Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China

Environmental Pollution xxx (2016) 1e9

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Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China* Xiaolan Zhang a, Xiaojing Li a, Ye Jing a, Xiangming Fang b, Xinyu Zhang a, Bingli Lei a, Yingxin Yu a, * a b

Institute of Environmental Pollution and Health, School of Environment and Chemical Engineering, Shanghai University, Shanghai, 200444, PR China Shanghai Huangpu Maternity & Infant Health Hospital, Shanghai, 200020, PR China

a r t i c l e i n f o

a b s t r a c t

Article history: Received 12 October 2016 Received in revised form 17 December 2016 Accepted 17 December 2016 Available online xxx

Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a high-priority public health concern. However, maternal to fetal transplacental transfer of PAHs has not been systematically studied. To investigate the transplacental transfer of PAHs from mother to fetus and determine the influence of lipophilicity (octanol-water partition coefficient, KOW) on transfer process, in the present study, we measured the concentrations of 15 PAHs in 95 paired maternal and umbilical cord serum, and placenta samples (in total 285 samples) collected in Shanghai, China. The average concentration of total PAHs was the highest in maternal serums (1290 ng g
1 lipid), followed by umbilical cord serums (1150 ng g-1 lipid). The value was the lowest in placenta samples (673 ng g-1 lipid). Low molecular weight PAHs were the predominant compounds in the three matrices. Increases in fish and meat consumption did not lead to increases in maternal PAH levels, and no obvious gender differences in umbilical cord serums were observed. The widespread presence of PAHs in umbilical cord serums indicated the occurrence of transplacental transfer. The ratios of PAH concentrations in umbilical cord serum to those in maternal serum (F/M) and the concentrations in placenta to those in maternal serum (P/M) of paired samples were analyzed to characterize the transfer process of individual PAHs. Most F/M ratios on lipid basis were close to one (range: 0.79 to 1.36), which suggested that passive diffusion may control the transplacental transfer of PAHs from maternal serum to the fetal circulation. The P/M and F/M values calculated on lipid basis showed that PAHs with lower KOW were more likely to transfer from mother to fetus via the placenta. © 2016 Elsevier Ltd. All rights reserved.

Keywords: Maternal serum Placenta Polycyclic aromatic hydrocarbons Transplacental transfer Umbilical cord serum

1. Introduction Polycyclic aromatic hydrocarbons (PAHs), which are ubiquitous contaminants in the environment, cause great public health concern due to their carcinogenicity, teratogenicity, and genotoxicity (IARC, 2010; Kim et al., 2013). The main exposure routes of PAHs in the general population are through air inhalation, cigarette smoke inhalation, and food ingestion (Ding et al., 2012). Due to rapid urbanization, extensive motorway networks, and the popularity of car transport in China, an increase in the emission and

*

This paper has been recommended for acceptance by Charles Wong. * Corresponding author. E-mail address: [email protected] (Y. Yu).

environmental concentrations of PAHs is predicted (Wang et al., 2016). High concentrations of PAHs in road dust (14e21 mg kg-1) and surface sediments (107e1710 ng g-1 dry) were detected in Shanghai (Liu et al., 2007, 2008). This may lead to high intake in the general population in this region. Gestation is a sensitive period. Environmental contaminants can be transferred via the placenta and exert adverse effects on fetus (Barr et al., 2007; Bocskay et al., 2005; Pedersen et al., 2010). For example, placental benzo(a)pyrene (BaP) may disturb the differentiation of placental trophoblastic cells (Rappolee et al., 2010). A positive correlation between elevated concentrations of PAHs and an increased risk of neural tube defects has been observed (Langlosis et al., 2012; Ren et al., 2011). In addition, adverse pregnancy outcomes have been associated with exposure to PAHs (AlSaleh et al., 2013; Edwards et al., 2010; Pedersen et al., 2013; Yi

http://dx.doi.org/10.1016/j.envpol.2016.12.046 0269-7491/© 2016 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Zhang, X., et al., Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China, Environmental Pollution (2016), http://dx.doi.org/10.1016/j.envpol.2016.12.046

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X. Zhang et al. / Environmental Pollution xxx (2016) 1e9

et al., 2015). Furthermore, placental exposure to PAHs can result in long-term adverse effects in children, including developmental delays and behavioral problems (Perera et al., 2009, 2012). It is well known that fetuses and infants are more susceptible to the adverse effects of PAHs than adults. As a result, prenatal exposure to PAHs is causing a lot of public health concern. The measurements of contaminants in umbilical cord serums and placentas are a useful means of assessing prenatal exposure and potential toxic effects on fetuses (Sakamoto et al., 2016; Yu et al., 2013). Many organic pollutants, such as organochlorine pesticides, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), perfluorooctanoate, perfluorooctanesulfonate, synthetic musks, and nanoparticles have been detected in umbilical cord serums and placentas, and their transplacental transfer has been investigated (Mori et al., 2014; Mose et al., 2007; Poulsen et al., 2015; Yu et al., 2013). Some researchers have reported the transplacental transfer of PAHs (Karttunen et al., 2010; Sexton et al., 2011; Tsang et al., 2011). However, it is difficult to compare the data, because different units and detection methods were used. For example, Tsang et al. (2011) found that the total PAH concentrations were lower in umbilical cord serums (1160 ng g-1 lipid) than those in maternal bloods (1460 ng g-1 lipid). However, Sexton et al. (2011) proposed that the PAH concentrations in umbilical cord serums generally exceeded those in paired maternal bloods, and the data were given at the ng mL
1. The concentrations of hydroxylated PAHs in urine and PAHDNA adducts in cord serums and cord tissues were also reported (Perera et al., 2012; Thai et al., 2015; Yi et al., 2015). In addition, maternal age, dietary intake, lifestyle, and residence region can have a variable influence on particular contaminants and matrices (Jakobsson et al., 2012; Lee et al., 2013; Luo et al., 2016; Pedersen et al., 2013). The extent of transplacental transfer from the mother to the fetus depends on the physical characteristics of the maternal-placental-embryonic-fetal group, and the physiochemical and structural characteristics of the contaminants (Mori et al., 2014; Needham et al., 2011; Vizcaino et al., 2014). Thus, a systematic study is needed to determine the placental transfer of PAHs. Therefore, to comprehensively study the partition of PAHs from the mother to the fetus, 95 paired samples of maternal serum, umbilical cord serum, and placenta (in total 285 individual samples) from a mother-infant cohort in Shanghai were collected and analyzed. The main objectives of the present study were: (1) to investigate the occurrence of PAHs in maternal and umbilical cord serums, and placentas; (2) to evaluate the transplacental transfer of PAHs from mother to fetus, and investigate the possible mechanism involved. 2. Materials and methods 2.1. Sample collection Volunteers were randomly enrolled at a hospital located in Shanghai during 2013 and 2014. Data including age, occupation, education, parity, dietary habit, and neonatal parameters were recorded by using questionnaires. Women with possibly occupational exposure to PAHs were excluded. Although samples and data were collected blindly, selection bias may not completely be excluded. Paired samples (pair number: n ¼ 95) of maternal serum, umbilical cord serum, and placenta were collected at the time of delivery from 95 donors. Serums were obtained from blood samples by centrifugation and preserved in brown glass test tubes at
20  C until analysis. Placenta samples were lyophilized and stored in sealed plastic bags at
20  C. The Ethics Committee of the hospital approved the study protocol. Informed consents were

obtained from all the volunteers. 2.2. Chemicals The target PAH compounds included acenaphthylene (ACY), acenaphthene (ACE), fluorene (FLO), phenanthrene (PHE), anthracene (ANT), fluoranthene (FLA), pyrene (PYR), benz(a)anthracene (BaA), chrysene (CHR), benzo(b)fluoranthene (BbF), benzo(k)fluoranthene (BkF), indeno(l,2,3-cd)pyrene (IcdP), BaP, dibenz(a,h) anthracene (DahA), and benzo(g,h,i)perylene (BghiP). The standards of the 15 PAHs were purchased from AccuStandard Incorporated (Connecticut, USA). Mixed surrogate standards including ACY-d8, PHE-d10, FLA-d10, PYR-d10, BaA-d12, and BghiP-d12 were obtained from Cambridge Isotope Laboratories, Incorporated (Andover, USA). Hexane and dichloromethane were of analytical grade and were re-distilled before use. 2.3. Sample treatment Frozen serum samples (4e5 mL for maternal serum and 8e12 mL for umbilical cord serum) were warmed to room temperature and spiked with 2.5 ng of surrogate standards. The serum samples were treated as previously described with some modifications (Zhang et al., 2015). Briefly, hydrochloric acid and isopropanol were added before liquid-liquid extraction. Then, 30 mL of n-hexane was used for the extraction (3  10 mL). For placenta samples, 3e4 g of lyophilized sample was spiked with 2.5 ng of surrogate standards and then was Soxhlet-extracted with 200 mL of dichloromethane for 72 h. All the extracts were concentrated and their lipid contents were determined by using a gravimetric method. After the lipids were weighed and recorded, they were redissolved in n-hexane, and then cleaned up by passing them through a glass column (300 mm  25 mm i.d.) packed with Biobeads S-X3 (Bio-Rad Laboratories, Hercules, CA, USA). A silica/ alumina column (2:1) was used for further purification. The sequential eluents were n-hexane and n-hexane/dichloromethane (7:3, v/v). Finally, the fractions containing PAHs were collected and concentrated to 50 mL. Hexamethylbenzene was then added as the injection internal standard. 2.4. Instrument analysis PAHs were analyzed using an Agilent 6890N gas chromatograph equipped with a 5975 mass selective detector. A DB-5MS (30 m  0.25 mm  0.25 mm, J & W Scientific, USA) fused-silica capillary column was used. The oven temperature was changed as follow: 80  Ce180  C at a rate of 3  C min-1, 180  Ce240  C (held for 1 min) at 5  C min
1, and 240  Ce290  C (held for 2 min) at 3  C min
1. A splitless injection mode at 280  C was used. The mass spectrometer was operated in electron impact mode with selected ion monitoring. The compounds were quantified by two diagnostic ions and the retention time as described previously (Zhang et al., 2015). 2.5. Quality assurance and quality control A procedural blank was included in each batch of samples, and the values of the procedural blanks were subtracted from the sample concentrations. Surrogate standards were used with average recoveries of 77.3 ± 25.9% for ACY-d8, 113 ± 19.7% for PHEd10, 108 ± 25.0% for FLA-d10, 107 ± 25.9% for PYR-d10, 90.7 ± 22.5% for BaA-d12, and 78.5 ± 26.0% for BghiP-d12. The limits of detection (LODs) were derived from six blanks spiked with 1 ng of standards, and defined as the products of 3.36 and the standard deviations of the results. The LODs were between 2 and 32 ng g-1 lipid. The limits

Please cite this article in press as: Zhang, X., et al., Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China, Environmental Pollution (2016), http://dx.doi.org/10.1016/j.envpol.2016.12.046

X. Zhang et al. / Environmental Pollution xxx (2016) 1e9

of quantification (LOQ) were 3e64 ng g-1 lipid, which were twofold of the LODs. Standard calibration curves were used for the quantification of all targets. The combined concentrations of BbF and BkF were reported due to overlapping of their peaks.

2.6. Calculations and statistical analysis Placental transfer was calculated using the concentration ratios between paired samples as follows:

F=M ¼ CU =CM or P=M ¼ CP =CM

Table 1 Socio-demographic characteristics of the population studied.

Mother (n ¼ 95) Maternal age (years) 25 26e30 31e35 36 Pre-pregnancy body mass index (kg/m2) underweight (<18.5) normal weight (18.5e25) overweight (>25) Weight gained at delivery (kg) Pairty primiparous multiparous Living area urban suburb Education level secondary university Newborn (n ¼ 95) Gender male female Birth body weight (g) Birth body length (cm) Birth circumference (cm) n: Number of samples. a Arithmetic mean (standard deviation).

3. Results and discussion 3.1. Socio-demographic characteristics The cohort included 95 participants and their 95 neonates. Socio-demographic characteristics including maternal age, weight before and at delivery, educational level, dietary habit, and residence region were obtained by using a questionnaire and are summarized in Table 1. The average maternal age was 29.3 ± 3.7 years. The mean body mass index was 22.0 ± 2.8. The number of male neonates was close to female neonates (49 versus 46). The mean birth weight of the neonates was 3353 ± 345 g. Of the 95 participants, 86 were primiparous women. 3.2. Concentrations and distribution patterns in the three matrices

where CU, CM, and CP (ng g
1 lipid) are the lipid-based concentrations of a PAH compound in umbilical cord serums, maternal serums, and placentas, respectively. Concentration ratios were evaluated for values below the LOQ and outliers (concentration values exceeded 1.5-folds of the interquartile ranges of the interquartiles) in all matrices were excluded. Concentrations were generally reported based on lipid-adjusted values, unless otherwise specified. The concentrations below the LOQs but above the LODs were assumed to be halves of the LOQs, whereas the concentrations below the LODs were zero. The Kolmogorov-Smirnov test showed that PAH concentrations and the influencing factors had abnormal distributions (p > 0.05). The relationships between PAH concentrations, and between concentrations and other factors were analyzed using nonparametric correlation (Spearman). The Mann-Whitney U test and Wilcoxon Signed-Rank test were used to analyze the differences between the two geographical areas and between data in the two matrices, respectively. All statistical analyses were conducted with SPSS software, and statistical significance was set at a p-value lower than 0.05.

