Perfluorinated alkyl acids in the serum and follicular fluid of UK women with and without polycystic ovarian syndrome undergoing fertility treatment and associations with hormonal and metabolic parameters.

Women with polycystic ovarian syndrome (PCOS) undergoing treatment for infertility could be a sensitive subpopulation for endocrine effects of exposure to perfluorinated alkyl acids (PFAAs), persistent organic pollutants with potential endocrine activity. Women with, PCOS (n = 30) and age- and BMI-matched controls (n = 29) were recruited from a UK fertility clinic in 2015. Paired serum and follicular fluid samples were collected and analysed for 13 PFAAs. Sex steroid and thyroid hormones, and metabolic markers were measured and assessed for associations with serum PFAAs. Four PFAAs were detected in all serum and follicular fluid samples and concentrations in the two matrices were highly correlated (R2 > 0.95): perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). Serum PFOS was positively associated with age (1 ng/mL per yr, p < 0.05) and was higher in PCOS cases than controls (geometric mean [GM] 3.9 vs. 3.1 ng/mL, p < 0.05) and in women with irregular vs. regular menstrual cycles (GM 3.9 vs. 3.0 ng/mL, p = 0.01). After adjustment for confounders, serum testosterone was significantly associated with PFOA, PFHxS, PFNA, and the molar sum of the four frequently detected serum PFAAs (approximately 50 percent increase per ln-unit) among controls but not PCOS cases. HbA1c in PCOS cases was inversely associated with serum PFOA, PFHxs, and sum of PFAAs (2-3 mmol/mol per ln-unit). In controls, fasting glucose was positively associated with serum PFOA and sum of PFAAs (0.25 nmol/L per ln-unit increase in PFAAs). Few other associations were observed. The analyses and findings here should be considered exploratory in light of the relatively small sample sizes and large number of statistical comparisons conducted. However, the data do not suggest increased sensitivity to potential endocrine effects of PFAAs in PCOS patients.

Heffernan AL ，Cunningham TK ，Drage DS ，Aylward LL ，Thompson K ，Vijayasarathy S ，Mueller JF ，Atkin SL ，Sathyapalan T ... -  《-》

Perfluoroalkyl acids in pregnant women from Nunavik (Quebec, Canada): Trends in exposure and associations with country foods consumption.

Perfluoroalkyl acids (PFAAs) are persistent and ubiquitous environmental contaminants that potentially disrupt endocrine system functions. While some PFAAs (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA)) are regulated, currently used fluorotelomer alcohols (FTOHs) can be transported to the Arctic and are degraded in a number of PFAAs which biomagnify in Arctic wildlife (e.g. perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA)). From 2004 to 2017, 279 pregnant Inuit women were recruited as part of biomonitoring projects in Nunavik. Our goal was to evaluate: (i) time-trends in plasma/serum PFAAs levels in pregnant Nunavimmiut women between 2004 and 2017; (ii) compare plasma/serum PFAAs levels in Nunavimmiut women in 2016-2017 to those measured in women of childbearing age in the Canadian Health Measure Survey (CHMS); and (iii) evaluate the associations of PFAAs levels with the consumption of country foods and pregnancy and maternal characteristics during pregnancy in the 97 participants recruited in 2016-2017. Individual blood sample were collected for serum or plasma PFAAs (PFOS, PFOA, pentafluorobenzoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorobutanesulfonic acid (PFBS), perfluorohexane-1-sulfonic acid (PFHxS), PFNA, PFDA, PFUdA) analyses. Socio-demographic data, pregnancy and maternal characteristics and country foods consumption were documented using a questionnaire. Omega-3 and -6 polyunsaturated fatty acids (PUFA) were measured in red blood cell membranes and their ratio used as a biomarker of marine country foods consumption. Time-trends in PFAAs levels were evaluated using ANCOVA models adjusted for relevant co-variables. Serum/plasma levels of PFAAs in the 97 pregnant women aged 16 to 40 years old and recruited in 2016-2017 were compared to those measured in women aged 18 to 40 years old from the CHMS cycle 5 (2016-2017) using the geometric means (GM) and 95% confidence intervals (95% CI). Multivariate regression analyses were performed to examine associations between concentrations of PFAAs and country foods consumption data. Statistically-significant downward time trends were noted for concentrations of PFOS, PFOA and PFHxS in pregnant Nunavik women between 2004 and 2017. Conversely, between 2011 and 2016-2017, PFNA, PFDA and PFUdA maternal serum levels increased by 19, 13 and 21% respectively. Among participants in 2016-2017, mean concentrations for PFNA (GM: 2.4 μg/L), PFDA (0.53 μg/L) and PFUdA (0.61 μg/L) were higher than those measured in women aged 18-40 years old in the Cycle 5 (2016-2017) of the CHMS. PFOA (0.53 μg/L) and PFHxS (0.26 μg/L) were lower than in CHMS, whereas PFBA, PFHxA and PFBS were not detected in 2016-2017. Ratios of serum/plasma levels of PFNA/PFOA, PFNA/PFOS, PFNA/PFHxS and PFUdA/PFDA were significantly higher in the 97 pregnant women from Nunavik recruited in 2016-2017 compared to CHMS, highlighting their distinct exposure profile. In multivariate models, PFHxS, PFOS, PFNA, PFDA and PFUdA levels in 2016-2017 were strongly associated with the omega-3/omega-6 PUFA ratio, indicating a positive association between marine country foods consumption and higher exposure to PFAAs. The exposure of pregnant women to long-chain PFAAs (PFNA, PFDA and PFUdA) increased from 2004 to 2017 in Nunavik. Associations noted between PFAAs levels and the omega-3/omega-6 ratio highlights the importance of implementing additional strict regulations on PFAAs and their precursors to protect the high nutritional quality and cultural importance of country foods in Nunavik.

