Association of polychlorinated biphenyls with vitamin D in female subjects.

INTRODUCTION: Polychlorinated biphenyls (PCBs) are known endocrine disrupters. A potentially causal association of PCBs with vitamin D has been reported. Higher body mass index (BMI) is associated with lower PCB levels whilst the strongest association of PCBs with BMI is in non-obese individuals. Therefore, this study examined the association of PCBs with vitamin D3 (25(OH)D3) and the active 1,25-dihydrovitamin D3 (1,25(OH)2D3) in a cohort of non-obese women. METHODS: 58 female participants (age 31.9 ± 4.6 years; BMI 25.7 ± 3.7 kg/m2) had seven indicator PCBs [PCB28, PCB52, PCB101, PCB118, PCB138, PCB153 and PCB180] measured using high resolution gas chromatography, with total PCB level calculated. 25(OH)D3 and 1,25(OH)2D3 levels were determined by isotope-dilution liquid chromatography tandem mass spectrometry. RESULTS: In this cohort, vitamin D3 (25(OH)D3) and 1,25(OH)2D3 levels were 50.7 ± 25.3 nmol/L and 0.05 ± 0.02 ng/ml, respectively. Of those, 28 had vitamin D deficiency [25(OH)D3 level <20 ng/ml (<50nmol/)]. Total PCBs correlated positively with total group 25(OH)D3 (r = 0.22, p = 0.04) as did PCB118 (r = 0.25, p = 0.03). Total PCBs did not correlate with total group 1,25(OH)2D3; however, PCB180 did correlate positively with 1,25(OH)2D3 (r = 0.34, p = 0.03) as did PCB153 (r = 0.33, p < 0.03), with PCB 28 correlating negatively (r = -0.29, p < 0.04). In the vitamin D deficient subgroup, total PCBs, PCB153 and PCB180 positively correlated with 25(OH)D3 (p < 0.05). Multilinear regression analysis indicated all associations could be accounted for by BMI. CONCLUSION: Though certain PCBs associated with 25(OH)D3 and 1,25(OH)2D3, all associations could be accounted for by BMI. This study therefore indicates that the deleterious effects from PCB accumulation are not mediated by effects on 25(OH)D3 or 1,25(OH)2D3.

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

BACKGROUND: Perfluorinated alkyl acids (PFAAs) are persistent organic pollutants affected by BMI and ethnicity, with contradictory reports of association with vitamin D deficiency. METHODS: Twenty-nine Caucasian women with non-obese polycystic ovary syndrome (PCOS) and age- and BMI-matched Caucasian control women (n = 30) were recruited. Paired serum samples were analyzed for PFAAs (n = 13) using high-performance liquid chromatography-tandem mass spectrometry. Tandem mass spectrometry determined levels of 25(OH)D3 and the active 1,25(OH)2D3. RESULTS: Women with and without PCOS did not differ in age, weight, insulin resistance, or systemic inflammation (C-reactive protein did not differ), but the free androgen index was increased. Four PFAAs were detected in all serum samples: perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS). Serum PFOS was higher in PCOS versus controls (geometric mean [GM] 3.9 vs. 3.1 ng/mL, p < 0.05). Linear regression modeling showed that elevated PFHxS had higher odds of a lower 25(OH)D3 (OR: 2.919, 95% CI 0.82-5.75, p = 0.04). Vitamin D did not differ between cohorts and did not correlate with any PFAAs, either alone or when the groups were combined. When vitamin D was stratified into sufficiency (>20 ng/mL) and deficiency (<20 ng/mL), no correlation with any PFAAs was seen. CONCLUSIONS: While the analyses and findings here are exploratory in light of relatively small recruitment numbers, when age, BMI, and insulin resistance are accounted for, the PFAAs do not appear to be related to 25(OH)D3 or the active 1,25(OH)2D3 in this Caucasian population, nor do they appear to be associated with vitamin D deficiency, suggesting that future studies must account for these factors in the analysis.

Relationship between endocrine disrupting chemicals (phthalate metabolites, triclosan and bisphenols) and vitamin D in female subjects: An exploratory pilot study.

