Placental concentrations of xenoestrogenic organochlorine pesticides and polychlorinated biphenyls and assessment of their xenoestrogenicity in the PA-MAMI mother-child cohort.

BACKGROUND: Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCB), they have contributed to the exposure of women to persistent organic pollutants (POPs). These compounds can cross the placental barrier and interfere with the hormonal system of newborns. AIM: To determine concentrations of OCPs and PCBs and their xenoestrogenic activity in placentas of women from the PA-MAMI cohort of Panama. METHODS: Thirty-nine placenta samples from women in the Azuero peninsula (Panama) were analyzed. Five OCPs [p-p'-dichlorodiphenyldichloroethylene (p-p'-DDE), beta-hexachlorohexane (ß-HCH), γ-hexachlorohexane (lindane), hexachlorobenzene (HCB) and mirex] and three PCB congeners (PCB-138, PCB-153 and PCB-180) were quantified in placenta extracts. The xenoestrogenic activity of extracts was assessed with the E-Screen bioassay to estimate the total effective xenoestrogen burden (TEXB). RESULTS: All placental samples were positive for at least three POP residues and >70% for at least six. The frequencies of quantified OCPs ranged from 100% for p,p'-DDE and HCB to 30.8% for ß-HCH. The highest median concentration was for lindane (380.0 pg/g placenta), followed by p,p'-DDE (280.0 pg/g placenta), and HCB (90.0 pg/g placenta). Exposure to p,p'-DDE was associated with greater meat consumption, suggesting that animal fat is a major source of exposure to DDT metabolites. The frequency of detected PCBs ranged between 70 and 90%; the highest median concentration was for PCB 138 (17.0 pg/g placenta), followed by PCB 153 (16.0 pg/g placenta). All placentas were positive in the estrogenicity bioassay with a median TEXB-α of 0.91 pM Eeq/g of placenta. Exposure to lindane was positively associated with the xenoestrogenicity of TEXB- α, whereas this association was negative in the case of exposure to PCB 153. CONCLUSIONS: To our best knowledge, this study contributes the first evidence on the presence of POPs and xenoestrogenic burden in placentas from Latin-American women. Given concerns about the consequences of prenatal exposure to these compounds on children's health, preventive measures are highly recommended to eliminate or minimize the risk of OCP exposure during pregnancy.

Assessment of urinary aromatic amines in Brazilian pregnant women and association with DNA damage: Influence of genetic diversity, lifestyle, and environmental and socioeconomic factors.

Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p-aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R2 = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential.

Polychlorinated biphenyls (PCBs) in the colostrum samples from the Yangtze River Region: Exposure profile and risk assessment.

Polychlorinated biphenyls (PCBs) may transfer into the neonates through the placental transfer and via breastfeeding after the delivery, thus might be harmful to the infant. Sixty colostrum samples in the Yangtze River Region were collected to investigate the concentration, distribution pattern, and enantiomer characteristic of the PCB exposure. Among all samples, over 90% of pollutants were tetra-to hepta-chlorinated PCBs. The sum concentration of the PCB was 512 (IQR: 322-856) ng g-1 lipid weight. Enantiomer fraction (EF) of PCB 95 and PCB 149 was found lower than the racemic value, while EFs of PCB 45 and PCB 136 were found higher and near-racemic state, respectively. The concentration pattern and enantiomeric properties of the PCBs indicated that the mothers from Mianyang had a recent exposure to PCBs. Among all samples, similar exposure and metabolic pathways of the PCB congeners were observed. PCB exposure showed no significant correlation with the birth outcome of the infants, but 43.3% of the infants have potential health risks via breastfeeding.

Risk assessment of occupational exposure to anesthesia Isoflurane in the hospital and veterinary settings.

