Reproductive Toxicology 61 (2016) 142–150 Contents lists available at ScienceDirect Reproductive Toxicology j ourna l ho me pa g e: www.elsevier.com/locate/reprotox Follicular fluid and urinary concentrations of phthalate metabolites among infertile women and associations with in vitro fertilization parameters Yao-Yao Du a , Yue-Li Fang a , Yi-Xin Wang b,c , Qiang Zeng b,c , Na Guo a , Hua Zhao a , Yu-Feng Li a,∗ a Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China b Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China c Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China a r t i c l e i n f o Article history: Received 23 September 2015 Received in revised form 27 March 2016 Accepted 7 April 2016 Available online 8 April 2016 Keywords: Phthalates Follicular fluid IVF parameters Female reproduction Endocrine disruptors a b s t r a c t Evidence from toxicological studies has demonstrated that phthalates can lead to reduced fertility through effects on folliculogenesis, oocyte maturation and embryonic development, but human data are limited. Concentrations of eight phthalate metabolites in 110 follicular fluid (FF) and urine samples collected from 112 women attending an infertility clinic in Wuhan, China were quantified, and corre- lations between paired matrices were explored. Associations between metabolite concentrations and in vitro fertilization (IVF) parameters were evaluated with multivariable models. Six metabolites were detected in >72.73% of the FF samples. MEHP and MBP were the dominant metabolites with a median level of 2.80 and 2.05 ng/mL, respectively. Significant correlations between the two matrices, urine and FF, were found for MEP (rs = 0.44), and MBP (rs = 0.22). FF and urinary metabolite concentrations were not associated with any IVF parameters. However, given the prevalence of phthalates exposure, further work is needed to elucidate the potential hazard on female reproduction. © 2016 Elsevier Inc. All rights reserved. 1. Introduction Phthalates are a class of man-made industrial chemicals which have been ubiquitously applied to manufacture polyvinyl chloride products, such as construction materials, food packaging and chil- dren’s toys, mainly based on their ability to impart flexibility. They are also commonly used as solvents in cosmetics and personal care Abbreviations: AFC, antral follicle count; BMI, body mass index; DEHP, di(2-ethylhexyl) phthalate; EDCs, endocrine-disrupting chemicals; E2, estradiol; FF, follicular fluid; FSH, follicle-stimulating hormone; HCG, human chorionic gonadotropin; ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilization; LOD, the limits of detection; MBP, monobutyl phthalate; MBzP, monobenzyl phtha- late; MEP, monoethyl phthalate; MEHP, mono(2-ethylhexyl) phthalate; MEHHP, mono(2-ethyl-5-hydroxyhexyl) phthalate; MEOHP, mono(2-ethyl-5-oxohexyl) phthalate; MMP, monomethyl phthalate; MOP, mono-n-octyl phthalate; %MEHP, the percentage of DEHP metabolites excreted as MEHP; 2PN, two pronuclei. ∗ Corresponding author at: Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. E-mail addresses: yufengli64@163.com, yufengli64@tjh.tjmu.edu.cn (Y.-F. Li). products, or as excipients, such as coatings of medications and dietary supplements [1–3]. Owing to the extensive use of phtha- lates, as well as their non-covalent conjugation with the products, the general population has been pervasively exposed to these com- pounds [1]. Once the phthalates enter the human body via various routes, primarily through ingestion, they can interfere with the endocrine systems, thus so called “endocrine-disrupting chemi- cals (EDCs)” [1,4]. To date, detectable levels of phthalates and their metabolites have been found in a wide range of biological fluids including human urine, serum, semen, amniotic fluid, umbilical cord blood and breast milk [5–8]. Prevalent exposure to phthalates has aroused growing pub- lic health concern based on their endocrine-disrupting potency. The adverse effects of phthalates on male fertility have been well documented and extensively studied[9]. In females, on the other hand, the influence of phthalates on ovarian and repro- ductive functions remains not well understood. However, there is accumulated evidence from experimental animal studies sug- gesting that phthalates exert reproductive toxicity by targeting the ovary [10,11]. Exposure to phthalates has been demonstrated http://dx.doi.org/10.1016/j.reprotox.2016.04.005 0890-6238/© 2016 Elsevier Inc. All rights reserved.