INTRODUCTION: Evidence suggests that endocrine disrupting chemicals (EDCs), commonly used in plastics and personal care products, may be associated with reduced levels of vitamin D. Therefore, this study examined the relationship between phthalate metabolites, 5-chloro-2-(2,4-dichlorophenoxy)phenol (triclosan; TCS) and bisphenols (BPs) with vitamin D3 (25(OH)D3) and active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and their relationship to calcium homeostasis. METHODS: 57 female participants (age 31.8 ± 4.6 years; BMI 25.6 ± 3.7 kg/m2) were analyzed for urinary levels of phthalate metabolites, TCS and BPs, and serum levels of 25(OH)D3 and 1,25(OH)2D3, determined by isotope-dilution liquid chromatography tandem mass spectrometry. Serum calcium/calmodulin-dependent (CaM) associated proteins were determined by Slow Off-rate Modified Aptamer (SOMA)-scan. RESULTS: In the study cohort, 25(OH)D3 and 1,25(OH)2D3 levels were 22.9 ± 11.2 ng/mL and 0.05 ± 0.02 ng/mL, respectively: mono-3-carboxypropyl-phthalate (MCPP) correlated negatively with 25(OH)D3 (ρ = -0.53, p = 0.01). 28 of the 57 women recruited were 25(OH)D3 deficient, <20 ng/mL (50 nmol/L): in this group, mono-iso-butylphthalate (MiBP) and mono-butylphthalate (MBP) negatively correlated with 25(OH)D3; (ρ = -0.47, p = 0.049) and (ρ = -0.64, p = 0.005), respectively. EDCs did not correlate with 1,25(OH)2D3, measures of renal function or CaM proteins. CONCLUSION: These putative data indicate that MCPP is related to 25(OH)D3, while MiBP and MBP were related to vitamin D deficiency; however, no correlations were observed with TCS and BPs. No phthalate metabolites correlated with 1,25(OH)2D3, CaM associated proteins or renal function, suggesting that effects occur earlier in the vitamin D pathway and not through modulation of cellular calcium flux. The observed correlations are surprisingly strong compared to other predictors of 25(OH)D3, and larger studies adjusting for potential confounders are warranted.

Association of flame retardants, polybrominated diethyl ethers (PBDEs), with vitamin D in female subjects.

INTRODUCTION: A class of flame retardants, polybrominated diethyl ethers (PBDEs), are known endocrine disrupters and may induce the hepatic enzymes CYP24 and CYP3A that promote 25-hydroxylation of vitamin D3. Therefore, this study examined the association of PBDEs with vitamin D3 (25(OH)D3) and the active 1,25-dihydrovitamin D3 (1,25(OH)2D3) in a cohort of non-obese women. METHODS: 58 female participants (age:31.9 ± 4.6 years; body mass index (BMI):25.7 ± 3.7 kg/m2) had seven indicator PBDEs [PBDE28; PBDE47; PBDE99; PBDE100; PBDE153; PBDE154; PBDE183] measured using high resolution gas chromatography, with Æ©PBDE level calculated. 25(OH)D3 and 1,25(OH)2D3 levels were determined by isotope-dilution liquid chromatography tandem mass spectrometry. Plasma level of calcium/calmodulin-dependent protein kinase type 1 (CaMK1) was measured by Somascan proteomics. RESULTS: In this cohort, vitamin D3 (25(OH)D3) and 1,25(OH)2D3 levels were 22.9 ± 11.2 ng/mL and 0.05 ± 0.02 ng/mL, respectively. Of those, 28 had vitamin D deficiency [25(OH)D3 level <20 ng/mL (<50 nmol/L)]. For the whole group, individual PBDEs (PBDE28; PBDE47; PBDE99; PBDE100; PBDE153; PBDE154; PBDE183) and Æ©PBDEs did not correlate with 25(OH)D3 or its active metabolite 1,25(OH)2D3 nor with BMI. For the subset who were 25(OH)D3 sufficient, negative correlations were found for 1,25(OH)2D3 with PBDE153 (ρ = -0.77; p = 0.02) and PBDE100 (ρ = -0.72; p = 0.005). In the subset of women who were 25(OH)D3 deficient, positive correlations were found for 1,25(OH)2D3 with PBDE153 (ρ = 0.68; p = 0.02) and Æ©PBDEs (ρ = 0.57; p = 0.03). Using sufficient and deficient subset categories, no correlations were seen with 25(OH)D3 nor any of the PBDEs, and PBDEs did not correlate to renal function (estimated glomerular filtration rate, eGFR). 1,25(OH)2D3 was negatively associated with CaMK1 (r = -0.36; p = 0.03) as was PBDE153 (r = -0.31; p = 0.02). CONCLUSION: PBDEs were not associated with 25(OH)D3, but PBDE100 and 153 correlated with its active 1,25(OH)2D3 metabolite and PBDE153 correlated to the calcium modulator CaMKI, suggesting that PBDE effects could either be mediated through vitamin D status or that functional inactivation or inhibition of 1,25(OH)2D3 may contribute to the impact of vitamin D deficiency.

Association between Organochlorine Pesticides and Vitamin D in Female Subjects.