Despite the modern ventilation and waste anesthetic gas (WAG) scavenging systems, occupational exposure to common volatile anesthesia, isoflurane, can occur in the hospital and veterinary settings, but limited information exists on potential exposure and health risk of isoflurane. We assessed exposure dose rates and risks among clinicians and veterinary professionals from occupational exposure to isoflurane. Through a critical review of open literature (1965 to 2020), we summarized potential adverse effects and exposure scenarios of isoflurane among the professional groups, including anesthetists, nurses, operating room personnel, researchers, and/or veterinarians. Deterministic United States National Research Council/Environmental Protection Agency's risk assessment framework (hazard identification, dose-response relationship, exposure assessment and risk characterization) was used to compute inhalation Reference Doses (RfDs), Average Daily Doses (ADDs), and Hazard Quotient (HQ) values-an established measure of non-carcinogenic (systemic) risks-from exposure to isoflurane to workers in hospital and veterinary settings. We identified the central nervous system as the main target for isoflurane, and that isoflurane has dose-dependent effects on cardiac hemodynamics, can impair pulmonary functions and potentially cross the utero-placental barrier leading to congenital malformation in fetus. Based on the modelled RfDs (range 0.8003-7.55 mg/kg-day) and ADDs (range 0.071-1.9617 mg/kg-day), we estimated 56 different HQ values, of which 5 HQs were higher than 1 (range 1.099-2.4512) under high exposure scenarios. Our results suggest a significant non-carcinogenic risk from isoflurane exposures among workers in the occupational settings. The findings underscore the need to significantly minimize isoflurane release to protect workers' health in the hospital and veterinary environments.

Lifetime dietary exposure to bisphenol A in the general population and during pregnancy: Foetal exposure and health risk assessment.

Bisphenol A is a well-known chemical substance triggering reprotoxic and endocrine disruptor effects. Pregnancy is considered as a critical period of exposure to BPA because of the foetal sensitivity to endocrine disruption. Because of its wide use in food packaging, BPA is found in common foods and in infant formulae. We used a lifetime approach to simulate dietary exposure trajectories of a French population and to assess the associated health risk. Moreover, a semi-physiological based toxicokinetic model was used to simulate the maternal-foetal exchanges of BPA during pregnancy. Metabolism was taken into account by considering the glucuronidation of BPA by the foetal-placental unit, as well as the reactivation of BPA-glucuronide into BPA in the foetal compartment. From maternal critical daily exposures defined by ANSES based on effects for different endpoints of BPA in the unborn child (i.e. 0.083, 0.17, 0.29 and 0.33 µg/kg bw/d, respectively based on effects on mammary gland, brain and behaviour, metabolism and obesity and female reproductive system), resulting concentrations of BPA in the foetal compartment were estimated and health risk was assessed for the sub-population of unborn children. This work leads to the conclusion that while a health risk due to dietary exposures of the general population can be excluded, this is not the case for the sub-population of pregnant women, in view of the levels of foetal exposure to BPA.

Assessment of biological matrices for the detection of in utero cannabis exposure.

Cannabis consumption has been increasing worldwide among pregnant women. Due to the negative effects of prenatal cannabis exposure, it is necessary to develop an objective, sensitive, and specific method to determine cannabinoids use during pregnancy. In this study, we compared four different biological samples, maternal hair, meconium, umbilical cord, and placenta, for the detection of in utero cannabis exposure. The biological samples were collected from 627 mother-newborn dyads. All hair and meconium samples were analyzed, and umbilical cord and placenta if hair and/or meconium were positive for cannabinoids. Meconium and hair showed to complement each other, with an agreement between hair and meconium results of 96.7% but only 34.3% if just positive results were considered. Umbilical cord and placenta results showed a better agreement with meconium (91.3% and 92.6%, respectively) than with hair (39.1% and 34.6%, respectively). The predominant metabolites in meconium were 11-nor-carboxy-THC (THCCOOH) and 8,11-dihydroxy-THC (diOHTHC), and in umbilical cord and placenta was THCCOOH-glucuronide. Cannabidiol (CBD) and cannabinol (CBN) were detected in meconium but not in any umbilical cord or placenta. For the first time, prenatal marijuana exposure was analyzed and compared in paired hair, meconium, umbilical cord, and placental samples. Hair and meconium positivity rate was similar, but a more sensitive and specific analytical method for the hair may resolve discrepancies between the matrices. Umbilical cord and placenta may be considered suitable alternative matrices to meconium through the determination of THCCOOH-glucuronide as a biomarker of cannabis exposure.