Caron-Beaudoin É ，Ayotte P ，Blanchette C ，Muckle G ，Avard E ，Ricard S ，Lemire M ... -  《-》

Association of Vitamin D with Perfluorinated Alkyl Acids in Women with and without Non-Obese Polycystic Ovary Syndrome.

Butler AE ，Sathyapalan T ，Das P ，Brennan E ，Atkin SL ... -  《-》

Exposure to Perflouroalkyl acids and foetal and maternal thyroid status: a review.

Boesen SAH ，Long M ，Wielsøe M ，Mustieles V ，Fernandez MF ，Bonefeld-Jørgensen EC ... -  《Environmental Health》

Per- and poly-fluoroalkyl substances (PFASs) in follicular fluid from women experiencing infertility in Australia.

Per- and poly-fluoroalkyl substances (PFASs) have been widely used and detected in human matrices. Evidence that PFAS exposure may be associated with adverse human reproductive health effects exists, however, data is limited. The use of a human matrix such as follicular fluid to determine chemical exposure, along with reproductive data will be used to investigate if there is a relationship between PFAS exposure and human fertility. This study aims to: (1) assess if associations exist between PFAS concentrations and/or age and fertilisation rate (as determined in follicular fluid of women in Australia who received assisted reproductive treatment (ART)); and (2) assess if associations exist between PFAS concentrations and infertility aetiology. Follicular fluids were originally collected from participants who underwent fully stimulated ART treatment cycles at an in vitro fertilisation (IVF) clinic in the period 2006-2009 and 2010-11 in Queensland, Australia. The samples were available for analysis of 32 PFASs including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) using high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). 97 samples were matched with limited demographic data (age and fertilisation rate) and five infertility factors (three known female factors): 1) endometriosis, 2) polycystic ovarian syndrome (PCOS), and 3) genital tract infections - tubal/pelvic inflammation disease; as well as 4) male factor, and 5) idiopathic or unknown from either males or females. SPSS was used for linear regression analysis. PFASs were detected in all follicular fluid samples with the mean concentrations of PFOS and PFOA, 4.9, and 2.4 ng/ml, respectively. A lower fertilisation rate was observed at higher age when age was added as a covariate, but there was no relationship between PFAS concentrations and fertilisation rate. There were few statistically significant associations between PFAS concentrations in follicular fluid and infertility factors. Log-transformed PFHxS concentrations were lower in females with endometriosis (factor 1) than in women who had reported 'male factors' as a reason of infertility, while PFHpA was higher in women who had infertile due to female factors (factor 1-3) compared to those who had infertile due to male factor. PFASs were detected in follicular fluid of Australian women who had been treated at an IVF clinic. PFAS exposure found in follicular fluids is linked to increased risk of some infertility factors, and increased age was associated with decreased fertilisation rate in our data. But there was no relationship between PFAS and ferlitisation rate. Further large-scale investigations of PFAS and health effects including infertility are warranted.

Kim YR ，White N ，Bräunig J ，Vijayasarathy S ，Mueller JF ，Knox CL ，Harden FA ，Pacella R ，Toms LL ... -  《-》