Identification of molecular biomarkers associated with disease progression in the testis of bulls infected with Besnoitia besnoiti

18 páginas, 3 figuras, 4 tablas.
Breeding bulls infected with Besnoitia besnoiti may develop sterility during either acute or chronic infection. The aim of this study was to investigate the molecular pathogenesis of B. besnoiti infection with prognosis value in bull sterility. Accordingly, fve well-characterized groups of naturally and experimentally infected males were selected for the study based on clinical signs and lesions compatible with B. besnoiti infection, serological results and parasite detection. A broad panel of molecular markers representative of endothelial activation and fbrosis was investigated and comple‑ mented with a histopathological approach that included conventional histology and immunohistochemistry. The results indicated the predominance of an intense infammatory infltrate composed mainly of resident and recruited circulating macrophages and to a lesser extent of CD3+cells in infected bulls. In addition, a few biomarkers were associated with acute, chronic or subclinical bovine besnoitiosis. The testicular parenchyma showed a higher number of diferentially expressed genes in natural infections (acute and chronic infections) versus scrotal skin in experimental infections (subclinical infection). In subclinical infections, most genes were downregulated except for the CCL24 and CXCL2 genes, which were upregulated. In contrast, the acute phase was mainly characterized by the upregulation of IL-1α, IL-6 and TIMP1, whereas in the chronic phase, the upregulation of ICAM and the downregulation of MMP13, PLAT and IL-1α were the most relevant fndings. Macrophages could be responsible for the highest level of gene regulation in the testicular parenchyma of severely afected and sterile bulls, and all these genes could be prognostic markers of sterility.
This study was fnanced by the Spanish Ministry of Economy and Competi‑ tiveness (AGL-2016-75202-R), the Spanish Ministry of Science and Innovation (PID2019-103960RB-I00) and by the Community of Madrid (PLATESA P2018/ BAA-4370). DG-B was funded by the Spanish Ministry of Science through a Juan de la Cierva postdoctoral fellowship (FJCI-2016-27875). CD-D was fnancially supported through a grant from the Spanish Ministry of Economy and Competitiveness (BES-2014-069839) and AJ-M through a grant from the Spanish Ministry of Education, Culture and Sports (FPU, Grant Number FPU13/05481). I. Ferre, L.M. Ortega Mora y G. Álvarez-García are part of the TOXOSOURCES consortium, supported by funding from the European Union’s Horizon 2020 Research and Innovation programme under grant agreement No 773830: One Health European Joint Programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.