Assessment of chemical mixtures using biomarkers of combined biological activity: A screening study in human placentas.

Humans are simultaneously exposed to complex mixtures of chemicals with limited knowledge on potential health effects, therefore improved tools for assessing these mixtures are needed. As part of the Human Biomonitoring for Europe (HBM4EU) Project, we aimed to examine the combined biological activity of chemical mixtures extracted from human placentas using one in vivo and four in vitro bioassays, also known as biomarkers of combined effect. Relevant endocrine activities (proliferative and/or reporter gene assays) and four endpoints were tested: the estrogen receptor (ER), androgen receptor (AR), and aryl hydrocarbon receptor (AhR) activities, as well as thyroid hormone (TH) signaling. Correlations among bioassays and their functional shapes were evaluated. Results showed that all placental extracts agonized or antagonized at least three of the abovementioned endpoints. Most placentas induced ER-mediated transactivation and ER-dependent cell proliferation, together with a strong inhibition of TH signaling and the AR transactivity; while the induction of the AhR was found in only one placental extract. The effects in the two estrogenic bioassays were positively and significantly correlated and the AR-antagonism activity showed a positive borderline-significant correlation with both estrogenic bioassay activities. However, the in vivo anti-thyroid activities of placental extracts were not correlated with any of the tested in vitro assays. Findings highlight the importance of comprehensively mapping the biological effects of "real-world" chemical mixtures present in human samples, through a battery of in vitro and in vivo bioassays. This approach should be a complementary tool for epidemiological studies to further elucidate the combined biological fingerprint triggered by chemical mixtures.

The concentration of selected elements in the placenta according to selected sociodemographic factors and their effect on birth mass and birth length of newborns.

BACKGROUND AND AIMS: The placenta is a remarkable organ which provides critical transport functions between the maternal and fetal circulations during pregnancy. The demand for mineral components increases during the gestational period, therefore, an appropriate intake of minerals, such as calcium, phosphorus, potassium, magnesium, iron, zinc, copper, and manganese, determines the correct growth and development of a fetus. The aim of the study was to assess the concentration of selected elements in the placenta, and to assess the impact of their concentrations on the birth weight and birth length of newborns. The second aim of the study was to assess the influence of selected sociodemographic factors on the concentration of elements in the placenta. RESULTS: The study demonstrated that the age of mothers affected the concentration of Ca and Mn in the placenta, and their habit of tobacco smoking during the gestational period was associated with higher concentrations of Ca, P, K, Mg, Fe, Cu, and Cd in the placental tissue. The results also showed that concentrations of K, Fe, Zn, and Mn in the placental tissue affected birth length. Furthermore, the association was demonstrated between a higher Cd concentration in the placenta (≥ 0.0503 µg/g) and the birth anthropometric parameters of neonates. CONCLUSIONS: Smoking during pregnancy and environment pollution are the factors that affects the concentration of elements in the placenta and contributes to their high accumulation in the placenta. Smoking during pregnancy causes an increased concentration of cadmium in the placenta which has negative health effects for the newborn. Women living in a big city or village had a higher concentration of cadmium in their placentas compared to women living in smaller cities. The significant influence of some elements (K, Fe, Zn, Cu and Cd) on the newborn's birth parameters was also demonstrated. The results of our research indicate the importance of the mother's lifestyle in providing the placenta with elements, which affects the growth of the fetus.

Assessment of placental metal levels in a South African cohort.

The placenta plays an important role in mediating the effect of maternal metal exposure on fetal development, acting as both barrier and transporter. Term-placenta metal levels serve as an informative snapshot of maternal/fetal exposure during pregnancy and could be used to predict offspring short- and long-term health outcomes. Here, we measured term-placenta metal levels of 11 metals in 42 placentas from the Soweto First 1000 days cohort (S1000, Soweto-Johannesburg, SA). We compared these placental metal concentrations with previously reported global cohort measurements to determine whether this cohort is at increased risk of exposure. Placental metals were tested for correlations to understand potential interactions between metals. Since these samples are from a birth cohort study, we also performed exploratory analyses to determine whether metal levels were associated with placenta and birth outcomes. Most S1000 placental metal levels were similar to other cohorts; however, cadmium (Cd) levels up to 50-fold lower, and essential elements nickel (Ni) and chromium (Cr) level up to 6- and 16-fold lower, respectively. Cd, Se, and Ni were associated with placenta and birth outcomes. Studies are ongoing to examine underlying mechanisms and how these developmental differences affect long-term health.

