Puberty is an important period of life with marked physical and psychological changes. Subsequent to the reactivation of the hypothalamus-pituitary-gonadal axis after a period of quiescence during childhood, the hormonal changes during this transitional period ultimately lead to attainment of complete adult reproductive capacity. The precise mechanisms underlying the reactivation of the hypothalamus-pituitary-gonadal axis are not fully known; however, genetic, nutritional, stress-related, and environmental factors are known to influence the onset of puberty.¹

More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p′-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04–1.74). The data did not indicate that this increased risk was driven by any specific disorder. The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure–response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure–outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field.

Rationale: Exposure to particulate matter is associated with risk of cardiovascular events, possibly through endothelial dysfunction, and indoor air may be most important. Objectives: We investigated effects of controlled exposure to indoor air particles on microvascular function (MVF) as the primary endpoint and biomarkers of inflammation and oxidative stress as secondary endpoints in a healthy elderly population. Methods: A total of 21 nonsmoking couples participated in a randomized, double-blind, crossover study with two consecutive 48-hour exposures to either particle-filtered or nonfiltered air (2,533–4,058 and 7,718–12,988 particles/cm³, respectively) in their homes. Measurements and Main Results: MVF was assessed noninvasively by measuring digital peripheral artery tone after arm ischemia. Secondary endpoints included hemoglobin, red blood cells, platelet count, coagulation factors, P-selectin, plasma amyloid A, C-reactive protein, fibrinogen, IL-6, tumor necrosis factor-α, protein oxidation measured as 2-aminoadipic semialdehyde in plasma, urinary 8-iso-prostaglandin F_2α, and blood pressure. Indoor air filtration significantly improved MVF by 8.1% (95% confidence interval, 0.4–16.3%), and the particulate matter (diameter < 2.5 μm) mass of the indoor particles was more important than the total number concentration (10–700 nm) for these effects. MVF was significantly associated with personal exposure to iron, potassium, copper, zinc, arsenic, and lead in the fine fraction. After Bonferroni correction, none of the secondary biomarkers changed significantly. Conclusions: Reduction of particle exposure by filtration of recirculated indoor air for only 48 hours improved MVF in healthy elderly citizens, suggesting that this may be a feasible way of reducing the risk of cardiovascular disease.

Background: Particulate matter, especially ultrafine particles (UFPs), may cause health effects through generation of oxidative stress, with resulting damage to DNA and other macromolecules. Objective: We investigated oxidative damage to DNA and related repair capacity in peripheral blood mononuclear cells (PBMCs) during controlled exposure to urban air particles with assignment of number concentration (NC) to four size modes with average diameters of 12, 23, 57, and 212 nm. Design: Twenty-nine healthy adults participated in a randomized, two-factor cross-over study with or without biking exercise for 180 min and with exposure to particles (NC 6169-15362/cm3) or filtered air (NC 91-542/cm3) for 24 hr. Methods: The levels of DNA strand breaks (SBs), oxidized purines as formamidopyrimidine DNA glycolase (FPG) sites, and activity of 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1) in PBMCs were measured by the Comet assay. mRNA levels of OGG1, nucleoside diphosphate linked moiety X-type motif 1 (NUDT1), and heme oxygenase-1 (HO1) were determined by real-time reverse transcriptase–polymerase chain reaction. Results: Exposure to UFPs for 6 and 24 hr significantly increased the levels of SBs and FPG sites, with a further insignificant increase after physical exercise. The OGG1 activity and expression of OGG1, NUDT1, and HO1 were unaltered. There was a significant dose–response relationship between NC and DNA damage, with the 57-nm mode as the major contributor to effects. Concomitant exposure to ozone, nitrogen oxides, and carbon monoxide had no influence. Conclusion: Our results indicate that UFPs, especially the 57-nm soot fraction from vehicle emissions, causes systemic oxidative stress with damage to DNA and no apparent compensatory up-regulation of DNA repair within 24 hr.