Prenatal and peripubertal phthalates and bisphenol A in relation to sex hormones and puberty in boys
Introduction
Phthalates and bisphenol A (BPA) are high production chemicals used in a wide variety of consumer products. Ubiquity in the environment leads to human exposure via ingestion of contaminated food and drinking water, dermal absorption, and inhalation of contaminated air [1], [2]. Hence, phthalate metabolites and BPA are highly detectable in urine samples of men, women, and children worldwide [3], [4].
Both phthalates and BPA are classified as endocrine disruptors because of their ability to disrupt hormone action through anti-androgenic and estrogenic mechanisms, respectively [5]. A number of studies have examined the relationship between exposure to these compounds and sex hormone levels in adult males [6]. Recently the effects in pregnant women have received increased attention because of the potential consequences on child development [7]. However, few studies have measured associations in children, and none have examined the impact of prenatal exposures on sex hormone levels and timing of puberty. Therefore, our objective was to examine the association between prenatal exposure to phthalate metabolites and BPA, measured in maternal urine collected during the 3rd trimester of pregnancy, and sex hormone levels as well as the development of secondary sex characteristics in boys aged 8–14 years. Additionally, we examined the cross-sectional associations between exposures measured in urine from boys at the same time as outcomes were assessed, which has not been done previously for BPA.
Section snippets
Study population
Participants were selected from three cohorts of pregnant women originally recruited as part of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) project [8], [9], [10]. Recruitment differed slightly by cohort, however most of the study participants were recruited during 1st trimester prenatal visits at either maternity hospitals or the Mexican Institute of Social Security in Mexico City from 1994 to 2004 [9], [10]. Women were followed throughout pregnancy and participated
Results
Boys ranged in age from 8.10 to 14.4 years at the time of Tanner stage/testicular volume assessment and sample collection. Prenatal and childhood exposure distributions have been previously presented on a subset of this population (N = 49 prenatal samples for boys, N = 53 childhood samples for boys) [10]. Levels were similar in our expanded population (Supplemental Tables 1 and 2). Spearman correlations between prenatal and childhood exposure levels were weak (R ≤ 0.25), as we reported previously [10]
Discussion
We examined associations between prenatal and childhood phthalate and BPA exposures and sex hormone levels and pubertal onset in male children from Mexico City. We found for the first time that prenatal exposure to phthalates as well as BPA may be linked to reduced odds of adrenarche and puberty, although associations with sex hormone levels were less clear. We further observed that while childhood exposure levels were more strongly associated with hormone levels, particularly SHBG, Total T,
Conclusions
Our study utilizes a longitudinal design to explore for the first time the relationship between prenatal exposure to phthalates or BPA and both sex hormone levels and odds of adrenarche and puberty in males during the peripubertal period. We observed that prenatal exposure to several phthalate metabolites was associated with reduced odds of adrenarche and pubarche and with slightly increased levels of SHBG in males ages 8–14. Additionally we observed in cross-sectional analysis that childhood
Conflict of interest
The authors declare that they have no conflicts of interest.
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Acknowledgements
The present study was supported by grants P20 ES018171, P01ES022844, and P30ES017885 from the National Institute of Environmental Health Sciences, National Institutes of Health and Grant RD83480001 from the US Environmental Protection Agency.
References (58)
Bisphenol A and human health: a review of the literature
Reprod Toxicol
(2013)- et al.
A review of dietary and non-dietary exposure to bisphenol-A
Food Chem Toxicol.
(2012) Exposure to environmental endocrine disrupting compounds and men's health
Maturitas
(2010)- et al.
Predictors of urinary bisphenol A and phthalate metabolite concentrations in Mexican children
Chemosphere
(2013) Bisphenol A and human health: a review of the literature
Reprod Toxicol
(2013)- et al.
Quantification of 22 phthalate metabolites in human urine
J Chromatogr B Analyt Technol Biomed Life Sci
(2007) Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans
Environ Res
(2008)- et al.
Pubertal staging in boys
J Pediatr
(1995) - et al.
isphenol-A acts as a potent estrogen via non-classical estrogen triggered pathways
Mol Cell Endocrinol
(2012) - et al.
Fetal testosterone insufficiency and abnormal proliferation of Leydig cells and gonocytes in rats exposed to di(n-butyl) phthalate
Reprod Toxicol
(2002)
Phthalates and other additives in plastics: human exposure and associated health outcomes
Philos Trans R Soc Lond B Biol Sci
Assessing exposure to phthalates – the human biomonitoring approach
Mol Nutr Food Res
Endocrine-disrupting chemicals and public health protection: a statement of principles from The Endocrine Society
Endocrinology
Phthalate exposure and reproductive hormone concentrations in pregnancy
Reproduction
Decrease in birth weight in relation to maternal bone-lead burden
Pediatrics
Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development
Environ Health Perspect
Phthalate exposure and children's health
Curr Opin Pediatr
Estimation of average concentration in the presence of nondetectable values
Appl Occup Environ Hyg
A critical evaluation of simple methods for the estimation of free testosterone in serum
J Clin Endocrinol Metab
Variations in the pattern of pubertal changes in boys
Arch Dis Child
Secondary sexual characteristics in boys: estimates from the national health and nutrition examination survey III, 1988–1994
Arch Pediatr Adolesc Med
The pubertal transition in 179 healthy Danish children: associations between pubarche, adrenarche, gonadarche, and body composition
Eur J Endocrinol
WHO Reference 2007: Growth reference data for 5–19 years
Association of blood lead levels with onset of puberty in Russian boys
Environ Health Perspect
Human ‘testicular dysgenesis syndrome’: a possible model using in-utero exposure of the rat to dibutyl phthalate
Hum Reprod
Altered gene profiles in fetal rat testes after in utero exposure to di(n-butyl) phthalate
Toxicol Sci
Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters
Int J Androl
Decrease in anogenital distance among male infants with prenatal phthalate exposure
Environ Health Perspect
Endocrine disruptors in the workplace, hair spray, folate supplementation, and risk of hypospadias: case–control study
Environ Health Perspect
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