Assessment of parabens and ultraviolet filters in human placenta tissue by ultrasound-assisted extraction and ultra-high performance liquid chromatography-tandem mass spectrometry.

Increasing concerns have been raised over recent decades about human exposure to Endocrine Disrupting Chemicals (EDCs), especially about their possible effects on embryo, foetus, newborn, and child. Parabens (PBs) and ultraviolet filters (UV-filters) are prevalent EDCs widely used as additives in cosmetics and personal care products (PCPs). The objective of this study was to determine the presence of four PBs and ten UV-filters in placental tissue samples using a novel analytical method based on ultrasound-assisted extraction (UAE) and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Multivariate optimization strategies were used to accurately optimize extraction and clean-up parameters. Limits of quantification ranged from 0.15 to 0.5µgkg-1, and inter-day variability (evaluated as relative standard deviation) ranged from 3.6% to 14%. The method was validated using matrix-matched standard calibration followed by a recovery assay with spiked samples. Recovery percents ranged from 94.5% to 112%. The method was satisfactorily applied for the determination of the target compounds in human placental tissue samples collected at delivery from 15 randomly selected women. This new analytical procedure can provide information on foetal exposure to compounds, which has been little studied.

Assessment of global DNA methylation in the first trimester fetal tissues exposed to maternal cigarette smoking.

AIMS: Maternal cigarette smoking during pregnancy increases the risk of negative health consequences for the exposed child. Epigenetic mechanisms constitute a likely link between the prenatal exposure to maternal cigarette smoking and the increased risk in later life for diverse pathologies. Maternal smoking induces gene-specific DNA methylation alterations as well as global DNA hypermethylation in the term placentas and hypomethylation in the cord blood. Early pregnancy represents a developmental time where the fetal epigenome is remodeled and accordingly can be expected to be highly prone to exposures with an epigenetic impact. We have assessed the influence of maternal cigarette smoking during the first trimester for fetal global DNA methylation. METHODS AND RESULTS: We analyzed the human fetal intestines and livers as well as the placentas from the first trimester pregnancies. Global DNA methylation levels were quantified with ELISA using a methylcytosine antibody as well as with the bisulfite pyrosequencing of surrogate markers for global methylation status, LINE-1, and AluYb8. We identified gender-specific differences in global DNA methylation levels, but no significant DNA methylation changes in exposure responses to the first trimester maternal cigarette smoking. CONCLUSIONS: Acknowledging that only examining subsets of global DNA methylation markers and fetal sample availability represents possible limitations for the analyses, our presented results indicate that the first trimester maternal cigarette smoking is not manifested in immediate aberrations of fetal global DNA methylation.

Assessment of angiogenesis modulators in pregnant women with pre-eclampsia: a case-control study.

PURPOSE: This study aimed to evaluate the serum concentration of factors associated with placental angiogenesis in pre-eclamptic and normotensive pregnant women. METHODS: This was a prospective, cross-sectional, case-control study in which the pro-angiogenic factors PlGF, VEGF and IL-10, and the anti-angiogenic factors IL-6, IL-17 and TNF-α of 55 pregnant women (31 with pre-eclampsia-PE and 24 normotensive), with gestational age ≥20 weeks, were measured in maternal blood through the enzyme-linked immunosorbent assay (ELISA). The Mann-Whitney and Kruskal-Wallis tests were used for comparison between groups. RESULTS: Serum PIGF was reduced in the group of pregnant women with PE when compared with the normotensive women (493.2 ± 55.1 pg/mL vs. 4.4 ± 26.5 pg/mL; p < 0.001). There was no significant difference in PlGF levels in the pre-eclamptic pregnant women in relation to gestational age or proteinuria levels (p > 0.05). The serum levels of VEGF, IL-17, IL-10 and TNF-α were lower in the pregnant women with PE when compared with their normotensive peers, while the IL-6 levels were higher; however, this difference was not statistically significant (p > 0.05). CONCLUSION: Serum PlGF levels were reduced in the pregnant women with PE and were unrelated to disease severity. Serum levels of VEGF, IL-17, IL-10 and TNF-α were reduced in the pre-eclamptic pregnant women when compared with their normotensive peers, without statistically significant differences.

