Decrease in anogenital distance among male infants with prenatal phthalate exposure
- PMID:16079079
- PMCID: PMC1280349
- DOI: 10.1289/ehp.8100
Decrease in anogenital distance among male infants with prenatal phthalate exposure
Erratum in
- Environ Health Perspect. 2005 Sep;113(9):A583
Abstract
Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation to prenatal phthalate exposure in humans. A standardized measure of AGD was obtained in 134 boys 2-36 months of age. AGD was significantly correlated with penile volume (R = 0.27, p = 0.001) and the proportion of boys with incomplete testicular descent (R = 0.20, p = 0.02). We defined the anogenital index (AGI) as AGD divided by weight at examination [AGI = AGD/weight (mm/kg)] and calculated the age-adjusted AGI by regression analysis. We examined nine phthalate monoester metabolites, measured in prenatal urine samples, as predictors of age-adjusted AGI in regression and categorical analyses that included all participants with prenatal urine samples (n = 85). Urinary concentrations of four phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoisobutyl phthalate (MiBP)] were inversely related to AGI. After adjusting for age at examination, p-values for regression coefficients ranged from 0.007 to 0.097. Comparing boys with prenatal MBP concentration in the highest quartile with those in the lowest quartile, the odds ratio for a shorter than expected AGI was 10.2 (95% confidence interval, 2.5 to 42.2). The corresponding odds ratios for MEP, MBzP, and MiBP were 4.7, 3.8, and 9.1, respectively (all p-values < 0.05). We defined a summary phthalate score to quantify joint exposure to these four phthalate metabolites. The age-adjusted AGI decreased significantly with increasing phthalate score (p-value for slope = 0.009). The associations between male genital development and phthalate exposure seen here are consistent with the phthalate-related syndrome of incomplete virilization that has been reported in prenatally exposed rodents. The median concentrations of phthalate metabolites that are associated with short AGI and incomplete testicular descent are below those found in one-quarter of the female population of the United States, based on a nationwide sample. These data support the hypothesis that prenatal phthalate exposure at environmental levels can adversely affect male reproductive development in humans.
Figures
Comment in
- Phthalate exposure during pregnancy and lower anogenital index in boys: wider implications for the general population?Sharpe RM.Sharpe RM.Environ Health Perspect. 2005 Aug;113(8):A504-5. doi: 10.1289/ehp.113-a504.Environ Health Perspect. 2005.PMID:16079047Free PMC article.No abstract available.
- Validity of anogenital distance as a marker of in utero phthalate exposure.McEwen GN Jr, Renner G.McEwen GN Jr, et al.Environ Health Perspect. 2006 Jan;114(1):A19-20; author reply A20-1. doi: 10.1289/ehp.114-1332693.Environ Health Perspect. 2006.PMID:16393642Free PMC article.No abstract available.
- Prenatal phthalate exposure and anogenital distance in male infants.Swan SH.Swan SH.Environ Health Perspect. 2006 Feb;114(2):A88-9. doi: 10.1289/ehp.114-a88b.Environ Health Perspect. 2006.PMID:16451842Free PMC article.No abstract available.
Similar articles
- First trimester phthalate exposure and anogenital distance in newborns.Swan SH, Sathyanarayana S, Barrett ES, Janssen S, Liu F, Nguyen RH, Redmon JB; TIDES Study Team.Swan SH, et al.Hum Reprod. 2015 Apr;30(4):963-72. doi: 10.1093/humrep/deu363. Epub 2015 Feb 18.Hum Reprod. 2015.PMID:25697839Free PMC article.
- Possible impact of phthalates on infant reproductive health.Lottrup G, Andersson AM, Leffers H, Mortensen GK, Toppari J, Skakkebaek NE, Main KM.Lottrup G, et al.Int J Androl. 2006 Feb;29(1):172-80; discussion 181-5. doi: 10.1111/j.1365-2605.2005.00642.x.Int J Androl. 2006.PMID:16466537Review.
- Prenatal Exposure to Phthalates and Anogenital Distance in Male Infants from a Low-Exposed Danish Cohort (2010-2012).Jensen TK, Frederiksen H, Kyhl HB, Lassen TH, Swan SH, Bornehag CG, Skakkebaek NE, Main KM, Lind DV, Husby S, Andersson AM.Jensen TK, et al.Environ Health Perspect. 2016 Jul;124(7):1107-13. doi: 10.1289/ehp.1509870. Epub 2015 Dec 15.Environ Health Perspect. 2016.PMID:26672060Free PMC article.
