Hostname: page-component-8448b6f56d-qsmjn Total loading time: 0 Render date: 2024-04-23T20:28:57.680Z Has data issue: false hasContentIssue false
  • English
  • Français

Prenatal exposure to phthalates is associated with decreased anogenital distance and penile size in male newborns

Published online by Cambridge University Press:  18 April 2013

L. P. Bustamante-Montes ,
M. A. Hernández-Valero ,
D. Flores-Pimentel ,
M. García-Fábila ,
A. Amaya-Chávez ,
D. B. Barr  and
V. H. Borja-Aburto
L. P. Bustamante-Montes
Affiliation:
Unidad de Investigación con Enfoque Ecosistémico, Facultad de Medicina, Universidad Autónoma del Estado de México, Paseo Tollocan esq. Jesús Carranza, Toluca, C.P. 50180, Edo. de México, México
M. A. Hernández-Valero
Affiliation:
Department of Health Disparities Research, Center for Research on Minority Health, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA
D. Flores-Pimentel
Affiliation:
Centro de Investigación y Estudios Avanzados en Salud Pública, Facultad de Medicina, Universidad Autónoma del Estado de México, Paseo Tollocan esq. Jesús Carranza, Toluca, C.P. 50180, Edo. de México, México
M. García-Fábila
Affiliation:
Laboratorio de Toxicología, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Tollocan Esq. Colón s/n Col. Moderna de la Cruz, Toluca, C.P. 50180, Edo. de México, México
A. Amaya-Chávez
Affiliation:
Laboratorio de Análisis Instrumental, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Tollocán Esq. Colón s/n Col. Moderna de la Cruz, Toluca, C.P. 50180, Edo. de México, México
D. B. Barr
Affiliation:
Department of Environmental Health, Rollins School of Public Health, Emory University, Claudia N. Rollins Bldg. 2007, 1518 Clifton Road. Atlanta, GA 30322, USA
V. H. Borja-Aburto*
Affiliation:
Coordinación de Vigilancia Epidemiológica del Instituto Mexicano del Seguro Social (IMSS), Mier y Pesado no. 120 Col. del Valle, Deleg. Benito Juárez, C.P. 03100, México D.F., México
*
*Address for correspondence: Dr V. H. Borja-Aburto, Coordinación de Vigilancia Epidemiológica del Instituto Mexicano del Seguro Social (IMSS), Mier y Pesado no. 120 Col. del Valle, Deleg. Benito Juárez, C.P. 03100, México D.F., México. (Email victor.borja@imss.gob.mx)
Get access Rights & Permissions [Opens in a new window]

Abstract

Reproductive effects from phthalate exposure have been documented mostly in animal studies. This study explored the association between prenatal exposure to phthalate metabolites, anogenital distance and penile measurements in male newborns in Toluca, State of Mexico. A total of 174 pregnant women provided urine samples for phthalate analysis during their last prenatal visit, and the 73 who gave birth to male infants were included in the study. The 73 male newborns were weighed and measured using standardized methods after delivery. After adjusting for creatinine and supine length at birth, significant inverse associations were observed between an index of prenatal exposure to total phthalate exposure and the distance from the anus to anterior base of the penis (β = −0.191 mm per 1 μg/l, P = 0.037), penile width (β = −0.0414, P = 0.050) and stretched length (β = −0.2137, P = 0.034); prenatal exposure to mono-2-ethylhexyl phthalate exposure was associated with a reduction in the stretched length of the penis (β = −0.2604, P = 0.050). Human exposure to phthalates is a public health concern, and the system most vulnerable to its potential effects seems to be the immature male reproductive tract.

