Maternal exposure to UV filters:Associations with maternal thyroid hormones, IGF-I/IGFBP3 and birth outcomes

Background: Several chemical UV filters/absorbers ('UV filters' hereafter) have endocrine-disrupting properties in vitro and in vivo. Exposure to these chemicals, especially during prenatal development, is of concern. Objectives: To examine maternal exposure to UV filters, associations with maternal thyroid hormone, with growth factor concentrations as well as to birth outcomes. Methods: Prospective study of 183 pregnant women with 2nd trimester serum and urine samples available. Maternal concentrations of the chemical UV filters benzophenone-1 (BP-1) and benzophenone-3 (BP-3) in urine and 4-hydroxy-benzophenone (4-HBP) in serum were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The relationships between 2nd trimester maternal concentrations of the three chemical UV filters and maternal serum concentrations of thyroid hormones and growth factors, as well as birth outcomes (weight, height, and head and abdominal circumferences) were examined. Results: Positive associations between maternal serum concentrations of 4-HBP and triiodothyronine (T3), thyroxine (T4), insulin-like growth factor I (IGF-I) and its binding protein IGFBP3 were observed in mothers carrying male fetuses. Male infants of mothers in the middle 4-HBP exposure group had statistically significantly lower weight and shorter head and abdominal circumferences at birth compared to the low exposure group. Conclusions: Widespread exposure of pregnant women to chemical UV filters and the possible impact on maternal thyroid hormones and growth factors, and on fetal growth, calls for further studies on possible long-term consequences of the exposure to UV filters on fetal development and children’s health

Serum Testosterone Levels in 3-Month-Old Boys Predict Their Semen Quality as Young Adults

ContextIt remains unknown how the postnatal activation of the hypothalamic-pituitary-gonadal axis in infancy, also known as "minipuberty", relates to adult testis function.ObjectiveTo investigate how markers of reproductive function in 3-month-old boys correlate with adult reproductive health parameters.MethodsThis population-based birth cohort study (the Copenhagen Mother-Child cohort), conducted at Copenhagen University Hospital, Denmark, included 259 boys examined once around 3 months of age and again at 18 to 20 years. Reproductive hormones, penile length, testis volume, and semen quality were analyzed. Minipubertal markers of testis function (by tertiles, T1-T3) were explored as predictors of adult semen quality using linear regression models. Associations between reproductive outcomes in infancy and young adulthood were estimated by intraclass correlation coefficients (ICCs), describing how well measurements in infancy correlate with those in adulthood.ResultsSerum testosterone concentration in infancy was positively associated with adult total sperm count. Median (IQR) total sperm count was 84 (54-138) million spermatozoa for boys in T1, 141 (81-286) million spermatozoa in T2, and 193 (56-287) million spermatozoa in T3. We found the highest ICC for FSH (0.41; 95% CI, 0.26-0.57), while ICCs for inhibin B, SHBG, penile length, and testis volume ranged between 0.24 and 0.27. ICCs for LH and for total and free testosterone were lower and statistically nonsignificant.ConclusionSerum testosterone in infancy was a predictor of adult total sperm count. Other reproductive hormones and genital measures showed good correlation between infancy and adulthood, suggesting that an individual's reproductive setpoint starts shortly after birth in boys and persists until adulthood.</p

Reproductive hormones, bone mineral content, body composition, and testosterone therapy in boys and adolescents with Klinefelter syndrome

Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.9–20.6 years. Serum concentrations of total testosterone and inhibin B were low, whereas luteinizing hormone and follicle-stimulating hormone were high in patients before TRT. Despite normal body mass index, body fat percentage and the ratio between android fat percentage and gynoid fat percentage were significantly higher in the entire group irrespective of tr eatment status. In patients evaluated before and during TRT, a tendency toward a more benefi cial body composition with a significant reduction in the ratio between android fat pe rcentage and gynoid fat percentage during TRT was found. Bone mineral content (BMC) did not differ from the reference, but BMC corrected for bone area was significantly low er when compared to the reference. This study confirms that patients with KS have an unf avorable body composition and an impaired bone mineral status already during childhood and adolescence. Systematic studies are needed to evaluate whether TRT during puberty will improve these parameters

Prenatal and Perinatal Risk Factors for Autism in China

We conducted a case–control study using 190 Han children with and without autism to investigate prenatal and perinatal risk factors for autism in China. Cases were recruited through public special education schools and controls from regular public schools in the same region (Tianjin), with frequency matching on sex and birth year. Unadjusted analyses identified seven prenatal and seven perinatal risk factors significantly associated with autism. In the adjusted analysis, nine risk factors showed significant association with autism: maternal second-hand smoke exposure, maternal chronic or acute medical conditions unrelated to pregnancy, maternal unhappy emotional state, gestational complications, edema, abnormal gestational age (<35 or >42 weeks), nuchal cord, gravidity >1, and advanced paternal age at delivery (>30 year-old)

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference