Thyroid hormone (TH) signaling is a prerequisite of normal tissue function. Environmental pollutants with the potential to disrupt endocrine functions represent an emerging threat to human health and agricultural production. We used our Thyroid Hormone Action Indicator (THAI) mouse model to study the effects of tetrabromobisphenol A (TBBPA; 150 mg/bwkg/day orally for 6 days) and diclazuril (10.0 mg/bwkg/day orally for 5 days), a known and a potential hormone disruptor, respectively, on local TH economy. Tissue-specific changes of TH action were assessed in 90-day-old THAI mice by measuring the expression of a TH-responsive luciferase reporter in tissue samples and by in vivo imaging (14-day-long treatment accompanied with imaging on day 7, 14 and 21 from the first day of treatment) in live THAI mice. This was followed by promoter assays to elucidate the mechanism of the observed effects. TBBPA and diclazuril impacted TH action differently and tissue-specifically. TBBPA disrupted TH signaling in the bone and small intestine and impaired the global TH economy by decreasing the circulating free T4 levels. In the promoter assays, TBBPA showed a direct stimulatory effect on the hdio3 promoter, indicating a potential mechanism for silencing TH action. In contrast, diclazuril acted as a stimulator of TH action in the liver, skeletal muscle and brown adipose tissue without affecting the Hypothalamo-Pituitary-Thyroid axis. Our data demonstrate distinct and tissue-specific effects of TBBPA and diclazuril on local TH action and prove that the THAI mouse is a novel mammalian model to identify TH disruptors and their tissue-specific effects.

Necrotic enteritis, caused by Clostridium perfringens (C. perfringens) is a disease present worldwide and causes major economic losses. The re-emergence of the disease, in recent years, is mainly due to the ban of the usage of antibiotics as growth promoters in the EU. The aim of this study was to establish a reliable, robust challenge model. Ross hybrid broilers were divided into randomized groups: a positive and a negative control group, a group receiving antibiotic treatment and three groups fed with assorted feed supplements, all receiving the same basal diet. The birds in the treatment groups were vaccinated twice using a 10-times dose of an Infectious Bursitis live vaccine and the animals were challenged four times with a NetB toxin producing C. perfringens strain. The presence of clinical signs and body weight gain were monitored. At the end of the study necropsy was performed and the gut lesions were scored. During the experiment, clinical signs were absent in the negative control group and in the antibiotic treated group. The other animals displayed diarrhea and feather loss. These symptoms were the most pronounced in the positive control group. The gut lesion scores showed significant differences between the negative and positive control groups, with the former scoring the lowest. Based on these results, the challenge model establishment was successful and in this setup the assessment of the potency of feed additives is also possible.

Summary: Mycoplasma hyorhinis is an emerging swine pathogen bacterium with high prevalence worldwide. The main lesions caused are arthritis and polyserositis and the clinical manifestation of the disease may result in significant economic losses due to the decreased weight gain and enhanced medical costs. Our aim was to compare two challenge routes to induce M. hyorhinis infection using the same clinical isolate. Five-week-old, Choice hybrid pigs were inoculated on two consecutive days by intravenous route (Group IV-IV) or by intravenous and intraperitoneal route (Group IV-IP). Mock infected animals were used as control (Control Group). After challenge, the clinical signs were recorded for 28 days, after which the animals were euthanized. Gross pathological and histopathological examinations, PCR detection, isolation and genotyping of the re-isolated Mycoplasma sp. and culture of bacteria other than Mycoplasma sp. were carried out. ELISA test was used to detect anti- M. hyorhinis immunoglobulins in the sera of all animals. Pericarditis and polyarthritis were observed in both challenge groups, however the serositis was more severe in Group IV-IV. Statistically significant differences were detected between the challenged groups and the control group regarding the average daily weight gain, pathological scores and ELISA titres. Additionally, histopathological scores in Group IV-IV differed significantly from the scores in the Control Group. All re-isolated strains were the same or a close genetic variant of the original challenge strain. Our results indicate that both challenge routes are suitable for modelling the disease. However, due to the more severe pathological lesions and the more natural-like route of infection in Group IV-IV, the two-dose intravenous challenge is recommended by the authors to induce serositis and arthritis associated with M. hyorhinis infection.