Human chorionic gonadotropin partially mediates phthalate association with male and female anogenital distance

Jennifer J. Adibi, Myoung Keun Lee, Ashley I. Naimi, Emily Barrett, Ruby H. Nguyen, Sheela Sathyanarayana, Yaqi Zhao, Mari Paule Thiet, J. Bruce Redmon, Shanna H. Swan

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Context: Prenatal exposure to phthalates disrupts male sex development in rodents. In humans, the placental glycoproteinhormonehumanchorionic gonadotropin (hCG) is required formaledevelopment, and may be a target of phthalate exposure. Objective: This study aimed to test the hypothesis that phthalates disrupt placental hCG differentially in males and females with consequences for sexually dimorphic genital development. Design: The Infant Development and Environment Study (TIDES) is a prospective birth cohort. Pregnant women were enrolled from 2010-2012 at four university hospitals. Participants: Participants were TIDES subjects (n = 541) for whom genital and phthalate measurements were available and who underwent prenatal serum screening in the first or second trimester. MainOutcomeMeasures:OutcomesincludedhCGlevels in maternal serum in the firstandsecond trimestersand anogenital distance (AGD), which is the distance from the anus to the genitals in male and female neonates. Results: Higher first-trimester urinary mono-n-butyl phthalate (MnBP; P = .01), monobenzyl phthalate (MBzP; P = .03), and mono-carboxy-isooctyl phthalate (P < .01) were associated with higher first-trimester hCG in women carrying female fetuses, and lower hCG in women carrying males. First-trimester hCG was positively correlated with the AGD z score in female neonates, and inversely correlated in males (P=0.01).Wemeasured significant associations of MnBP(P<.01),MBzP(P=.02),andmono-2-ethylhexyl phthalate (MEHP; P<.01) with AGD, after adjusting for sex differences. Approximately 52% (MnBP) and 25%(MEHP) of this association in males, and78%in females (MBzP), could be attributed to the phthalate association with hCG. Conclusions:First-trimesterhCGlevels,normalizedbyfetalsex,mayreflectsexuallydimorphicactionofphthalates on placental function and on genital development.

Original languageEnglish (US)
Pages (from-to)E1216-E1224
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number9
DOIs
StatePublished - Sep 1 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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