Air Pollution Exposures During Adulthood and Risk of Endometriosis in the Nurses’ Health Study II

Background: Particulate matter and proximity to large roadways may promote disease mechanisms, including systemic inflammation, hormonal alteration, and vascular proliferation, that may contribute to the development and severity of endometriosis. Objective: Our goal was to determine the association of air pollution exposures during adulthood, including distance to road, particulate matter < 2.5 μm, between 2.5 and 10 μm, and < 10 μm, (PM2.5, PM10–2.5, PM10), and timing of exposure with risk of endometriosis in the Nurses’ Health Study II. Methods: Proximity to major roadways and outdoor levels of PM2.5, PM10–2.5, and PM10 were determined for all residential addresses from 1993 to 2007. Multivariable-adjusted time-varying Cox proportional hazard models were used to estimate the relation between these air pollution exposures and endometriosis risk. Results: Among 84,060 women, 2,486 incident cases of surgically confirmed endometriosis were identified over 710,230 person-years of follow-up. There was no evidence of an association between endometriosis risk and distance to road or exposure to PM2.5, PM10–2.5, or PM10 averaged over follow-up or during the previous 2- or 4-year period. Conclusions: Traffic and air pollution exposures during adulthood were not associated with incident endometriosis in this cohort of women. Citation: Mahalingaiah S, Hart JE, Laden F, Aschengrau A, Missmer SA. 2014. Air pollution exposures during adulthood and risk of endometriosis in the Nurses’ Health Study II. Environ Health Perspect 122:58–64; http://dx.doi.org/10.1289/ehp.130662

Adult air pollution exposure and risk of infertility in the nurses' health study II

BACKGROUND: Exposures to air pollution has been associated with lower conception and fertility rates. However, the impact of pollution on infertility is unknown. OBJECTIVES: To examine the associations of roadway proximity (a measure of traffic exposure) and particulate matter (PM) air pollution and incidence of infertility. METHODS: Proximity to major roadways and ambient exposures to particulate matter less than 10 microns (PM10), between 2.5 and 10 microns (PM2.5-10), and less than 2.5 microns (PM2.5) were determined for all residential addresses for 36,294 members of the prospective Nurses' Health Study II cohort from 1993 to 2003. Infertility was defined by report of attempted conception for ≥12 months without success. Participants were able to report if evaluation was sought and if so, offer multiple clinical indications for infertility. Multivariable adjusted Cox proportional hazard models were used to estimate the relation between each exposure and infertility risk. RESULTS: Over 213,416 person-years, there were 2,508 incident reports of infertility. Results for overall infertility were inconsistent across exposure types. We observed a small increased risk in those living closer to compared to farther from a major road, multivariable adjusted hazard ratio (HR)=1.11(95% confidence interval (CI) = 1.02-1.20). Among those reporting primary infertility, risk was greater with closer distance to road and for all PM size fractions and exposure time windows. The multivariable adjusted HR (95%CI) for women living closer to compared to farther from a major road for primary infertility was 1.37 (1.22-1.52), while for secondary infertility HR=1.07 (0.95-1.21). In addition, the HR for every 10 mcg increase in cumulative PM2.5 among women with primary infertility was 1.61 (1.35-1.92), while it was 1.1 (0.91-1.33) for those with secondary infertility. CONCLUSIONS: This study suggests exposures to traffic and PM may be associated with a small increased risk of infertility, especially primary infertility

Bisphenol A exposure in Mexico City and risk of prematurity: a pilot nested case control study

Abstract Background Presence of Bisphenol A (BPA) has been documented worldwide in a variety of human biological samples. There is growing evidence that low level BPA exposure may impact placental tissue development and thyroid function in humans. The aim of this present pilot study was to determine urinary concentrations of BPA during the last trimester of pregnancy among a small subset of women in Mexico City, Mexico and relate these concentrations to risk of delivering prematurely. Methods A nested case-control subset of 60 participants in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) study in Mexico City, Mexico were selected based on delivering less than or equal to 37 weeks of gestation and greater than 37 weeks of gestation. Third trimester archived spot urine samples were analyzed by online solid phase extraction coupled with high performance liquid chromatography isotope dilution tandem mass spectrometry. Results BPA was detected in 80.0% (N = 48) of the urine samples; total concentrations ranged from &lt; 0.4 &#956;g/L to 6.7 &#956;g/L; uncorrected geometric mean was 1.52 &#956;g/L. The adjusted odds ratio of delivering less than or equal to 37 weeks in relation to specific gravity adjusted third trimester BPA concentration was 1.91 (95%CI 0.93, 3.91, p-value = 0.08). When cases were further restricted to births occurring prior to the 37th week (n = 12), the odds ratio for specific-gravity adjusted BPA was larger and statistically significant (p &lt; 0.05). Conclusions This is the first study to document measurable levels of BPA in the urine of a population of Mexican women. This study also provides preliminary evidence, based on a single spot urine sample collected during the third trimester, that pregnant women who delivered less than or equal to 37 weeks of gestation and prematurely (&lt; 37 weeks) had higher urinary concentrations of BPA compared to women delivering after 37 weeks.http://deepblue.lib.umich.edu/bitstream/2027.42/78251/1/1476-069X-9-62.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78251/2/1476-069X-9-62.pdfPeer Reviewe

