Prenatal exposure to organochlorine pesticides and TSH status in newborns from Southern Spain
Research highlights
► Prenatal exposure to endocrine-disrupting chemicals may interfere with neonatal thyroid hormone status. ► Limited data is available on the relation between thyroid hormone levels and early exposure to organochlorine pesticides. ► Placental levels of endrin and endosulfan-sulfate were associated with neonatal TSH, although no consistent pattern emerged.
Introduction
Human exposure to environmental chemicals that disrupt endocrine homeostasis (endocrine disruptors [EDs]) has been mainly related to effects on sex hormones (estrogens and androgens). Thus, many organochlorine compounds (OCs) have been shown to display an estrogenic-like activity (DeCastro et al., 2006, Fernández et al., 2004). Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and dioxins/furans have also been demonstrated to influence thyroid hormone (TH) (thyroxine [T4], triiodothyronine [T3] and thyroid-stimulating hormone [TSH]) activity and metabolism in animal studies (Boas et al., 2006). With regard to OCPs, there are considerable animal data on the alteration of TH levels by exposure to p,p′-dichlorodiphenyldichloroethene (p,p′-DDE) and hexachlorobenzene (HCB) (ATSDR, 2002a, ATSDR, 2002b).
Thyroid disruption may be caused by various mechanisms, since different chemicals interfere with the hypothalamic–pituitary–thyroid axis at distinct levels. Several OCs are structurally similar to THs and therefore have the potential to bind to proteins and receptors that characteristically bind THs, producing complex effects on TH signaling (Zoeller, 2007). In addition, changes in serum TH concentrations can be caused by chemicals that inhibit TH synthesis, release and metabolism (Boas et al., 2006).
Several studies have investigated associations between OC exposure levels in human tissues and TH status in adults (Langer et al., 2006) and infants (Alvarez-Pedrerol et al., 2008, Asawasinsopon et al., 2006, Lopez-Espinosa et al., 2010, Ribas-Fitó et al., 2003, Takser et al., 2005), with no conclusive results (Boas et al., 2006, Maervoet et al., 2007). Discrepancies in these findings might result from differences in study populations, sample sizes, matrices for exposure measurement (e.g., maternal venous blood, cord blood, breast milk), specimen collection time points and/or isomers. Investigations into the effects of early OC exposure on human thyroid function have largely studied PCBs and dioxins (Maervoet et al., 2007, Wang et al., 2005). Recent studies suggested that p,p′-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane), p,p′-DDE, β-hexachlorocyclohexane (β-HCH) and HCB may also alter the thyroid system (Alvarez-Pedrerol et al., 2008, Alvarez-Pedrerol et al., 2009a, Alvarez-Pedrerol et al., 2009b, Takser et al., 2005). However, little is known about the disrupting potential of OCPs other than DDT, HCB, or HCH, e.g., mirex, aldrin and dieldrin (Asawasinsopon et al., 2006, Takser et al., 2005).
THs play an important role during early human development and it has been speculated that some of the neurotoxic and reproductive effects of early exposure to environmental EDs may result from disruption of the thyroid system (Williams, 2008). Thus, studies in infants have focused on the association between THs and adverse health effects such as low birth weight, growth retardation and altered psychomotor and cognitive functions (Alvarez-Pedrerol et al., 2009a, Alvarez-Pedrerol et al., 2009b, Freire et al., 2010b, Ribas-Fitó et al., 2007, Toft et al., 2004).
The production and use of most OCPs have been restricted or banned internationally since the 1970s, although some remain in legal use in various countries (Beard, 2006, PNA Convenio Estocolmo y Reglamento 850/2004., 2007). However, worldwide and intensive use of these compounds has led to widespread contamination of the environment and, due to their high persistence and bioaccumulation capacity, their presence is still detected in human tissues (Cerrillo et al., 2005, Lopez-Espinosa et al., 2007). Southern Spain has the largest area of intensive greenhouse agriculture in Europe and may constitute a special case of exposure to pesticides that have only recently been banned (in 2009), such as endosulfans (Cerrillo et al., 2005). In fact, Spain has been the main consumer of endosulfans in the European Union over the past few years (Endosulfan Preliminary Dossier, 2003).
Exposure to OCPs during human development may result in a permanent alteration of the endocrine system, and the fetus can be exposed to these compounds through the placenta. The present study aimed to investigate the relationship between cord blood TSH levels in a cohort of newborns from Granada, Southern Spain, and their prenatal exposure to a range of OCPs in placentas. This investigation is part of the INMA (INfancia y Medio Ambiente [Environment and Childhood]) Project, a prospective multi-center study in Spain (www.proyectoinma.org).
Section snippets
Subject recruitment
From 2000 to 2002, 700 eligible mother–son pairs registered at the San Cecilio University Hospital were enrolled at delivery, establishing the INMA-Granada male birth cohort, with the initial aim of investigating the relationship between chronic exposure to endocrine disrupting pesticides during pregnancy and urogenital malformations in newborn boys (Freire et al., 2010a, Lopez-Espinosa et al., 2007). Exclusion criteria were: maternal presence of serious chronic disease, such as diabetes,
Results
The mean age of the 220 mothers at delivery was 32 years (range = 16–46 years) and pre-pregnancy BMI was 24 kg/m2 (17–40 kg/m2). Around 24% of women were smokers, 9% consumed alcohol during pregnancy, 50% were primiparous, 16% had university education, and only 8% did not have a stable partner. The mean birth weight was 3335 g (2070–4590 g), and the mean duration of gestation was 39 weeks (32–42 weeks); 10% of the boys were small for gestational age (SGA). All cord blood TSH levels were within normal
Discussion
The relationship between exposure to placental OCPs and TSH levels was investigated in 220 male newborns from the general population. It was found that the risk of cord blood TSH ≥ 5 mU/L was higher in neonates prenatally exposed to greater concentrations of endrin but lower in those exposed to greater concentrations of endosulfan-sulfate. Marginally significant associations were found between higher TSH concentrations and higher p,p′-DDE and lower HCB. Exposure to OCPs during fetal development
Conclusions
This is the first report on the relationship between TSH status at birth and prenatal exposure to a wide range of OCPs as measured in the placenta. Although some associations were detected between OCP exposure and TSH cord blood levels, no clear pattern emerged on the influence of the compounds measured in placenta tissue on neonatal TH status. The impact of environmental chemicals on thyroid hormone levels and metabolism is a matter of growing concern, and further research is warranted to
Funding sources
This work was supported by the Consejería de Salud de la Junta de Andalucía [grant number P09-CTS-5488]; the Spanish Ministry of Health [grant number FIS07/0252]; and the European Commission [grant number CONTAMED-FP7-ENV-2007-1-212502 and EUS2008-03574].
Acknowledgments
The authors are grateful to Richard Davies for editorial assistance. The results would not have been achieved without the selfless collaboration of the study participants, the staff at the Department of Gynecology and Pediatrics of the San Cecilio University Hospital and at the Environmental Health Department of the Consejería de Salud de la Junta de Andalucía.
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