Timing of prenatal phthalate exposure in relation to genital endpoints in male newborns

the TIDES Study Team

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of androgen action in utero, may be shortened by prenatal exposure to certain phthalates, including diethylhexyl phthalate (DEHP), but no human study has investigated the importance of exposure timing in these associations. The aim of this study was to examine the significance of exposure timing on the action of prenatal phthalates in particular DEHP, on male infant penile size and AGD. In The Infant Development and the Environment Study (TIDES) we measured penile width (PW) as well as anoscrotal distance (AGDAS) and anopenile distance (AGPAP) in newborn males. We modeled these endpoints in relation to phthalate metabolite concentrations in maternal urine samples collected in each trimester (T1, T2, and T3) in a subset of TIDES mothers (N = 168). PW was inversely associated with T2 oxidized DEHP metabolites, mono-2-ethyl-5-oxohexyl (MEOHP, β=−0.48; 95% confidence interval, −0.93, −0.02), MEHHP (−0.48; −0.92, −0.05), mono-2-ethyl-5-carboxypentyl (MECPP, −0.51; −1.01, −0.004), although no appreciable associations were seen between PW and T1 and T3 DEHP metabolite concentrations in this subset. Concentrations of DEHP metabolites in T1 urine samples were inversely related to male AGD. For example, in T1 samples in this subset of women mono-2-ethyl-5-hydroxyhexyl (MEHHP) was inversely associated with male AGDAP (β = −1.73; 95% confidence interval, −3.45, 0.0004). However, no appreciable associations were seen between AGD measures and any DEHP metabolite in T2 and T3 samples. These data suggest that DEHP exposure is inversely associated with AGD and PW, with PW primarily associated with T2 exposure and AGD associations seen only for T1 exposure, but no associations were found between T3 DEHP metabolites and any of these genital endpoints. These findings are consistent with data on critical windows in rodent studies, supporting the biological plausibility of these associations in humans.

Original languageEnglish (US)
Pages (from-to)585-593
Number of pages9
JournalAndrology
Volume4
Issue number4
DOIs
StatePublished - Jul 1 2016

Fingerprint

Diethylhexyl Phthalate
Newborn Infant
Child Development
Mothers
Urine
Confidence Intervals
phthalic acid
Androgens
Rodentia

Keywords

  • fetal development
  • genital
  • phthalates
  • prenatal
  • timing

Cite this

Timing of prenatal phthalate exposure in relation to genital endpoints in male newborns. / the TIDES Study Team.

In: Andrology, Vol. 4, No. 4, 01.07.2016, p. 585-593.

Research output: Contribution to journalArticle

the TIDES Study Team. / Timing of prenatal phthalate exposure in relation to genital endpoints in male newborns. In: Andrology. 2016 ; Vol. 4, No. 4. pp. 585-593.
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abstract = "Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of androgen action in utero, may be shortened by prenatal exposure to certain phthalates, including diethylhexyl phthalate (DEHP), but no human study has investigated the importance of exposure timing in these associations. The aim of this study was to examine the significance of exposure timing on the action of prenatal phthalates in particular DEHP, on male infant penile size and AGD. In The Infant Development and the Environment Study (TIDES) we measured penile width (PW) as well as anoscrotal distance (AGDAS) and anopenile distance (AGPAP) in newborn males. We modeled these endpoints in relation to phthalate metabolite concentrations in maternal urine samples collected in each trimester (T1, T2, and T3) in a subset of TIDES mothers (N = 168). PW was inversely associated with T2 oxidized DEHP metabolites, mono-2-ethyl-5-oxohexyl (MEOHP, β=−0.48; 95{\%} confidence interval, −0.93, −0.02), MEHHP (−0.48; −0.92, −0.05), mono-2-ethyl-5-carboxypentyl (MECPP, −0.51; −1.01, −0.004), although no appreciable associations were seen between PW and T1 and T3 DEHP metabolite concentrations in this subset. Concentrations of DEHP metabolites in T1 urine samples were inversely related to male AGD. For example, in T1 samples in this subset of women mono-2-ethyl-5-hydroxyhexyl (MEHHP) was inversely associated with male AGDAP (β = −1.73; 95{\%} confidence interval, −3.45, 0.0004). However, no appreciable associations were seen between AGD measures and any DEHP metabolite in T2 and T3 samples. These data suggest that DEHP exposure is inversely associated with AGD and PW, with PW primarily associated with T2 exposure and AGD associations seen only for T1 exposure, but no associations were found between T3 DEHP metabolites and any of these genital endpoints. These findings are consistent with data on critical windows in rodent studies, supporting the biological plausibility of these associations in humans.",
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