Keywords

phthalatesanogenital distancepenile measurementsprenatal exposure
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 4 , Issue 4 , August 2013 , pp. 300 - 306
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Schettler, T. Human exposure to phthalates via consumer products. Int J Androl. 2006; 29, 134–139.Google Scholar
2.Wormut, M. What are the sources of exposure to eight frequently used phthalic esters in Europeans? Risk Anal. 2006; 26, 803–824.Google Scholar
3.Hoppin, JA, Brock, JW, Davis, BJ, Baird, DD. Reproducibility of urinary phthalate metabolites in first morning urine samples. Environ Health Perspect. 2002; 110, 515–518.CrossRefGoogle ScholarPubMed
4.Hauser, R, Meeker, JD, Park, S, Silva, MJ, Calafat, AM. Temporal variability of urinary phthalate metabolite levels in men of reproductive age. Environ Health Perspect. 2004; 112, 1734–1740.Google Scholar
5.Teitelbaum, SL, Britton, JA, Calafat, AM, et al. Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States. Environ Res. 2008; 106, 257–269.Google Scholar
6.Masutomi, N, Shibutani, M, Takagi, H, et al. Impact of dietary exposure to methoxychlor, genistein, or diisononyl phthalate during the perinatal period on the development of the rat endocrine/reproductive systems in later life. Toxicology. 2002; 192, 149–170.Google Scholar
7.Parks, LG, Ostby, JS, Lambright, CR, et al. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci. 2000; 58, 339–349.CrossRefGoogle ScholarPubMed
8.Ema, M, Miyawaki, E. Adverse effects on development of the reproductive system in male offspring of rats given monobutyl phthalate, a metabolite of dibutyl phthalate during late pregnancy. Reprod Toxicol. 2001; 15, 189–194.Google Scholar
9.Gray, TJB, Beamand, JA. Effect of some phthalate esters and other testicular toxins on primary cultures of testicular cells. Food Chem Toxicol. 1984; 22, 123–131.Google Scholar
10.Nakahara, H, Shono, T, Suita, S. Effects of prenatal exposure to phthalate ester on both testicular descent and urogenital development in rats. Fukuoka Igaku Zasshi. 2003; 94, 331–337.Google Scholar
11.Swan, SH, Main, KM, Liu, F, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect. 2005; 113, 1056–1061.Google Scholar
12.Swan, SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ Res. 2008; 108, 177–184.Google Scholar
13.Suzuki, Y, Yoshinaga, J, Mizumoto, Y, Serizawa, S, Shiraishi, H. Foetal exposure to phthalate esters and anogenital distance in male newborns. Intl J Androl. 2012; 35, 236–244.CrossRefGoogle ScholarPubMed
14.Huang, PC, Kuo, PL, Chou, YY, Lin, SJ, Lee, CC. Association between prenatal exposure to phthalates and the health of newborns. Environ Int. 2009; 35, 14–20.Google Scholar
15.Salazar-Martínez, E, Romano-Riquer, P, Yáñez-Márquez, E, Longnecker, MP, Hernandez-Avila, M. Anogenital distance in human male and female newborns: a descriptive, cross-sectional study. Environ Health. 2005; 3, 8–13.CrossRefGoogle Scholar
16.Capurro, H, Konichezky, S, Fonseca, D, Caldeyro-Barcia, R. A simplified method for diagnosis of gestational age in the newborn infant. J Pediatr. 1978; 93, 120–122.CrossRefGoogle ScholarPubMed
17.Albro, PW, Jordan, ST, Schroeder, JL, Corbett, JT. Chromatographic separation and quantitative determination of metabolites of di-(2 ethylhexyl)phthalate from urine of laboratory animals. J Chromatogr. 1982; 244, 65–79.Google Scholar
18.Blount, BC, Milgram, KE, Silva, MJ, et al. Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS. Anal Chem. 2000; 72, 4127–4134.CrossRefGoogle ScholarPubMed