(1)H MRS: a potential biomarker of in utero placental function.

The placenta is a temporary organ that is essential for a healthy pregnancy. It performs several important functions, including the transport of nutrients, the removal of waste products and the metabolism of certain substances. Placental disorders have been found to account for over 50% of stillbirths. Despite this, there are currently no methods available to directly and non-invasively assess placental function in utero. The primary aim of this pilot study was to investigate the use of (1)H MRS for this purpose. (1)H MRS offers the possibility to detect several placental metabolites, including choline, lipids and the amino acids glutamine and glutamate (Glx), which are vital to fetal development and placental function. Here, in utero placental spectra were acquired from nine small for gestational age (SGA) pregnancies, a cohort who are at increased risk of perinatal morbidity and mortality, and from nine healthy gestation-matched pregnancies. All subjects were between 26 and 39 weeks of gestation. Placenta Glx, choline and lipids at 1.3 and 0.9 ppm were quantified as amplitude ratios to that of intrinsic H2O. Wilcoxon signed rank tests indicated a significant difference in Glx/H2O (p = 0.024) between the two groups, but not in choline/H2O (p = 0.722) or in either lipid/H2O ratio (1.3 ppm, p = 0.813; 0.9 ppm, p = 0.058). This study has demonstrated that (1)H MRS has potential for the detection of placental metabolites in utero. This warrants further investigation as a tool for the monitoring of placental function.

Placental alpha-microglobulin-1 and combined traditional diagnostic test: a cost-benefit analysis.

OBJECTIVE: We sought to evaluate if the placental alpha-microglobulin (PAMG)-1 test vs the combined traditional diagnostic test (CTDT) of pooling, nitrazine, and ferning would be a cost-beneficial screening strategy in the setting of potential preterm premature rupture of membranes. STUDY DESIGN: A decision analysis model was used to estimate the economic impact of PAMG-1 test vs the CTDT on preterm delivery costs from a societal perspective. Our primary outcome was the annual net cost-benefit per person tested. Baseline probabilities and costs assumptions were derived from published literature. We conducted sensitivity analyses using both deterministic and probabilistic models. Cost estimates reflect 2013 US dollars. RESULTS: Annual net benefit from PAMG-1 was $20,014 per person tested, while CTDT had a net benefit of $15,757 per person tested. If the probability of rupture is <38%, PAMG-1 will be cost-beneficial with an annual net benefit of $16,000-37,000 per person tested, while CTDT will have an annual net benefit of $16,000-19,500 per person tested. If the probability of rupture is >38%, CTDT is more cost-beneficial. Monte Carlo simulations of 1 million trials selected PAMG-1 as the optimal strategy with a frequency of 89%, while CTDT was only selected as the optimal strategy with a frequency of 11%. Sensitivity analyses were robust. CONCLUSION: Our cost-benefit analysis provides the economic evidence for the adoption of PAMG-1 in diagnosing preterm premature rupture of membranes in uncertain presentations and when CTDT is equivocal at 34 to <37 weeks' gestation.

DDTs in mothers' milk, placenta and hair, and health risk assessment for infants at two coastal and inland cities in China.

