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, Bruce B Redmon, Shanna H. Swan

Research output: Contribution to journalArticle

21 Citations (Scopus)

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

Fingerprint

Chorionic Gonadotropin
First Pregnancy Trimester
Child Development
Newborn Infant
Sexual Development
Anal Canal
Second Pregnancy Trimester
phthalic acid
Serum
Prenatal Diagnosis
Gonadotropins
Sex Characteristics
Pregnant Women
Rodentia
Screening
Fetus
Mothers
Parturition

Cite this

Human chorionic gonadotropin partially mediates phthalate association with male and female anogenital distance. / Adibi, Jennifer J.; Lee, Myoung Keun; Naimi, Ashley I.; Barrett, Emily; Nguyen, Ruby H; Sathyanarayana, Sheela; Zhao, Yaqi; Thiet, Mari Paule; Redmon, Bruce B; Swan, Shanna H.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 9, 01.09.2015, p. E1216-E1224.

Research output: Contribution to journalArticle

Adibi, Jennifer J. ; Lee, Myoung Keun ; Naimi, Ashley I. ; Barrett, Emily ; Nguyen, Ruby H ; Sathyanarayana, Sheela ; Zhao, Yaqi ; Thiet, Mari Paule ; Redmon, Bruce B ; Swan, Shanna H. / Human chorionic gonadotropin partially mediates phthalate association with male and female anogenital distance. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 9. pp. E1216-E1224.
@article{1dce96c7344244cbb0aa99841600217a,
title = "Human chorionic gonadotropin partially mediates phthalate association with male and female anogenital distance",
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.",
author = "Adibi, {Jennifer J.} and Lee, {Myoung Keun} and Naimi, {Ashley I.} and Emily Barrett and Nguyen, {Ruby H} and Sheela Sathyanarayana and Yaqi Zhao and Thiet, {Mari Paule} and Redmon, {Bruce B} and Swan, {Shanna H.}",
year = "2015",
month = "9",
day = "1",
doi = "10.1210/jc.2015-2370",
language = "English (US)",
volume = "100",
pages = "E1216--E1224",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "9",

}

TY - JOUR

T1 - Human chorionic gonadotropin partially mediates phthalate association with male and female anogenital distance

AU - Adibi, Jennifer J.

AU - Lee, Myoung Keun

AU - Naimi, Ashley I.

AU - Barrett, Emily

AU - Nguyen, Ruby H

AU - Sathyanarayana, Sheela

AU - Zhao, Yaqi

AU - Thiet, Mari Paule

AU - Redmon, Bruce B

AU - Swan, Shanna H.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84941687236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941687236&partnerID=8YFLogxK

U2 - 10.1210/jc.2015-2370

DO - 10.1210/jc.2015-2370

M3 - Article

VL - 100

SP - E1216-E1224

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 9

ER -