19.García, MA, Soberón, E, Cortez, M, Rodríguez, R, Herrera, JL. Métodos analíticos Guía de validación; Colegio Nacional de Químicos Farmacéuticos Biólogos A. C: México 2002.Google Scholar
20.Adibi, JJ, Whyatt, RM, Paige, LW, et al. Characterization of phthalate exposure among pregnant women assessed by repeat air and urine samples. Environ Health Perspect. 2008; 116, 467–473.Google Scholar
21.Svensson, K, Hernández-Ramírez, RU, Burguete-García, A, et al. Phthalate exposure associated with self-reported diabetes among Mexican women. Environ Res. 2011; 111, 792–796.Google Scholar
22.Romero-Franco, M, Hernández-Ramírez, RU, Calafat, AM, et al. Personal care product use and urinary levels of phthalate metabolites in Mexican women. Environ Int. 2011; 37, 867–871.Google Scholar
23.Romano-Riquer, SP, Hernández-Ávila, M, Gladen, BC, Cupul-Uicab, LA, Longnecker, MP. Reliability and determinants of anogenital distance and penis dimensions in male newborns from Chiapas, Mexico. Paediatr Perinat Epidemiol. 2007; 21, 219–228.Google Scholar
24.Fok, TF, Hon, KL, So, HK, et al. The Hong Kong Neonatal Measurements Working Group. Normative data of penile length for term Chinese newborns. Biol Neonate. 2005; 87, 242–245.CrossRefGoogle ScholarPubMed
25.Anigstein, CR. Longitud y diámetro del pene en niños de 0 a 14 años de edad. Arch Argent Pediatr. 2005; 103, 401–405.Google Scholar
26.Damon, V, Berlier, P, Durozier, B, Francois, R. Study of the dimensions of the penis from birth to adult age and as a function of testicular volume. Pediatrie. 1990; 45, 519–522.Google ScholarPubMed
27.Carmudan, AD, Oz, MO, Ilhan, MN, et al. Current stretched penile length: cross-sectional study of 1040 healthy Turkish children aged 0 to 5 years. Urology. 2007; 70, 572–575.Google Scholar
28.Al-Herbish, AS. Standard penile size for normal full term newborns in the Saudi population. Saudi Med J. 2002; 23, 314–316.Google Scholar
29.Fujieda, K, Matsuura, N. Growth and maturation in male genitalia from birth to adolescence II. Change of penile length. Pediatr Int. 1987; 29, 220–223.CrossRefGoogle ScholarPubMed
30.Lee, PA, Mazur, T, Danish, R, et al. Micropenis I. Criteria, etiologies and classification. Johns Hopkins Med J. 1980; 146, 156–163.Google ScholarPubMed
31.Anhalt, H, Neely, EK, Hintz, RL. Ambiguous genitalia. Pediatr Rev. 1996; 17, 213–220.CrossRefGoogle ScholarPubMed
32.Mendiola, J, Stahlnut, RW, Jorgensen, N, Liu, F, Swan, SH. Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York. Environ Health Pers. 2011; 119, 958–963.Google Scholar
33.Bowman, CJ, Barlow, NJ, Turner, KJ, Wallace, DG, Foster, PMD. Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rats. Toxicol Sci. 2003; 74, 393–406.Google Scholar
34.Ge, RS, Chen, GR, Tanrikut, C, Hardy, MP. Phthalate ester toxicity in Leydig cells: developmental timing and dosage considerations. Reprod Toxicol. 2007; 23, 366–373.CrossRefGoogle ScholarPubMed
35.Chen, GR, Dong, L, Ge, RS, Hardy, MP. Relationship between phthalates and testicular dysgenesis syndrome. Zhonghua Nan Ke Xue. 2007; 13, 195–200.Google Scholar
36.Welsh, M, Saunders, PTK, Fisken, M, et al. Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. J Clin Invest. 2008; 118, 1479–1490.Google Scholar
37.World Health Organization (WHO). 2003. Healthy environments for children. Retrieved August 10, 2010, from http://www.who.int/features/2003/04/eGoogle Scholar