Assessing effects of chronic heavy metal exposure through a multibiomarker approach: the case of Liomys irroratus (Rodentia: Heteromyidae).

Wild animals that inhabit inside mine tailings which contain heavy metals are an excellent study model to conduct ecotoxicological studies that analyze chronic metal exposures at low doses (realistic exposures). This study was conducted in Huautla, Morelos, Mexico, in a mining district where 780,000 tons of wastes were deposited in open air. Liomys irroratus is a small mammal species that lives inside these mine tailings. A multibiomarker approach study was performed to analyze metal bioaccumulation levels (biomarker of exposure) by inductively coupled plasma mass spectrometry, DNA damage levels (biomarker of early effects) through the alkaline comet assay, and population genetic structure and diversity (biomarker of permanent effects), using seven microsatellite loci, in 75 L. irroratus individuals, from two mine tailings and one reference site. Concentrations of aluminum, copper, iron, nickel, lead, and zinc were statistically higher in the liver of exposed individuals. Significant DNA damage levels were registered in the mine tailings groups. Aluminum, lead, and nickel had the highest contribution to the genetic damage levels observed, while aluminum and nickel had the highest contribution to genetic diversity effects. A positive and significant relationship was detected between individual genetic diversity (internal relatedness) and genetic damage (DNA single-strand breaks). Genetic structure of L. irroratus populations revealed that the main source of genetic variation was located within populations. We consider that multibiomarker studies in environmental settings using sentinel species are valuable for environmental risk assessment and ecological responses in chronic exposed populations.

Sex Dimorphic Changes in Trh Gene Methylation and Thyroid-Axis Response to Energy Demands in Maternally Separated Rats.

The hypothalamus-pituitary-thyroid (HPT) axis regulates energy balance through the pleiotropic action of thyroid hormones. HPT basal activity and stimulation by cold or voluntary exercise are repressed by previous chronic stress in adults. Maternal separation (MS) modifies HPT basal activity; we thus studied the response of the axis to energy demands and analyzed possible epigenetic changes on Trh promoter. Nonhandled (NH) or MS male Wistar rats were cold exposed 1 h at adulthood; Trh expression in the hypothalamic paraventricular nucleus (PVN) and serum thyrotropin (TSH) concentration were increased only in NH rats. Two weeks of voluntary exercise decreased fat mass and increased Trh expression, and thyroid hormones concentration changed proportionally to running distance in NH male rats and MS male rats. Although NH females ran more than MS and much more than males, exercise decreased body weight and fat mass only in NH rats with no change on any parameter of the HPT axis but increased Pomc expression in arcuate-nucleus of NH and Npy in MS females. Overall, the methylation pattern of PVN Trh gene promoter was similar in NH males and females; MS modified methylation of specific CpG sites, a thyroid hormone receptor (THR)-binding site present after the initiation site was hypomethylated in MS males; in MS females, the THR binding site of the proximal promoter (site 4) and 2 sites in the first intron were hypermethylated. Our studies showed that, in a sex-dimorphic manner, MS blunted the responses of HPT axis to energy demands in adult animals and caused methylation changes on Trh promoter that could alter T3 feedback.