Variables

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n (%) 29.3 (3.7)a 10 (10.5) 51 (53.7) 26 (27.4) 8 (8.4) 22.0 (2.8)a 10 (10.5) 72 (75.8) 13 (13.7) 15.3 (4.0)a 86 (90.5) 9 (9.5) 77 (81.1) 18 (18.9) 49 (51.6) 46 (48.4)

49 (51.6) 46 (48.4) 3353 (345)a 50.0 (0.5)a 42.2 (31.4)a

The concentrations of 15 individual PAH compounds detected in maternal serums, umbilical cord serums, and placentas are shown P in Fig. 1. The average concentrations of total PAHs ( PAH15) in maternal and umbilical cord serums were 1290 and 1150 ng g-1 lipid, respectively, which were significantly higher (Wilcoxon Signed-Rank, p < 0.001) than those in placentas (673 ng g-1 lipid). The average BaP equivalent concentrations (BaPeq) in maternal (22.4 ng g-1 lipid) and umbilical cord serums (20.4 ng g-1 lipid) were also higher (Wilcoxon Signed-Rank test, p < 0.001) than that in placentas (3.2 ng g-1 lipid). Both the lipid-based concentrations of P PAH15 and BaPeq in maternal serums were not significantly different to those in umbilical cord serums (Wilcoxon Signed-Rank test, p ¼ 0.215e0.299). The median concentrations on the basis of volume in the three matrices decreased in the order of maternal serum (8.87 ng mL-1), placenta (4.89 ng g-1 wet weight), and cord serum (2.83 ng mL-1). In the present study, the median concentrations of PAHs with three and four rings, including ACY, ACE, FLO, ANT, FLA, PYR, PHE, BaA, and CHR, in maternal serums (1030 ng g-1 lipid) were similar to those in Hong Kong (964 ng g-1 lipid) (Qin et al., 2011). However, based on the serum volume (i.e. wet weight), the concentrations (0.70e3.15 ng mL-1) were almost one order of magnitude higher than those in the USA (0.1e0.5 ng mL-1) determined during 2005e2006, when the main pollutants of FLO, FLA, PYR, and PHE P were included (Sexton et al., 2011). The PAH15 in umbilical cord serums were similar to those in Beijing (1370 ng g-1 lipid) and Hong Kong (1160 ng g-1 lipid) determined during 2005e2006 (Tsang et al., 2011; Yu et al., 2011). As for the concentrations in placentas, our data were also comparable to those in Beijing (819 ng g-1 lipid) and India (1050 ng g-1 lipid) (Singh et al., 2008; Yu et al., 2011). As a whole, the present data were similar to those reported in Beijing and Hong Kong, suggesting that the Shanghai cohort also had a high internal burden of PAHs (Yu et al., 2011). PHE, FLO, PYR, and FLA were the predominant PAHs in the three matrices. Among the four compounds, the median concentrations of PHE were the highest with the concentrations in maternal serums, umbilical cord serums, and placentas being 403, 382, and 416 ng g-1 lipid, respectively. The compound with the second highest concentration was FLO and the median concentrations in the three matrices were 207, 172, and 97.7 ng g-1 lipid, respectively. The median concentrations of PYR in maternal and umbilical cord serums (93.5 and 109 ng g-1 lipid, respectively) were higher than those of FLA (83.2 and 71.6 ng g-1 lipid, respectively). However, this sequence was reversed in placentas, i.e., 30.2 and 43.2 ng g-1 lipid for PYR and FLA, respectively. All of the dominant PAHs were low molecular weight compounds as observed in previous reports (Qin et al., 2011; Yu et al., 2011), although the order of decreased concentrations was different. In the present study, the sequence of individual PAHs was as follows: PHE > FLO > PYR > FLA in serum

Please cite this article in press as: Zhang, X., et al., Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China, Environmental Pollution (2016), http://dx.doi.org/10.1016/j.envpol.2016.12.046

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Please cite this article in press as: Zhang, X., et al., Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China, Environmental Pollution (2016), http://dx.doi.org/10.1016/j.envpol.2016.12.046

Fig. 1. The concentration distribution of PAHs in the three matrices (A: the lipid-based concentrations in maternal serum; B: the lipid-based concentrations in umbilical cord serum; C: the lipid-based concentrations in placenta; D: the volume-based concentrations in maternal serum; E: the volume-based concentrations in umbilical cord serum; and F: the wet weight concentrations in placenta. Horizontal lines of the box from the bottom to top indicate 25%, 50%, and 75% values, the squares represent mean values. The whiskers extend to the last observation within 1.5-fold of the interquartile range. The crosses outside the whiskers represent the lowest and highest value. ACY: acenaphthylene; ACE: acenaphthene; FLO: fluorene; PHE: phenanthrene; ANT: anthracene; FLA: fluoranthene; PYR: pyrene; BaA: benz(a)anthracene; CHR: chrysene; BbkF: combined of benzo(b)fluoranthene and benzo(k)fluoranthene; BaP: benzo(a)pyrene; DahA: dibenz(a,h)anthracene; IcdP: indeno(l,2,3-cd)pyrene; BghiP: benzo(g,h,i)perylene.).

X. Zhang et al. / Environmental Pollution xxx (2016) 1e9

samples, and PHE > FLO > FLA > PYR in umbilical cord serums in Beijing and FLO > PYR > PHE > FLA in maternal serums in Hong Kong (Tsang et al., 2011; Yu et al., 2011). Of the carcinogenic PAHs, the main compounds were CHR, BaA, and B(bþk)F, with median concentrations of 40.6, 19.9, and 25.2 ng g-1 lipid in maternal serums, 35.0, 19.5, and 30.0 ng g-1 lipid in umbilical cord serums, and 4.5, 5.3, and 6.4 ng g-1 lipid in placentas, respectively. The dominant carcinogenic PAHs were consistent with previous reports from Hong Kong and Beijing (Tsang et al., 2011; Yu et al., 2011). However, our results were different from those observed in Guiyu, a notorious e-waste dismantling site in Guangdong province, China (Guo et al., 2012), where the major carcinogenic PAHs in umbilical cord serums were B(bþk)F, IcdP, and DahA. This may be attributed to point source pollution. According to the number of rings in their structures, the percentages of PAHs with three rings in maternal serums, umbilical cord serums, and placentas were higher (67.2e83.7%) than those with other numbers of rings (Fig. 2). The average concentrations of PAHs with four rings in the matrices accounted for approximately 15.1e27.6% of the totals. However, in terms of BaPeq, the percentages of PAHs with five rings (higher equivalency factor) were higher (41.6e69.4%) than others. The average contributions of PAHs with three rings in BaPeq were 10.2%, 9.9%, and 27.8% in maternal serums,

Fig. 2. The distribution patterns of PAHs in the three matrices (A: the lipid-based concentration percentage plot, data were normalized to the total lipid-based concentrations of PAHs. B: the lipid-based BaPeq concentration percentage plot, data were normalized to the total lipid-based BaPeq concentrations. Error bars represent standard deviations, n ¼ 95).

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umbilical cord serums, and placenta samples, respectively. The distribution pattern, based on lipid-adjusted concentrations, in maternal serums was in accordance with that in umbilical cord serums. This may indicate a strong correlation between PAHs in maternal serums and umbilical cord serums, and their transfer from mother to fetus. 3.3. Factors influencing the concentrations of PAHs To avoid the possible influence of parity, only data from primapara women were considered in the following section. The median concentrations of PAHs in maternal and umbilical cord serums from mothers with consumption of fish or meat fewer than three times a week (n ¼ 5) were 935 and 819 ng g-1 lipid, respectively. The group who consumed fish or meat more than five times a week (n ¼ 53) showed the concentrations of 1120 and 987 ng g-1 lipid in maternal and cord serums, respectively. The difference between these two groups was not statistically significant (MannWhitney U test, p ¼ 0.239e0.353). There was no obvious change (Mann-Whitney U test, p ¼ 0.445) in maternal burden between the mothers living in urban areas (median: 1120 ng g-1 lipid, n ¼ 69) and those in suburban areas (median: 1020 ng g-1 lipid, n ¼ 17). The P dependence of PAH15 on social-demographic characteristics was not observed. In the present study, no obvious correlation was observed between the frequency of meat and fish consumption and PAH concentrations in maternal or umbilical cord serums. This was consistent with previous observations that higher rates of fish consumption did not increase the PAH concentrations in maternal
or umbilical cord serums (Pruneda-Alvarez et al., 2012; Tsang et al., 2011; Yu et al., 2011). Yu et al. (2011) assumed that this may be attributed to the inter-individual variability in the absorption and metabolism of PAHs. PAHs are readily metabolized to epoxy and hydroxyl derivatives and are quickly excreted in urine (Buchet et al., 1992). Their half-lives in blood are a few hours, and only small fractions are stored in human tissues (Barr et al., 2005). Their metabolism and excretion in humans are possibly influenced by several factors. Among these factors, the inter-individual variability is important. For instance, a marked variation in urinary 1hydroxypyrene concentration was observed in a controlled feeding trial in Canada (Viau et al., 2002). Another reason for the lack of association between the human burden of PAHs and the frequency of fish/meat consumption may be attributed to the multiple contributions of food groups on dietary intake, and the contributions of multiple in- and out-door PAH exposure due to inhalation (Singh et al., 2016). Vegetables and cereals were suggested to be the most important contributors to the human burden of PAHs (24.4e37.8%), while fish and meat contributed 8.2e11.8% of the total PAH intake through foods as reported in a study in Beijing (Yu et al., 2011). The cooking process and processing techniques also significantly changed PAH concentrations in foods (Singh et al., 2016). Higher PAH concentrations in foods were found when beef and pork were grilled and roasted (Chung et al., 2011). In addition, inhalation is another important
pathway for exposure to PAHs (Pruneda-Alvarez et al., 2012). Highmolecular-weight PAH exposure through inhalation could account for up to 57% (Yu et al., 2015). The highest contribution to indoor exposure usually originates from tobacco smoke. Relatively higher serum concentrations of PAHs were found in smokers than in nonsmokers (Song et al., 2013). Relatively higher total PAH concentrations were found in the serums of male neonates (median: 1020 ng g-1 lipid, n ¼ 44), compared to those in female neonates (median: 981 ng g-1 lipid, n ¼ 42), but the difference was not statistically significant (MannWhitney U test, p ¼ 0.296). No significant differences (Mann-

