PMID- 36174683
OWN - NLM
STAT- MEDLINE
DCOM- 20221123
LR  - 20221123
IS  - 1879-1026 (Electronic)
IS  - 0048-9697 (Linking)
VI  - 856
IP  - Pt 1
DP  - 2023 Jan 15
TI  - Prenatal exposure to organophosphate esters is associated with decreased 
      anogenital distance in offspring.
PG  - 159050
LID - S0048-9697(22)06149-6 [pii]
LID - 10.1016/j.scitotenv.2022.159050 [doi]
AB  - BACKGROUND: Evidence from in vitro and rodent studies suggests that 
      organophosphate esters (OPEs) may disrupt sex steroid hormone homeostasis, but no 
      human studies, to date, have examined the effects of in utero exposure to OPEs on 
      offspring reproductive development. OBJECTIVE: Anogenital distance (AGD) is a 
      sensitive biomarker of fetal hormonal milieu and has been used to assess 
      reproductive toxicity. We evaluated the longitudinal effects of prenatal exposure 
      to OPEs on the AGD of offspring from birth to 4 years. METHODS: Based on 
      Shanghai-Minhang Birth Cohort Study, pregnant women provided urine samples at a 
      gestational age of 12-16 weeks, which were analyzed for eight OPE metabolites. 
      AGD was measured in offspring at birth and 0.5, 1, and 4 years of age. We used 
      generalized estimating equations (GEE) and Bayesian kernel machine regression 
      (BKMR) models to estimate the associations of prenatal exposure to individual OPE 
      metabolites and OPE mixtures with AGD stratified by sex. RESULTS: A total of 733 
      mother-infant pairs were analyzed. Prenatal exposure to diphenyl phosphate and 
      bis-(2-ethylhexyl) phosphate was associated with decreased AGD in boys in GEE 
      models. Bis-(1-chloro-2-propyl) phosphate (BCIPP) showed a similar but marginally 
      significant effect. Prenatal exposure to most OPE metabolites was associated with 
      decreased AGD in girls, with the most profound association observed for bis 
      (2-butoxyethyl) phosphate (BBOEP) and alkyl-OPEs. The OPE mixture was also 
      inversely associated with AGD in both sexes. The single-exposure effects of BKMR 
      models were largely consistent with those observed in the GEE models. In 
      addition, alkyl-OPEs, particularly BBOEP, contributed the most to the decreased 
      AGD in girls, while BCIPP contributed the most to the decreased AGD in boys. 
      CONCLUSIONS: This study provides the first human evidence that prenatal exposure 
      to OPEs is associated with decreased AGD in offspring. The magnitude of these 
      effects may vary depending on the structure of OPEs.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Luan, Min
AU  - Luan M
AD  - NHC Key Lab. of Reproduction Regulation (Shanghai Institute for Biomedical and 
      Pharmaceutical Technologies), Shanghai, China.
FAU - Liang, Hong
AU  - Liang H
AD  - NHC Key Lab. of Reproduction Regulation (Shanghai Institute for Biomedical and 
      Pharmaceutical Technologies), Shanghai, China.
FAU - Chen, Yafei
AU  - Chen Y
AD  - NHC Key Lab. of Reproduction Regulation (Shanghai Institute for Biomedical and 
      Pharmaceutical Technologies), Shanghai, China.
FAU - Chen, Da
AU  - Chen D
AD  - School of Environment and Guangdong Key Laboratory of Environment Pollution and 
      Health, Jinan University, Guangzhou, China.
FAU - Ji, Honglei
AU  - Ji H
AD  - NHC Key Lab. of Reproduction Regulation (Shanghai Institute for Biomedical and 
      Pharmaceutical Technologies), Shanghai, China.
FAU - Chen, Hexia
AU  - Chen H
AD  - School of Environment and Guangdong Key Laboratory of Environment Pollution and 
      Health, Jinan University, Guangzhou, China.
FAU - Miao, Maohua
AU  - Miao M
AD  - NHC Key Lab. of Reproduction Regulation (Shanghai Institute for Biomedical and 
      Pharmaceutical Technologies), Shanghai, China. Electronic address: 
      miaomaohua@163.com.
FAU - Yuan, Wei
AU  - Yuan W
AD  - NHC Key Lab. of Reproduction Regulation (Shanghai Institute for Biomedical and 
      Pharmaceutical Technologies), Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20220926
PL  - Netherlands
TA  - Sci Total Environ
JT  - The Science of the total environment
JID - 0330500
RN  - 0 (bis(2-butoxyethyl)phosphate)
RN  - 0 (bis(1-chloro-2-propyl)phosphate)
RN  - 0 (Organophosphates)
RN  - 0 (Phosphates)
SB  - IM
MH  - Male
MH  - Infant
MH  - Infant, Newborn
MH  - Humans
MH  - Female
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects/chemically induced
MH  - Cohort Studies
MH  - Bayes Theorem
MH  - China
MH  - Organophosphates/toxicity/urine
MH  - Phosphates
OTO - NOTNLM
OT  - Anogenital distance
OT  - Cohort study
OT  - Organophosphate esters
OT  - Prenatal exposure
OT  - Reproductive development
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/09/30 06:00
MHDA- 2022/11/24 06:00
CRDT- 2022/09/29 19:32
PHST- 2022/08/09 00:00 [received]
PHST- 2022/09/22 00:00 [revised]
PHST- 2022/09/22 00:00 [accepted]
PHST- 2022/09/30 06:00 [pubmed]
PHST- 2022/11/24 06:00 [medline]
PHST- 2022/09/29 19:32 [entrez]
AID - S0048-9697(22)06149-6 [pii]
AID - 10.1016/j.scitotenv.2022.159050 [doi]
PST - ppublish
SO  - Sci Total Environ. 2023 Jan 15;856(Pt 1):159050. doi: 
      10.1016/j.scitotenv.2022.159050. Epub 2022 Sep 26.