Exposure to the pesticides linuron, dimethomorph and imazalil alters steroid hormone profiles and gene expression in developing rat ovaries.

Inhibition of androgen signaling during critical stages of ovary development can disrupt folliculogenesis with potential consequences for reproductive function later in life. Many environmental chemicals can inhibit the androgen signaling pathway, which raises the question if developmental exposure to anti-androgenic chemicals can negatively impact female fertility. Here, we report on altered reproductive hormone profiles in prepubertal female rats following developmental exposure to three pesticides with anti-androgenic potential: linuron (25 and 50 mg/kg bw/d), dimethomorph (60 and 180 mg/kg bw/d) and imazalil (8 and 24 mg/kg bw/d). Dams were orally exposed from gestational day 7 (dimethomorph and imazalil) or 13 (linuron) until birth, then until end of dosing at early postnatal life. Linuron and dimethomorph induced dose-related reductions to plasma corticosterone levels, whereas imazalil mainly suppressed gonadotropin levels. In the ovaries, expression levels of target genes were affected by linuron and dimethomorph, suggesting impaired follicle growth. Based on our results, we propose that anti-androgenic chemicals can negatively impact female reproductive development. This highlights a need to integrate data from all levels of the hypothalamic-pituitary-gonadal axis, as well as the hypothalamic-pituitary-adrenal axis, when investigating the potential impact of endocrine disruptors on female reproductive development and function.

Use of candles and risk of cardiovascular and respiratory events in a Danish cohort study.

Burning candles at home emit small particles and gases that pollute indoor air. Exposure to fine particles in outdoor air has been convincingly linked to cardiovascular and respiratory events, while the associations with fine and ultrafine particles from candle burning remain unexplored. We examined the association between the use of candles and incident cardiovascular and respiratory events. We collected data on 6757 participants of the Copenhagen Aging and Midlife Biobank cohort recruited in 2009 and followed them up for the first hospital contact for incident cardiovascular and respiratory events until 2018. We investigated an association between the self-reported frequency of candle use in wintertime and cardiovascular and respiratory events, using Cox regression models adjusting for potential confounders. During follow-up, 1462 and 834 were admitted for cardiovascular and respiratory events, respectively. We found null associations between candle use and a hospital contact due to cardiovascular and respiratory events, with hazard ratios (HRs) and 95% confidence intervals (CI) of 0.97 (95% CI: 0.84, 1.11) and 0.98 (95% CI: 0.81, 1.18), respectively, among those using candles >4 times/week compared with <1 time/week. For cause-specific cardiovascular diseases, HRs were 1.10 (95% CI: 0.85, 1.43) for ischemic heart disease and 1.18 (95% CI: 0.77, 1.81) for myocardial infarction. For chronic obstructive pulmonary disease, HR was 1.26 (95% CI: 0.81, 1.97). We found no statistically significant associations between candle use and the risk of cardiovascular and respiratory events. Studies with improved exposure assessments are warranted.

Long-Term Exposure to Road Traffic Noise and Air Pollution, and Incident Atrial Fibrillation in the Danish Nurse Cohort.

BACKGROUND: Associations between long-term exposure to air pollution and road traffic noise have been established for ischemic heart disease, but findings have been mixed for atrial fibrillation (AF). OBJECTIVES: The goal of the study was to examine associations of long-term exposure to road traffic noise and air pollution with AF. METHODS: Time-varying Cox regression models were used to estimate associations of 1-, 3-, and 23-y mean road traffic noise and air pollution exposures with AF incidence in 23,528 women enrolled in the Danish Nurse Cohort (age >44y at baseline in 1993 or 1999). AF diagnoses were ascertained via the Danish National Patient Register. Annual mean weighted 24-h average road traffic noise levels (Lden) at the nurses' residences, since 1970, were estimated using the Nord2000 model, and annual mean levels of particulate matter with a diameter <2.5µm (PM2.5) and nitrogen dioxide (NO2) were estimated using the DEHM/UBM/AirGIS model. RESULTS: Of 23,528 nurses with no prior AF diagnosis at the cohort baseline, 1,522 developed AF during follow-up. In a fully adjusted model (including PM2.5), the estimated risk of AF was 18% higher [hazard ratio (HR); 95% confidence interval (CI): 1.18; 1.02, 1.36] in nurses with residential 3-y mean Lden levels >58 dB vs. <48 dB, with similar findings for 1-y mean exposures. A 3.9-µg/m3 increase in 3-y mean PM2.5 was associated with incident AF before and after adjustment for concurrent exposure to road traffic noise (HR 1.09; 95% CI: 1.00, 1.20 and 1.08; 95% CI: 0.97, 1.19, respectively). Associations with 1-y mean PM2.5 exposures were positive but closer to the null and not significant. Associations with NO2 were null for all time periods before and after adjustment for road traffic noise and inverse when adjusted for concurrent PM2.5. CONCLUSION: Our analysis of prospective data from a cohort of Danish female nurses followed for up to 14 y provided suggestive evidence of independent associations between incident AF and 1- and 3-y exposures to road traffic noise and PM2.5. https://doi.org/10.1289/EHP8090.

Perinatal exposure to known endocrine disrupters alters ovarian development and systemic steroid hormone profile in rats.

Disrupted ovarian development induced by chemical exposure may impair fertility later in life. Since androgens are essential for early ovarian development, we speculated that perinatal exposure to a binary mixture of the known anti-androgens DEHP and procymidone could alter steroid synthesis, disrupt ovarian follicle recruitment and ultimately maturation in female rat offspring. Wistar rat dams were exposed by oral gavage from gestation day 7 to postnatatal day 22 to two mixture doses known to alter reproductive development in male offspring (low: 10 mg/kg bw/day of procymidone and 30 mg/kg bw/day of DEHP; high: 20 mg/kg bw/day of procymidone and 60 mg/kg bw/day of DEHP). The Effects on plasma steroid hormones, ovarian follicle distribution and expression of markers related to steroid synthesis were examined in female offspring. In prepubertal offspring, we observed an increased number of newly recruited (primary) follicles in exposed animals compared to controls, and the plasma steroid hormone profile was altered by exposure: levels of progesterone, corticosterone and estrone were dose dependently elevated, whereas androgen levels were unaffected. In adulthood, a trend towards a smaller number of early-stage follicles may point to accelerated loss of follicle reserves, which is disconcerting. The changes in follicle distribution in exposed ovaries may reflect the combined influence of androgen receptor antagonism and altered ovarian steroid synthesis. This study adds to a growing body of evidence showing altered ovarian development following exposure to human relevant chemicals with possible severe consequences for female fertility.

Long-term exposure to road traffic noise and incident myocardial infarction: A Danish Nurse Cohort study.

BACKGROUND: Evidence of nonauditory health effects of road traffic noise exposure is growing. This prospective cohort study aimed to estimate the association between long-term exposure to road traffic noise above a threshold and incident myocardial infarction (MI) in Denmark. METHODS: In the Danish Nurse Cohort study, we used data of 22,378 women, at recruitment in 1993 and 1999, who reported information on MI risk factors. The participants' first hospital contact or out-of-hospital death due to MI were followed-up until 2014. We investigated a relationship between residential exposures to road traffic noise levels (Lden) up to 23 years and incident MI (overall, nonfatal, and fatal) using time-varying Cox regression models adjusting for potential confounders and air pollutants. We estimated thresholds of road traffic noise (53, 56, and 58 dB) associated with incident MI in a piece-wise linear regression model. RESULTS: Of the 22,378 participants, 633 developed MI, 502 of which were nonfatal. We observed a non-linear relationship between the 23-year running mean of Lden and incident MI with a threshold level of 56 dB, above which hazard ratios (95% confidence intervals) were 1.30 (0.97, 1.75) for overall and 1.46 (1.05, 2.03) for nonfatal MI per 10 dB. The association with nonfatal MI attenuated slightly to 1.34 (0.95, 1.90) after adjustment for fine particles. CONCLUSIONS: We found that long-term exposure to road traffic noise above 56 dB may increase the risk of MI. The study findings suggest that road traffic noise above 56 dB may need regulation in addition to the regulation of ambient pollutants.

Long-Term Exposure to Air Pollution and Incidence of Myocardial Infarction: A Danish Nurse Cohort Study.

BACKGROUND: Air pollution exposure has been linked to coronary heart disease, although evidence on PM2.5 and myocardial infarction (MI) incidence is mixed. OBJECTIVES: This prospective cohort study aimed to investigate associations between long-term exposure to air pollution and MI incidence, adjusting for road traffic noise. METHODS: We used data from the nationwide Danish Nurse Cohort on 22,882 female nurses (>44 years of age) who, at recruitment in 1993 or 1999, reported information on cardiovascular disease risk factors. Data on MI incidence was collected from the Danish National Patient Register until the end of 2014. Annual mean concentrations of particulate matter (PM) with a diameter <2.5 µg/m3 (PM2.5), PM10, nitrogen dioxide (NO2), and nitrogen oxides (NOx) at the nurses' residences since 1990 (PM10 and PM2.5) or 1970 (NO2 and NOx) were estimated using the Danish Eulerian Hemispheric Model/Urban Background Model/AirGIS (DEHM/UBM/AirGIS) dispersion model. We used time-varying Cox regression models to examine the association between 1- and 3-y running means of these pollutants, as well as 23-y running means of NO2 and NOx, with both overall and fatal incident MI. Associations were explored in three progressively adjusted models: Model 1, adjusted for age and baseline year; Model 2, with further adjustment for potential confounding by lifestyle and cardiovascular disease risk factors; and Model 3, with further adjustment for road traffic noise, modeled as the annual mean of a weighted 24-h average (Lden). RESULTS: Of the 22,882 women, 641 developed MI during a mean follow-up of 18.6 y, 121 (18.9%) of which were fatal. Reported hazard ratios (HRs) were based on interquartile range increases of 5.3, 5.5, 8.1, and 11.5 µg/m3 for PM2.5, PM10, NO2, and NOx, respectively. In Model 1, we observed a positive association between a 3-y running mean of PM2.5 and an overall incident MI with an HR= 1.20 (95% CI: 1.07, 1.35), which attenuated to HR= 1.06 (95% CI: 0.92, 1.23) in Model 2. In Model 1 for incident fatal MI, we observed a strong association with a 3-y running mean of PM2.5, with an HR= 1.69 (95% CI: 1.33, 2.13), which attenuated to HR= 1.35 (95% CI: 1.01, 1.81) in Model 2. Similar associations were seen for PM10, with 3-y, Model 2 estimates for overall and fatal incident MI of HR= 1.06 (95% CI: 0.91, 1.23) and HR= 1.35 (95% CI: 1.01, 1.81), respectively. No evidence of an association was observed for NO2 or NOx. For all pollutants, associations in Model 2 were robust to further adjustment for road traffic noise in Model 3 and were similar for a 1-y running mean exposure. CONCLUSIONS: We found no association between long-term exposure to PM2.5, PM10, NO2, or NOx and overall MI incidence, but we observed positive associations for PM2.5 and PM10 with fatal MI. We present novel findings that the association between PM and MI incidence is robust to adjustment for road traffic noise. https://doi.org/10.1289/EHP5818.

Road traffic noise and markers of adiposity in the Danish Nurse Cohort: A cross-sectional study.

BACKGROUND: Studies have suggested that traffic noise is associated with markers of obesity. We investigated the association of exposure to road traffic noise with body mass index (BMI) and waist circumference in the Danish Nurse Cohort. METHODS: We used data on 15,501 female nurses (aged >44 years) from the nationwide Danish Nurse Cohort who, in 1999, reported information on self-measured height, weight, and waist circumference, together with information on socioeconomic status, lifestyle, work and health. Road traffic noise at the most exposed façade of the residence was estimated using Nord2000 as the annual mean of a weighted 24-h average (Lden). We used multiple linear regression models to examine associations of road traffic noise levels in 1999 (1-year mean) with BMI and waist circumference, adjusting for potential confounders, and evaluated effect modification by degree of urbanization, air pollution levels, night shift work, job strain, sedative use, sleep aid use, and family history of obesity. RESULTS: We did not observe associations between road traffic noise (per 10 dB increase in the 1-year mean Lden) and BMI (kg/m2) (ß: 0.00; 95% confidence interval (CI): -0.07, 0.07) or waist circumference (cm) (ß: -0.09; 95% CI: -0.31, 0.31) in the fully adjusted model. We found significant effect modification of job strain and degree of urbanization on the associations between Lden and both BMI and waist circumference. Job strained nurses were associated with a 0.41 BMI-point increase, (95% CI: 0.06, 0.76) and a 1.00 cm increase in waist circumference (95% CI: 0.00, 2.00). Nurses living in urban areas had a statistically significant positive association of Lden with BMI (ß: 0.26; 95% CI: 0.11, 0.42), whilst no association was found for nurses living in suburban and rural areas. CONCLUSION: Our results suggest that road traffic noise exposure in nurses with particular susceptibilities, such as those with job strain, or living in urban areas, may lead to increased BMI, a marker of adiposity.