et al. Interaction between cadmium (Cd), selenium (Se) and oxidative stress biomarkers in healthy mothers and its impact on birth anthropometric measures. Int J Hyg Envır Health 2015; 218: 66-90
• 61 Alonso MJL, Barrera AB, de Juan JAC. et al. Selenium levels in related biological samples: human placenta, maternal and umbilical cord blood, hair and nails. J Trace Elem Med Bio 2005; 19: 49-54
• 62 Klapec T, Ćavar S, Kasač Z. et al. Selenium in placenta predicts birth weight in normal but not intrauterine growth restriction pregnancy. J Trace Elem Med Bio 2008; 22: 54-58
• 63 Zadrożna M, Gawlik M, Nowak B. et al. Antioxidants activities and concentration of selenium, zinc and copper in preterm and IUGR human placentas. J Trace Elem Med Bio 2009; 23: 144-148
• 64 de Oliveira ACM, Santos AA, Bezerra AR. et al. Intake of antioxidant nutrients and coefficients of variation in pregnant women with preeclampsia. Revista Portuguesa de Cardiologia (English Edition) 2016; 35: 469-476
• 65 Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med 2005; 26: 353-362
• 66 Bjørklund G, Chartrand MS, Aaseth J. Manganese exposure and neurotoxic effects in children. Environ Res 2017; 155: 380-384
• 67 Bowler RM, Kornblith ES, Gocheva VV. et al. Environmental exposure to manganese in air: associations with cognitive functions. Neurotoxicology 2015; 49: 139-148
• 68 Menezes-Filho JA, Bouchard M, Sarcinelli PdN. et al. Manganese exposure and the neuropsychological effect on children and adolescents: a review. Rev Panam Salud Publica 2009; 26: 541-548
• 69 Sanders AP, Henn BC, Wright RO. Perinatal and childhood exposure to cadmium, manganese, and metal mixtures and effects on cognition and behavior: a review of recent literature. Curr Environ Health Rep 2015; 2: 284-294
• 70 Myatt L, Cui X. Oxidative stress in the placenta. Histochem Cell Biol 2004; 122: 369-382
• 71 Yazbeck C, Moreau T, Sahuquillo J. et al. Effect of maternal manganese blood levels on erythrocyte calcium-pump activity in newborns. Sci Total Environ 2006; 354: 28-34
• 72 Belkacemi L, Bédard I, Simoneau L. et al. Calcium channels, transporters and exchangers in placenta: a review. Cell Calcium 2005; 37: 1-8
• 73 Casart Y, Proverbio T, Marín R. et al. Ca-ATPase of human syncytiotrophoblast basal plasma membranes. Arch Physiol Biochem 2000; 108: 380-384
• 74 Lafond J, Simoneau L. Calcium homeostasis in human placenta: role of calcium-handling proteins. Int Rev Cytol 2006; 250: 109-174
• 75 Finley JW, Penland JG, Pettit RE. et al. Dietary manganese intake and type of lipid do not affect clinical or neuropsychological measures in healthy young women. J Nutr 2003; 133: 2849-2856