This study is a one of the very few investigating the dichloro-diphenyl-trichloroethanes (DDTs) (summation of o,p'-DDE, p,p'-DDE, o,p'-DDD, p,p'-DDD, o,p'-DDT, and p,p'-DDT) in multiple human matrices in mothers' milk, placenta and hair collected from residents from two coastal cities: Guiyu (GY) and Taizhou (TZ) and one inland city: Lin'an (LA). TZ (milk: 360±319ng/g lipid wt.) showed significantly higher concentrations of DDTs than those from LA (milk: 190±131ng/g lipid wt.), whereas, concentrations of DDTs in GY (milk: 305±109ng/g lipid wt.) were in between TZ and LA. In addition, levels of DDTs in the human tissues from TZ (placenta: 122±109ng/g lipid wt.; hair: 79.9±215ng/g dry wt.) were significantly higher than those from Lin'an (placenta: 49.2±30.2ng/g lipid wt.; hair: 10.8±7.09ng/g dry wt.). The above concentrations of DDTs in milk exceeded the Codex Maximum Residue Limits/Extraneous Maximum Residue Limits for milk (20ng/g lipid wt. whole milk), indicating that the human milk samples were grossly polluted. The present study revealed that human specimens collected from the coastal city (TZ) were more contaminated with inland one (LA), based on the levels of DDTs contained in samples which may be due to the higher dietary exposure to DDTs via consumption of contaminated seafood. The estimated daily intakes of DDTs by GY, TZ and LA infants were 1.69±1.86, 1.48±0.79, and 0.95±0.73µg/kg body wt./day, respectively which did not exceed 10µg/kg body wt./day, the provisional tolerable daily intake proposed by the Food and Agriculture Organization/World Health Organization.

The placenta in toxicology. Part III: Pathologic assessment of the placenta.

This short review is derived from the peer-reviewed literature and the experience and case materials of the authors. Brief illustrated summaries are presented on the gross and histologic normal anatomy of rodent and macaque placentas, including typical organ weights, with comments on differences from the human placenta. Common incidental findings, background lesions, and induced toxic lesions are addressed, and a recommended strategy for pathologic evaluation of placentas is provided.

Simultaneous determination of the UV-filters benzyl salicylate, phenyl salicylate, octyl salicylate, homosalate, 3-(4-methylbenzylidene) camphor and 3-benzylidene camphor in human placental tissue by LC-MS/MS. Assessment of their in vitro endocrine activity.

UV-filters are widely used in many personal care products and cosmetics. Recent studies indicate that some organic UV-filters can accumulate in biota and act as endocrine disruptors, but there are few studies on the occurrence and fate of these compounds in humans. In the present work, a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to assess the presence of six UV-filters in current use (benzyl salicylate, phenyl salicylate, octyl salicylate, homosalate, 3-(4-methylbenzylidene) camphor, and 3-benzylidene camphor) in human placental tissue is proposed. The method involves the extraction of the analytes from the samples using ethyl acetate, followed by a clean-up step using centrifugation prior to their quantification by LC-MS/MS using an atmospheric pressure chemical ionization (APCI) interface. Bisphenol A-d16 was used as surrogate for the determination of benzyl salicylate, phenyl salicylate, octyl salicylate and homosalate in negative mode and benzophenone-d10, was used as surrogate for the determination of 3-(4-methylbenzylidene) camphor and 3-benzylidene camphor in positive mode. The found limits of detection ranged from 0.4 to 0.6ngg(-1) and the limits of quantification ranged from 1.3 to 2.0ngg(-1), while variability was under 13.7%. Recovery rates for spiked samples ranged from 97% to 104%. Moreover, the interactions of these compounds with the human estrogen receptor alpha (hERα) and androgen receptor (hAR), using two in vitro bioassays based on reporter gene expression and cell proliferation assessment, were also investigated. All tested compounds, except benzyl salicylate and octyl salicylate, showed estrogenic activity in the E-Screen bioassay whereas only homosalate and 3-(4-methylbenzylidene) camphor were potent hAR antagonists. Although free salicylate derivatives and free camphor derivatives were not detected in the human placenta samples analyzed, the observed estrogenic and anti-androgenic activities of some of these compounds support the analysis of their occurrence and their role as endocrine disrupters in humans.

Maternal hair testing for the assessment of fetal exposure to drug of abuse during early pregnancy: Comparison with testing in placental and fetal remains.