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Whitney U test, p ¼ 0.351e0.863) between the concentrations of predominant individual compounds (PHE, FLO, PYR, and FLA) in male and female neonates were observed. These results were not consistent with previous studies where differences in the concentrations of PAHs between male and female neonates were observed (Guo et al., 2012; Qin et al., 2011). Guo et al. (2012) found relatively high carcinogenic PAH concentrations in male neonates in Guiyu, China. They assumed that the metabolism of female neonates may be greater in comparison with male neonates. However, lower PAH concentrations in male neonates compared to female neonates were observed by Qin et al. (2011). In the present study, we assumed that this may be attributed to the effect of maternal exposure, and the inter-individual differences in absorption and metabolism, instead of the gender difference of metabolism. The higher maternal serum concentrations in male neonate group (mothers with male neonates: median 1120 ng g-1 lipid; mothers with female neonates: median 957 ng g-1 lipid; Mann-Whitney U test, p ¼ 0.325) may provide support for this assumption. 3.4. Transplacental transfer of PAHs The presence of PAHs in umbilical cord serums indicated the occurrence of transplacental transfer. The lipid-based concentrations of predominant individual PAHs, including PHE, FLO, PYR, and P FLA, as well as PAH15 in maternal and umbilical cord serums were significantly correlated (Spearman rho ¼ 0.238e0.625, p < 0.05). This significant correlation remained after outliers were removed from the analyses, or after other substitution for values < LOD (such as 1/2 LOD). However, no significant correlation was observed between the lipid-based concentrations in maternal serums and placentas (Spearman rho ¼ 0.153, p > 0.05). The correlations between pollutants in different human tissues are complicated as reported in many previous studies (Lee et al., 2013; Wan et al., 2010; Zhang et al., 2015). Significant maternal-fetal correlations for organochlorine pesticides, PCBs, and PBDEs have been reported, although some results showed low Spearman coefficients (Jakobsson et al., 2012; Needham et al., 2011; Yu et al., 2011). However, no correlation for PBDEs between maternal serums and placentas, or between maternal and umbilical cord serums were found (Antignac et al., 2009; Bergonzi et al., 2011). Yu et al. (2011) suggested correlations between low molecular weight PAHs in paired human milk-placenta, or paired placenta-umbilical cord serum, but the numbers of the samples were limited. The statistically significant correlation on maternal-fetal serum concentrations suggested a predominant maternal source that transfers PAHs to the fetus. In previous study, Vizcaino et al. (2014) also observed significant relationships on some PCB and PBDE congeners between mother and newborn. And maternal source of PCBs and PBDEs was proposed. The lack of correlations between paired maternal serum and placenta in the present study might be attributed to the transformation of PAHs in the placenta. Karttunen et al. (2010) suggested the metabolism of 3H-BaP in placental tissue. Quite a few cytochrome P450 enzymes were expressed in human placenta (Myllynen et al., 2007). To further understand the transplacental transfer of PAHs, the relative percentage distribution of PAHs between maternal and umbilical cord serums (maternal-fetal group), and among maternal serum, placenta, and umbilical cord serum samples (maternalplacental-fetal group) were analyzed (Fig. 3). The relative distributions were calculated on the basis of each paired sample in which the PAH concentrations in all matrices were higher than those of LODs. The lipid-based PAH concentrations in umbilical cord serums ranged from 74% to 125% of those in maternal serums, which was consistent with a previous report from Hong Kong, where the mean concentrations in umbilical cord serums were 57e134% of those in

