Maternal urinary phthalates and sex-specific placental mRNA levels in an urban birth cohort

Environmental Health

Research

Paige L. Williams¹  Robin M. Whyatt²  Jessie P. Buckley³  Yaqi Zhao⁴  Myoung Keun Lee⁴  Jennifer J. Adibi⁵  Allan C. Just⁶  Hari K. Bhat⁷ 

[1] Department of Biostatistics, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, Building I, Room 415, 02115, Boston, MA, USA;Department of Environmental Health Sciences, Mailman School of Public Health, 722 W 168th Street, 10032, New York, NY, USA;Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, 21205, Baltimore, MD, USA;Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 Desoto Street, Parran Hall 5132, 15261, Pittsburgh, PA, USA;Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 Desoto Street, Parran Hall 5132, 15261, Pittsburgh, PA, USA;Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, USA;Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, Box 1057, One Gustave L. Levy Place, 10029, New York, NY, USA;Division of Pharmacology and Toxicology, UMKC School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, HSB 5251, 64108, Kansas City, MO, USA;

关键词: Placenta;    Phthalates;    mRNA;    Sex difference;    CGA;    Correlated vector;   

DOI  :  10.1186/s12940-017-0241-5

 received in 2016-08-24, accepted in 2017-03-23,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundPrenatal urinary concentrations of phthalates in women participants in an urban birth cohort were associated with outcomes in their children related to neurodevelopment, autoimmune disease risk, and fat mass at 3,5,7, and 8 years of life. Placental biomarkers and outcomes at birth may offer biologic insight into these associations. This is the first study to address these associations with candidate genes from the phthalate and placenta literature, accounting for sex differences, and using absolute quantitation methods for mRNA levels.MethodsWe measured candidate mRNAs in 180 placentas sampled at birth (HSD17B1, AHR, CGA, CYP19A1, SLC27A4, PTGS2, PPARG, CYP11A1) by quantitative PCR and an absolute standard curve. We estimated associations of loge mRNA with quartiles of urinary phthalate monoesters using linear mixed models. Phthalate metabolites (N = 358) and mRNAs (N = 180) were transformed to a z-score and modeled as independent, correlated vectors in relation to large for gestational age (LGA) and gestational diabetes mellitus (GDM).ResultsCGA was associated with 4 out of 6 urinary phthalates. CGA was 2.0 loge units lower at the 3rd vs. 1st quartile of mono-n-butyl phthalate (MnBP) (95% confidence interval (CI): −3.5, −0.5) in male placentas, but 0.6 loge units higher (95% CI: −0.8, 1.9) in female placentas (sex interaction p = 0.01). There was an inverse association of MnBP with PPARG in male placentas (−1.1 loge units at highest vs. lowest quartile, 95% CI: −2.0, −0.1). CY19A1, CYP11A1, CGA were associated with one or more of the following in a sex-specific manner: monobenzyl phthalate (MBzP), MnBP, mono-iso-butyl phthalate (MiBP). These 3 mRNAs were lower by 1.4-fold (95% CI: −2.4, -1.0) in male GDM placentas vs. female and non-GDM placentas (p-value for interaction = 0.04). The metabolites MnBP/MiBP were 16% higher (95% CI: 0, 22) in GDM pregnancies.ConclusionsPrenatal concentrations of certain phthalates and outcomes at birth were modestly associated with molecular changes in fetal placental tissue during pregnancy. Associations were stronger in male vs. female placentas, and associations with MnBP and MiBP were stronger than other metabolites. Placental mRNAs are being pursued further as potential mediators of exposure-induced risks to the health of the child.

【 授权许可】

CC BY   
© The Author(s). 2017