In human population studies, organochlorine pesticides (OCPs) have been linked to vitamin D deficiency. Therefore, this study examined the association between OCPs, vitamin D3 (cholecalciferol, 25(OH)D3), and the active metabolite 1,25-dihydrovitamin D3 (1,25(OH)2D3) in a cohort of non-obese women. The serum samples of 58 female participants (age-31.9 ± 4.6 years; body mass index (BMI)-25.7 ± 3.7 kg/m2) were screened for 10 indicator OCPs. 25(OH)D3 and 1,25(OH)2D3 levels were determined via isotope dilution liquid chromatography tandem mass spectrometry. In this cohort, the 25(OH)D3 and 1,25(OH)2D3 levels were 22.9 ± 11.2 ng/mL and 0.05 ± 0.02 ng/mL, respectively, with 28 participants classified as 25(OH)D3-deficient (<50 nmol/L). In the study cohort, no correlations were found between individual or total OCPs (Æ©OCPs) and 25(OH)D3. p,p'-dichlorodiphenyldichloroethylene (DDE) and Æ©OCPs correlated positively with 1,25(OH)2D3, with the latter being negatively correlated with estimated glomerular filtration rate (eGFR). In women with sufficient 25(OH)D3 levels, p,p'-dichlorodiphenyltrichloroethan (DDT) was positively correlated with 1,25(OH)2D3, whilst in the deficient group, hexachlorobenzene (HCB) and p,p'-(DDE) were positively correlated with 1,25(OH)2D3, ß-Hexachlorocyclohexane (HCH) was positively correlated with 25(OH)D3, and none of the OCPs were associated with measures of renal function. Overall, OCPs and Æ©OCPs were not associated with 25(OH)D3, suggesting that they are unrelated to vitamin D deficiency, but p,p'-DDE and Æ©OCPs correlated positively with active 1,25(OH)2D3, while Æ©OCPs correlated negatively with eGFR, suggesting a possible renal effect. Analysis of vitamin D deficiency revealed an association between ß-HCH and 25(OH)D3, and between HCB and p,p'-DDE and 1,25(OH)2D3, suggesting that OCP effects may be enhanced in cases of vitamin D deficiency.

Serum polychlorinated biphenyl levels and circulating miRNAs in non-obese women with and without polycystic ovary syndrome.

Introduction: Polychlorinated biphenyls (PCBs), organic lipophilic pollutants that accumulate through diet and increase with age, have been associated with polycystic ovary syndrome (PCOS) and shown to affect microRNA (miRNA) expression. This work aimed to determine if PCBs were associated with circulating miRNAs and whether there were any correlations with serum PCB/miRNA levels and hormonal changes. Methods: 29 non-obese PCOS and 29 healthy control women, with similar age and body mass index (BMI), had their serum miRNAs measured together with 7 indicator PCBs (PCB28, PCB52, PCB101, PCB118, PCB138, PCB153, PCB180) using high resolution gas chromatography coupled with high resolution mass spectrometry. Results: In the combined study cohort, four miRNAs (hsa-miR-139-5p, hsa-miR-424-5p, hsa-miR-195-5p, hsa-miR-335-5p) correlated with PCBs, but none correlated with metabolic parameters. hsa-miR-335-5p correlated with FSH. When stratified, 25 miRNAs correlated with PCBs in controls compared to only one (hsa-miR-193a-5p) in PCOS; none of these miRNAs correlated with the metabolic parameters of BMI, insulin resistance, or inflammation (C-reactive protein, CRP). However, of these 25 miRNAs in controls, hsa-miR-26a-5p, hsa-miR-193a-5p, hsa-miR-2110 and hsa-miR-195-5p positively correlated with luteinizing hormone (LH), hsa-miR-99b-5p and hsa-miR-146b-5p correlated with estradiol, hsa-miR-193a-5p correlated with progesterone, hsa-miR-195-5p correlated with follicle stimulating hormone (FSH), and hsa-miR-139-5p and hsa-miR-146b-5p negatively correlated with anti-müllerian hormone (AMH) (all p<0.05). hsa-miR-193a-5p in PCOS cases correlated with estradiol. Conclusion: In this cohort of women, with no difference in age and BMI, and with similar PCB levels, the miRNAs correlating to PCBs associated with menstrual cycle factors in healthy menstruating controls versus the anovulatory PCOS subjects. The PCB-associated miRNAs did not correlate with non-reproductive hormonal and metabolic parameters. This suggests that PCB effects on miRNAs may result in changes to the hypothalamo-ovarian axis that may thus affect fertility.

Exploration of the correlation of serum polychlorinated biphenyl levels with luteal phase hormonal parameters and infertility in women with or without polycystic ovary syndrome.

Introduction: Polychlorinated biphenyls (PCBs) are organic lipophilic pollutants that accumulate in the body. Previous research has linked PCBs with menstrual function; therefore, this study was undertaken to investigate the correlation of PCBs with luteal phase hormonal parameters of menstrual function at day 21 in a group of non-obese women prior to in vitro fertilization (IVF). Methods: Fifty-eight non-obese Caucasian women from a UK academic center, 29 with polycystic ovary syndrome (PCOS) and 29 without, were recruited. PCOS women all had anovulatory infertility. Non-PCOS women: five with unexplained infertility, the remainder with male factor infertility (n=14) or tubal problems (n=10). Blood was withdrawn at day 21 of the menstrual cycle for non-PCOS women, at the time of mock embryo transfer. PCBs were measured using high resolution gas chromatography. Results: Only PCB118, PCB153, PCB138 and PCB180 were detected in all samples, and levels did not differ between PCOS and non-PCOS subjects. In non-PCOS subjects, PCB153, PCB138 and PCB180 inversely correlated with estradiol (p<0.05); PCB118 and PCB138 inversely correlated with follicle stimulating hormone (FSH) (p<0.05); PCB118 (p<0.05), PCB153, PCB138 and PCB180 (all p<0.01) inversely correlated with luteinizing hormone (LH). Control women without PCOS with unexplained infertility showed higher levels of PCB118, PCB153, PCB138 and PCB180 (p<0.05) compared to those control women without PCOS with tubal or male factor infertility, though other hormonal parameters did not differ other than that FSH that was lower in the unexplained group (p=0.01). The only correlation observed in PCOS women with anovulatory infertility was that between PCB180 and progesterone (p<0.05). Conclusion: PCBs correlated with luteal phase menstrual cycle hormones in control women without PCOS and may contribute to the mechanism of unexplained infertility; in PCOS women, no correlations of the PCBs were seen for estradiol, LH or FSH.

A case-control study of polychlorinated biphenyl association with metabolic and hormonal outcomes in polycystic ovary syndrome.

Polychlorinated biphenyls (PCBs) are a class of environmental pollutants with a long half-life that sequester in fat. Women with polycystic ovarian syndrome (PCOS) may represent a sensitive subgroup to endogenous exposure to PCBs because of associated weight gain. Seven PCB congeners were compared in age, ethnicity, and BMI matched women with (n = 29) and without (n = 30) PCOS and related to metabolic outcomes, and steroid and thyroid hormone levels. PCB118, PCB138, PCB153, and PCB180 were detected in all serum samples but geometric mean did not differ between cases and controls. PCBs correlated with increasing concentrations of each other (p < .01), increasing age (p < .01) and decreasing lneGFR (p < .05). lnPCB118 correlated with increasing Free-T4 (p = .028). lnPCB158, lnPCB180, and ln∑PCB correlated with increasing lnSHBG (p = .044). In regression modeling, although not significant, PCB118 positively associated with lnSHBG in controls (p = .0504) but not in cases; estradiol inversely associated with PCB138 in controls (p = .055) and ∑PCB in cases (p = .051). No significant associations were observed between metabolic endpoints, and steroid and thyroid hormone levels. The results presented do not suggest the PCOS cases in this cohort are at adverse risk compared to age, ethnicity, and BMI matched controls.

Psychological Impact of COVID-19, Isolation, and Quarantine: A Cross-Sectional Study.

PURPOSE: The COVID-19 pandemic has resulted in mandatory isolation and quarantine. The objective of this study was to describe and compare the psychological impacts of COVID-19 isolation and quarantine. METHODS: This was a cross-sectional retrospective study. Participants were Bahrainis aged >18 years who had undergone either isolation or quarantine. Eligible participants were identified from the COVID-19 contacts (quarantine) and cases (isolation) database of Bahrain. Validated questionnaires for self-reported depression (Center for Epidemiological Studies - depression [CES-D]), posttraumatic stress (Impact of Event Scale - revised [IES-R]), and perceived stigma (Stigma Scale [SS]) were administered. RESULTS: Mean CES-D, IES-R, and SS scores were 16.76±5.65, 13.50±14.67, and 25.29±7.99, respectively. In sum, 40% (205 of 502) of participants showed clinically significant depression, and <20% (98 of 502) had indications of some posttraumatic distress, with greater depression and distress in those isolated than those quarantined. Perceived stigma was reported by 53.4% (268 of 502) of participants, more prominent among those quarantined. Depression and posttraumatic stress scores were significantly higher in females, college students, those with a history of mental health conditions, knowing a COVID-19 fatality, and experiencing social conflict. Age was a significant variable correlated with all three scales, with younger participants indicating more distress, depression, and stigma. Duration of segregation was significantly correlated with CES-D, score showing more depressive symptoms as the duration of isolation increased. Significant predictors were age, sex, history of mental illness, and COVID-19 status. CONCLUSION: Isolated and quarantined individuals reported depression, perceived stigma, and to a lesser extent distress. Psychological interventions identifying and targeting people with different-severity psychological burdens are in urgent need.