Phenethyl isothiocyanate, a dual activator of transcription factors NRF2 and HSF1

Cruciferous vegetables are rich sources of glucosinolates which are the biogenic precursor molecules of isothiocyanates (ITCs). The relationship between the consumption of cruciferous vegetables and chemoprotection has been widely documented in epidemiological studies. Phenethyl isothiocyanate (PEITC) occurs as its glucosinolate precursor gluconasturtiin in the cruciferous vegetable watercress (Nasturtium officinale). PEITC has multiple biological effects, including activation of cytoprotective pathways, such as those mediated by the transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) and the transcription factor heat shock factor 1 (HSF1), and can cause changes in the epigenome. However, at high concentrations, PEITC leads to accumulation of reactive oxygen species and cytoskeletal changes, resulting in cytotoxicity. Underlying these activities is the sulfhydryl reactivity of PEITC with cysteine residues in its protein targets. This chemical reactivity highlights the critical importance of the dose of PEITC for achieving on target selectivity, which should be carefully considered in the design of future clinical trials

The real-world applications of the symptom tracking functionality available to menstrual health tracking apps

Purpose of review: The goal of this review was to evaluate whether the fields available in iOS mobile phone apps for recording menstrual cycle symptoms are able to be harmonized across platforms for potential use in research, such as aggregated data analysis. Recent findings: Symptom tracking capabilities are a common feature among menstrual health apps but have been the subject of limited investigations. Apps differ with respect to which symptoms are included and the rationale for these differences is unclear. Epidemiologic studies are poised to incorporate these data; however, a thorough exploration of symptom tracking functionality across apps is required. Summary: Our review finds that the language used to describe symptoms and the specificity with which symptoms are collected varies greatly across the most used iOS tracking apps. Although some apps allow numerical and qualitative description of symptoms, such as sleep and mood, most simply record the presence or absence of a symptom. Collaborative efforts between clinicians and researchers to guide what and how data is collected may allow tracking apps to realize their potential diagnostic applicability. Regardless, with the increasing use of menstrual health tracking apps, it is imperative that data retrieved from such apps can realize its potential in the research and clinical ecosystems

Temporal Variability and Predictors of Urinary Bisphenol A Concentrations in Men and Women

Background: Bisphenol A (BPA) is used to manufacture polymeric materials, such as polycarbonate plastics, and is found in a variety of consumer products. Recent data show widespread BPA exposure among the U.S. population.Objective Our goal in the present study was to determine the temporal variability and predictors of BPA exposure. Methods: We measured urinary concentrations of BPA among male and female patients from the Massachusetts General Hospital Fertility Center. Results: Between 2004 and 2006, 217 urine samples were collected from 82 subjects: 45 women (145 samples) and 37 men (72 samples). Of these, 24 women and men were partners and contributed 42 pairs of samples collected on the same day. Ten women became pregnant during the follow-up period. Among the 217 urine samples, the median BPA concentration was 1.20 μg/L, ranging from below the limit of detection (0.4 μg/L) to 42.6 μg/L. Age, body mass index, and sex were not significant predictors of urinary BPA concentrations. BPA urinary concentrations among pregnant women were 26% higher (–26%, +115%) than those among the same women when not pregnant (p > 0.05). The urinary BPA concentrations of the female and male partner on the same day were correlated (r = 0.36; p = 0.02). The sensitivity of classifying a subject in the highest tertile using a single urine sample was 0.64. Conclusion: We found a nonsignificant increase in urinary BPA concentrations in women while pregnant compared with nonpregnant samples from the same women. Samples collected from partners on the same day were correlated, suggesting shared sources of exposure. Finally, a single urine sample showed moderate sensitivity for predicting a subject’s tertile categorization

Utilizing a digital cohort to understand the health burden and lifestyle characteristics across the life course in individuals with polycystic ovary syndrome and possible PCOS

IntroductionPolycystic ovary syndrome (PCOS) is an ovulation disorder associated with multiple health conditions. This study analyzed health and lifestyle characteristics of those with diagnosed and possible PCOS in a large, digital cohort.MethodsWe analyzed data from female participants who enrolled in the Apple Women’s Health Study-a mobile-application-based cohort in the United States and provided informed consent from 11/14/2019–12/14/2024. Specific analyses were further restricted to those who responded to relevant survey questions. Self-reported sociodemographic, health (conditions and age at diagnosis), and lifestyle characteristics were evaluated, stratified by PCOS status: PCOS (self-reported physician diagnosed PCOS), possible PCOS (self-reported irregular menses and androgen excess), and no PCOS. Among those with PCOS/possible PCOS, we further evaluated potential predictors of not reporting a PCOS diagnosis using multivariable logistic regression.ResultsOf participants providing medical history at enrollment, 12.6% (n=11,022) reported PCOS, and among the subset without a PCOS diagnosis and with relevant survey data, 17.4% (n=7,152) were assigned possible PCOS. The median baseline age was 35 years. Most participants self-identified as non-Hispanic White (74.2%). The possible PCOS group was slightly less educated (≤high school: possible PCOS 14.5%, PCOS 17.3%, no PCOS 14.0%). The PCOS/possible PCOS groups reported lower socioeconomic status (SES) than the no PCOS group (low SES: PCOS 32.7%, possible PCOS 31.6%, no PCOS 23.5%). The PCOS and possible PCOS groups displayed a high burden of disease (cardiometabolic, endometrial hyperplasia/cancer, pregnancy complications, mental health conditions). Compared to those without PCOS, those with PCOS reported less healthy lifestyle behaviors relevant to physical activity/sleep/stress/smoking and more healthy lifestyle behaviors relevant to alcohol intake/diet. The age at diagnosis for multiple health conditions was earlier for participants with PCOS compared to those without PCOS. Young/old age (18 - 29/40–50 years), lower educational attainment, lower SES, and lower BMI were positive predictors of not reporting a PCOS diagnosis.ConclusionsThis study demonstrated significant differences in health and lifestyle characteristics across PCOS status (PCOS, possible PCOS, no PCOS), identifying populations that could benefit from early risk reduction counseling. Our results may inform discussions around clinical care models through improving awareness of health predictors and lifestyle interventions

Informative predictors of pregnancy after first IVF cycle using eIVF practice highway electronic health records

The aim of this study is to determine the most informative pre- and in-cycle variables for predicting success for a first autologous oocyte in-vitro fertilization (IVF) cycle. This is a retrospective study using 22,413 first autologous oocyte IVF cycles from 2001 to 2018. Models were developed to predict pregnancy following an IVF cycle with a fresh embryo transfer. The importance of each variable was determined by its coefficient in a logistic regression model and the prediction accuracy based on different variable sets was reported. The area under the receiver operating characteristic curve (AUC) on a validation patient cohort was the metric for prediction accuracy. Three factors were found to be of importance when predicting IVF success: age in three groups (38-40, 41-42, and above 42 years old), number of transferred embryos, and number of cryopreserved embryos. For predicting first-cycle IVF pregnancy using all available variables, the predictive model achieved an AUC of 68% + /- 0.01%. A parsimonious predictive model utilizing age (38-40, 41-42, and above 42 years old), number of transferred embryos, and number of cryopreserved embryos achieved an AUC of 65% + /- 0.01%. The proposed models accurately predict a single IVF cycle pregnancy outcome and identify important predictive variables associated with the outcome. These models are limited to predicting pregnancy immediately after the IVF cycle and not live birth. These models do not include indicators of multiple gestation and are not intended for clinical application.IIS-1914792 - National Science Foundation; N00014-19-1-2571 - Office of Naval Research Global; GM135930 - Office of Extramural Research, National Institutes of HealthPublished versio

PBRM1 Regulates Stress Response in Epithelial Cells

Polybromo1 (PBRM1) is a chromatin remodeler subunit highly mutated in cancer, particularly clear cell renal carcinoma. PBRM1 is a member of the SWI/SNF subcomplex, PBAF (PBRM1-Brg1/Brm-associated factors), and is characterized by six tandem bromodomains. Here we establish a role for PBRM1 in epithelial cell maintenance through the expression of genes involved in cell adhesion, metabolism, stress response, and apoptosis. In support of a general role for PBRM1 in stress response and apoptosis, we observe that loss of PBRM1 results in an increase in reactive oxygen species generation and a decrease in cellular viability under stress conditions. We find that loss of PBRM1 promotes cell growth under favorable conditions but is required for cell survival under conditions of cellular stress

Serum Concentrations of Polychlorinated Biphenyls in Relation to in Vitro Fertilization Outcomes

Background: Human exposure to polychlorinated biphenyls (PCBs) remains widespread. PCBs have been associated with adverse reproductive health outcomes including reduced fecundability and increased risk of pregnancy loss, although the human data remain largely inconclusive