- Prenatal phthalate exposures and anogenital distance in Swedish boys.Bornehag CG, Carlstedt F, Jönsson BA, Lindh CH, Jensen TK, Bodin A, Jonsson C, Janson S, Swan SH.Bornehag CG, et al.Environ Health Perspect. 2015 Jan;123(1):101-7. doi: 10.1289/ehp.1408163. Epub 2014 Oct 29.Environ Health Perspect. 2015.PMID:25353625Free PMC article.
- Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters.Foster PM.Foster PM.Int J Androl. 2006 Feb;29(1):140-7; discussion 181-5. doi: 10.1111/j.1365-2605.2005.00563.x. Epub 2005 Aug 11.Int J Androl. 2006.PMID:16102138Review.
Cited by
- Short-Half-Life Chemicals: Maternal Exposure and Offspring Health Consequences-The Case of Synthetic Phenols, Parabens, and Phthalates.Rousseau-Ralliard D, Bozec J, Ouidir M, Jovanovic N, Gayrard V, Mellouk N, Dieudonné MN, Picard-Hagen N, Flores-Sanabria MJ, Jammes H, Philippat C, Couturier-Tarrade A.Rousseau-Ralliard D, et al.Toxics. 2024 Sep 29;12(10):710. doi: 10.3390/toxics12100710.Toxics. 2024.PMID:39453131Free PMC article.Review.
- Prenatal exposure to Di(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts gonadal function in male mice†.Barakat R, Lin PP, Bunnell M, Oh JE, Rattan S, Arnieri C, Flaws JA, Ko CJ.Barakat R, et al.Biol Reprod. 2024 May 9;110(5):1025-1037. doi: 10.1093/biolre/ioae029.Biol Reprod. 2024.PMID:38381622Free PMC article.
- Correlation of anogenital distance from childhood to age 9 years-a prospective population-based birth cohort-the Odense Child Cohort.Andreasen SM, Gehrt L, Hagen CP, Juul A, Mola G, Fischer MB, Andersen MS, Kristensen DM, Jensen TK.Andreasen SM, et al.Hum Reprod Open. 2024 Sep 9;2024(3):hoae050. doi: 10.1093/hropen/hoae050. eCollection 2024.Hum Reprod Open. 2024.PMID:39308771Free PMC article.
- Relationship of urinary phthalate metabolites with serum thyroid hormones in pregnant women and their newborns: a prospective birth cohort in Taiwan.Kuo FC, Su SW, Wu CF, Huang MC, Shiea J, Chen BH, Chen YL, Wu MT.Kuo FC, et al.PLoS One. 2015 Jun 4;10(6):e0123884. doi: 10.1371/journal.pone.0123884. eCollection 2015.PLoS One. 2015.PMID:26042594Free PMC article.Clinical Trial.
- Couples' urinary bisphenol A and phthalate metabolite concentrations and the secondary sex ratio.Bae J, Kim S, Kannan K, Buck Louis GM.Bae J, et al.Environ Res. 2015 Feb;137:450-7. doi: 10.1016/j.envres.2014.11.011. Epub 2015 Feb 9.Environ Res. 2015.PMID:25677702Free PMC article.
References
- Barlow NJ, Foster PM. Pathogenesis of male reproductive tract lesions from gestation through adulthood following in utero exposure to di(n-butyl) phthalate. Toxicol Pathol. 2003;31:397–410. - PubMed
- Barlow NJ, McIntyre BS, Foster PM. Male reproductive tract lesions at 6, 12, and 18 months of age following in utero exposure to di(n-butyl) phthalate. Toxicol Pathol. 2004;32:79–90. - PubMed
- Bowman CJ, Barlow NJ, Turner KJ, Wallace DG, Foster PM. Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat. Toxicol Sci. 2003;74:393–406. - PubMed
- Callegari C, Everett S, Ross M, Brasel JA. Anogenital ratio: measure of fetal virilization in premature and full-term newborn infants. J Pediatr. 1987;111:240–243. - PubMed
- CDC 2003. Second National Report on Human Exposure to Environmental Chemicals. Atlanta, GA:Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences.
Publication types
MeSH terms
Substances
Related information
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous