Thyroid disruption in the lizard Podarcis bocagei exposed to a mixture of herbicides: a field study

Pesticide exposure has been related with thyroid disrupting effects in different vertebrate species. However, very little is known about the effects of these compounds in reptiles. In the Mediterranean area, lacertid lizards are the most abundant vertebrate group in agroecosystems, and have been identified as potential model species for reptile ecotoxicology. The aim of this study was to understand if the herbicides applied in corn fields have thyroid disruptive effects in the lizard Podarcis bocagei. Adult male lizards were captured in north-western Portugal in corn fields treated with herbicides (exposed sites), and in organic agricultural fields (reference sites). Thyroid and male gonad morphology and functionality, and testosterone levels were investigated through histological, immunohistochemical and biochemical techniques. Lizards from exposed locations displayed thyroid follicular lumens with more reabsorption vacuoles and significantly larger follicular area than those from reference fields. Furthermore, testes of lizards from exposed locations had significantly larger seminiferous tubule diameters, significantly higher number of spermatogenic layers and displayed an upregulation of thyroid hormone receptors when compared with lizards from reference areas. These findings strongly suggest that the complex mixture of herbicides that lizards are exposed to in agricultural areas have thyroid disrupting effects which ultimately affect the male reproductive system. Alachlor, which has demonstrated thyroid effects in mammals, may be largely responsible for the observed effects.We appreciate the assistance of Ricardo Valente and CIBIO members. All lizards were collected under a permit issued by the Instituto da Conservac¸a˜o daNatureza e Biodiversidade.This research and the technical position of R.C. Bicho was supported by FEDER through COMPETE-Programa Operacional Factores de Competitividade and National funding through FCT-Fundac¸a˜o para a Cieˆncia e Tecnologia, within the research project LAB-PET—Lacertid Lizards as Bioindicators of Pesticide Exposure and Toxicity in intensive market garden agriculture (FCT PTDC/AMB/64497/2006). M. J. Amaral benefited from a doctoral grant from FCT (SFRH/BD/31470/2006)

Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3

Age-related macular degeneration (AMD) is a leading cause of visual loss in Western populations. Susceptibility is influenced by age, environmental and genetic factors. Known genetic risk loci do not account for all the heritability. We therefore carried out a genome-wide association study of AMD in the UK population with 893 cases of advanced AMD and 2199 controls. This showed an association with the well-established AMD risk loci ARMS2 (age-related maculopathy susceptibility 2)–HTRA1 (HtrA serine peptidase 1) (P =2.7 × 10(−72)), CFH (complement factor H) (P =2.3 × 10(−47)), C2 (complement component 2)–CFB (complement factor B) (P =5.2 × 10(−9)), C3 (complement component 3) (P =2.2 × 10(−3)) and CFI (P =3.6 × 10(−3)) and with more recently reported risk loci at VEGFA (P =1.2 × 10(−3)) and LIPC (hepatic lipase) (P =0.04). Using a replication sample of 1411 advanced AMD cases and 1431 examined controls, we confirmed a novel association between AMD and single-nucleotide polymorphisms on chromosome 6p21.3 at TNXB (tenascin XB)–FKBPL (FK506 binding protein like) [rs12153855/rs9391734; discovery P =4.3 × 10(−7), replication P =3.0 × 10(−4), combined P =1.3 × 10(−9), odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.3–1.6] and the neighbouring gene NOTCH4 (Notch 4) (rs2071277; discovery P =3.2 × 10(−8), replication P =3.8 × 10(−5), combined P =2.0 × 10(−11), OR = 1.3, 95% CI = 1.2–1.4). These associations remained significant in conditional analyses which included the adjacent C2–CFB locus. TNXB, FKBPL and NOTCH4 are all plausible AMD susceptibility genes, but further research will be needed to identify the causal variants and determine whether any of these genes are involved in the pathogenesis of AMD