maternal serums (Tsang et al., 2011). The percentage distributions in maternal-fetal group were higher in mothers (68e77%) than in fetuses (23e32%) when calculated using volume-based concentrations. The distributions in maternal-placental-fetal group were relatively lower in placentas (lipid-based: 9e34%; volume-based: 13e43%) than in maternal serums (lipid-based: 32e49%; volumebased: 42e65%) (Fig. 3). The ratios of concentrations in umbilical cord serum to maternal serum (F/M) and in placenta to maternal serum (P/M) in paired samples were analyzed to characterize the transplacental transfer of individual PAHs. According to the suggestion of Needham et al. (2011), the data of outliers and those lower than LOQ values should be excluded for the ratio calculation, and the reliably measurable concentrations should be more than 10 pairs. As a result, the ratios of ACY, ACE, FLO, PHE, ANT, FLA, PYR, BaA, CHR, and B(bþk)F were obtained. The median F/M ratios varied between 0.79 and 1.36 on lipid basis, and between 0.26 and 0.43 when concentrations were based on volume (wet weight) (Table 2). The P/M ranges were 0.13e1.04 on lipid basis, and 0.15e1.02 based on volume (wet weight). The median F/M ratios were mostly close to one, and the P/M ratios were <1, with the exception of PHE when ratios were calculated using lipid-adjusted concentrations. Haddad et al. (2000) proposed that, for lipophilic contaminants with a logarithm of octanol-water partition coefficient (log KOW) higher than four, the distribution of these chemicals will be determined by their solubility in lipids of tissues and blood. Partition ratios between these tissues and blood would be close to one when the concentrations were based on lipid. The F/M ratio values in the present study (mostly close to 1) indicated that passive diffusion may control the transplacental transfer of PAHs from the maternal serum to the fetal circulation (Myllynen et al., 2005). In addition, other processes may affect the distribution of compounds between maternal serum and placenta (Vizcaino et al., 2014). The placenta is a complex tissue due to its mixed maternal/fetal origin. Many metabolic enzymes and placental transporter proteins are expressed in the placenta (Evseenko et al., 2006). The transporter proteins can facilitate the transfer of xenobiotics, thus possibly influencing the distribution and accumulation of xenobiotics in the €h€ placenta (Myllynen and Va akangas, 2013). The enzymes expressed in the placenta may also contribute to this effect. By using the human placental perfusion method, Karttunen et al. (2010) observed DNA adducts in placental tissue after 6 h perfusion. They suggested that the placenta itself could activate BaP metabolism and form DNA adducts. Another report found that the addition of human serum albumin increased the BaP transfer through the placenta in the placental perfusion model (Mathiesen et al., 2009). The placenta can act as a partial barrier to some environmental contaminants (Needham et al., 2011). 3.5. Compound-specific transfer of PAHs The P/M and F/M ratios varied depending on the individual PAH compounds (Table 2). In the present study, PHE showed the highest accumulation in placenta (P/M: 1.04), followed by FLA (0.53) and FLO (0.43), when the concentrations were based on lipid. This may indicate that the transfer of individual PAH compound from maternal serum to placenta is different. The compound-specific transfer of PBDEs from maternal serum to cord serum was proposed by Jakobsson et al. (2012). Mori et al. (2014) also observed that the transfer rate of each PCB or dioxin congener/isomer from maternal serum to umbilical cord was different. The rates of total PCBs and Hexa-CB for umbilical cord/maternal serum were almost the same (Mori et al., 2014). These studies indicated that contaminant properties may affect the transplacental transfer to a great extent (Lancz et al., 2015).

Please cite this article in press as: Zhang, X., et al., Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China, Environmental Pollution (2016), http://dx.doi.org/10.1016/j.envpol.2016.12.046

X. Zhang et al. / Environmental Pollution xxx (2016) 1e9

7

Fig. 3. The relative distribution percentages of maternal-fetal and maternal-placental- fetal groups (A: the lipid-based concentration percentages of the individual PAH compound in maternal-fetal groups; B: the lipid-based concentration percentages of the individual PAH compound in maternal-placental-fetal groups; C: the volume-based concentration percentages of the individual PAH compound in maternal-fetal groups; D: the volume-based concentration percentages of the individual PAH compound in maternal-placental-fetal groups. Error bars represent standard deviations, n ¼ 63e95. ACY: acenaphthylene; ACE: acenaphthene; FLO: fluorene; PHE: phenanthrene; ANT: anthracene; FLA: fluoranthene; PYR: pyrene; BaA: benz(a)anthracene; CHR: chrysene; BbkF: combined of benzo(b)fluoranthene and benzo(k)fluoranthene).