UNLABELLED: Drug use by pregnant women in the first trimester of pregnancy and subsequent fetal exposure during early gestation can be assessed only by repetitive/systematic maternal blood/urine analysis or segmental hair analysis. No evidence of any relationship between maternal/fetal exposure during this specific period of gestation has been demonstrated to date in a human model. METHODS: To clarify drugs toxicokinetics and transplacental passage during early pregnancy, the presence of the most widely used recreational drugs of abuse and metabolites was investigated in the proximal 4cm hair segments of women undergoing voluntary termination of pregnancy (n=280) during the 12th week of gestation and the results were compared to those from placenta and fetal tissue samples in order to verify whether maternal hair testing can reflect fetal exposure and, if so, to what extent. Hair, placenta and fetal remains were analyzed by validated gas chromatography mass spectrometry assays. RESULTS: Eighty one positive hair samples were identified: 60 were positive for cannabis (74.1%), 28 for cocaine (34.6%), 7 for opiates (8.6%), 3 for MDMA (3.7%) and 18.5% were positive for more than one drug. The positive hair test results were confirmed in placenta/fetal tissues in 10 cases out of 60 for cannabis (16. 7%); in 7 out of 28 for cocaine (25%); and none for the 6 opiates positive cases and 3 MDMA cases, respectively. CONCLUSION: Drugs/metabolites in hair of pregnant women can be used as biomarkers of past drug use (repetitive or sporadic), although the use is not always reflected in fetal/placental tissues. There are several possible hypotheses to explain the results: (1) the use occurred before the start of pregnancy, (2) past sporadic consumption which could be measured in hair but not in fetal and placental remains because of the narrow window of drug detection in placental/fetal tissues; (3) the sensitivity of the analytical methods was not high enough for the detection of the minute amount of drugs of abuse and metabolites which reached these tissues (4) there is a large variability in the transplacental passage of drugs of abuse and in the placenta's metabolizing capacity.

Optimization of the matrix solid phase dispersion extraction procedure for the analysis of polybrominated diphenyl ethers in human placenta.

Characterization of prenatal exposure to hazardous chemicals most often relies upon the analysis of cord blood. However, human placenta is an appropriate tissue alternative with noteworthy advantages. Owing to analytical challenges, reports on placental levels of toxic chemicals are limited. The purpose of this study was to establish a reliable, cost-effective, and relatively fast and simple method to extract polybrominated diphenyl ethers (PBDEs) from human placenta for analysis using gas chromatography coupled with mass spectrometry (GC/MS). The matrix solid phase dispersion (MSPD) method was optimized for the extraction and analysis of 43 PBDEs (including BDE209) from human placenta samples. Different sorbents, sample conditions, grinding methods, elution solvents, and single and repeated extractions were compared for their effects on the extraction efficiency. The performance of the optimized method was validated by analyzing spiked placenta samples and a standard reference material of fish tissue. Congener specific PBDE recovery ranged from 91% to 114% for the spiked samples and 89% to 115% for a standard reference material (SRM) of fish tissue. The optimized MSPD procedure was compared with two conventional extraction methods. The extraction efficiency of MSPD was found to be comparable with that of the traditional Soxhlet method and superior to that using a liquid extraction method. Twenty two PBDEs were detected in all of the five samples collected in Chicago in 2008. This is the first description of PBDEs detected in human placentas in the U.S.

Assessment of trace element concentration distribution in human placenta by wavelength dispersive X-ray fluorescence: effect of neonate weight and maternal age.

Trace element status in human placenta is dependent on maternal-neonatal characteristics. This work was undertaken to investigate the correlation between essential trace element concentrations in the placenta and maternal-neonatal characteristics. Placenta samples were collected from total 61 healthy mothers at gestation between 37 and 41 weeks. These samples were investigated with the restriction that the mother's age was 20-40 years old and the neonate's weight was 1-4kg. Percent concentrations of trace elements were determined using wavelength dispersive X-ray fluorescence (WDXRF). The placenta samples were prepared and analyzed without exposure to any chemical treatment. Concentrations of Fe, Cu and Zn in placenta tissues were found statistically to vary corresponding to the age of the mother and weight of the neonate. In the subjects, the concentration of Fe and Cu were increased in heavier neonates (p<0.05) and the concentration of Zn was increased with increasing mother age (p<0.05). Consequently, the Fe, Cu and Zn elements appear to have interactive connections in human placenta.