Table 2 Median concentration ratios in maternal-cord blood pair samples and maternal-placenta pair samples. Molecular weight

Number of rings

Log KOW

F/M ratios

a

Number of pairs

P/M ratios Median (IQR) ng mL

ACY ACE FLO PHE ANT FLA PYR BaA CHR B(bþk)F

152 154 166 178 178 202 202 228 228 252

3 3 3 3 3 4 4 4 4 5

3.94 3.92 4.18 4.46 4.45 5.16 4.88 5.76 5.81 5.78/6.11

89 87 87 87 86 89 82 80 72 52

0.39 0.26 0.29 0.36 0.42 0.34 0.43 0.35 0.35 0.40


1

(0.32) (0.28) (0.25) (0.23) (0.37) (0.19) (0.26) (0.25) (0.22) (0.25)

b

Number of pairs ng g 1.13 0.79 0.88 1.02 1.36 0.99 1.17 1.03 0.97 1.25


1

lipid

(1.04) (0.76) (0.94) (0.68) (1.17) (0.68) (0.77) (0.79) (0.78) (0.80)

72 82 81 88 76 90 81 83 51 55

Median (IQR) ng mL
1

ng g
1 lipid

0.38 0.23 0.41 1.02 0.30 0.48 0.27 0.27 0.15 0.23

0.39 0.26 0.43 1.04 0.31 0.53 0.31 0.31 0.13 0.26

(1.31) (0.30) (0.49) (0.71) (0.79) (0.66) (0.36) (0.20) (0.17) (0.11)

(1.36) (0.30) (0.42) (0.68) (0.68) (0.70) (0.35) (0.21) (0.17) (0.16)

IQR: interquartile range. a The concentration ratio of umbilical cord serum over maternal serum. b The concentration ratio of placenta over maternal serum.

In the present study, the P/M values calculated on lipid basis were negatively correlated to their log KOW (Spearman rho ¼
0.105, p < 0.01, n ¼ 759) (Fig. 4). The F/M values also decreased slightly when their log KOW increased, though their association was not statistically significant at the 95% confidence level

(Spearman rho ¼ 0.055, p > 0.05, n ¼ 811). This was consistent with the results for PCBs as reported by Lancz et al. (2015). They observed an inverse association between log F/M and log KOW of PCBs. Needham et al. (2011) observed that a greater degree of chlorination of PCBs resulted in lower transfer from maternal

Please cite this article in press as: Zhang, X., et al., Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China, Environmental Pollution (2016), http://dx.doi.org/10.1016/j.envpol.2016.12.046

8

X. Zhang et al. / Environmental Pollution xxx (2016) 1e9

Fig. 4. The relationships between lipid-based concentration ratios and log KOW (A: umbilical cord serum to maternal serum; B: placental to maternal serum. Each point represents a mean value ± standard deviation, n ¼ 51e89).

serum to milk. A decreasing trend between maternal and fetal PBDE concentration ratios at higher degrees of bromination was reported in some studies (Jakobsson et al., 2012; Needham et al., 2011). The increased degree of chlorination or bromination of PCBs and PBDEs was paralleled by an increase in lipophilicity. Transplacental transfer rates of PCBs, calculated through maternal serum, umbilical cord serum, and cord tissue, were negatively correlated with molecular weight (Mori et al., 2014). It is well known that for these hydrophobic congeners or homologues, their KOW values and molecular weights are interrelated (Lancz et al., 2015). Our results were in agreement with these studies, and showed that PAH compounds with lower KOW were more likely to transfer from mother to fetus via the placenta. Needham et al. (2011) proposed that transfer of contaminants from the mother to the fetus is more complex than simple diffusion, and the overall effect of the physicochemical properties involved was difficult to predict. If large molecules penetrate the placenta and reach the fetus, they may be difficult to be eliminated due to the low biotransformation capabilities of the fetus (Vizcaino et al., 2014). More studies on the metabolism in maternal-placentalfetal group and the influence on transplacental transfer are needed. 4. Conclusions PAHs were widely detected in maternal serums, umbilical cord serums, and placentas, and three-ringed PAHs dominated. The P PAH15 and BaPeq on lipid-based concentrations decreased in the order of maternal serum > umbilical cord serum > placenta, while the order based on volume (wet weight) was maternal serum > placenta > umbilical cord serum. The significant correlation between maternal serum and umbilical cord serum concentrations suggested transplacental transfer from mother to fetus. The median concentration ratios of F/M were close to one (from 0.79 to 1.36 on lipid basis), while those of P/M were lower than one on lipid basis, with the exception of PHE. The F/M ratio values in the present study indicated that passive diffusion may control the transplacental transfer of PAHs from mother to fetus. Finally, the transfer ratios of individual PAH compounds varied and negatively correlated with their log KOW, which indicated that PAHs with low KOW were more likely to transfer from mother to fetus via the placenta. Notes We declare there is no competing financial interest. Acknowledgements This study was financially supported by the National Nature

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Please cite this article in press as: Zhang, X., et al., Transplacental transfer of polycyclic aromatic hydrocarbons in paired samples of maternal serum, umbilical cord serum, and placenta in Shanghai, China, Environmental Pollution (2016), http://dx.doi.org/10.1016/j.envpol.2016.12.046