Gut-gonad crosstalk in mice exposed to a "chemical cocktail" combining metabolomics and microbial profile by amplicon sequencing

Testes are very prone to be damaged by environmental pollutants, but there is a lack of information about the impact of "chemical cocktails" (CC) on the testicular metabolome and the possible influence in the gut-gonad crosstalk. For this, BALB/c mice were given flumequine and diclofenac orally in food and potentially toxic trace elements (Cd, Hg, As) in drinking water. A mice group was supplemented with selenium, a well-known antagonist against many pollutants. Our results revealed that the steroid 5-alpha-androstan-17-beta-ol propionate, suggested as a parameter of androgenicity independent of testosterone levels, proline that improves reproductive indicators in male rabbits affected by environmental stress) among others metabolites are only present after CC exposure with rodent and selenium supplemented diet. Selenium also antagonized the up-or down-regulation of anandamide (20:l, n-9) (p < 0.001 and FC 0.54 of CC vs C but p > 0,05 and FC 0.74 of CC-Se vs C), that regulates gonadotropin-releasing hormones in mammals, 2,3-dinor-11b-PGF2a (p < 0.001 and FC 0.12 of CC vs C but p > 0,05 and FC 0.34 of CC-Se vs C), which has been related with reproductive hormones, besides others testicular metabolites altered by the exposure to the CC and reversed the levels to control. Moreover, numerous significant associations between gut microbes and testicular metabolites indicated a possible impact of pollutants in the testes mediated by gut microbiota due to a gut-gonad crosstalk.

This work was supported by the projects: PID2021-123073NB-C21 from the Spanish Ministry of Science and Innovation (MICIN). Generación del Conocimiento. MCI/AEI/FEDER “Una manera de hacer Europa”; UHU-1256905 and UHU-202009 from the FEDER Andalusian Operative Program 2014–2020 (Ministry of Economy, Knowledge, Business and Universities, Regional Government of Andalusia, Spain). The authors are grateful to FEDER (European Community) for financial support, Grant UNHU13-1E-1611. CPM thanks MICIN for a predoctoral grant (ref. PRE2019-091,650). MSR and MCC also acknowledge the award of the Spanish Government MCIN/AEI to the Institute of Agrochemistry and Food Technology (IATA-CSIC) as Centre of Excellence Severo Ochoa (CEX2021-001189-S MCIN/AEI / 10.13039/ 501100011033). The authors would like to acknowledge the support from The Ramón Areces Foundation (ref. CIVP19A5918). Funding for open access charge: Universidad de Huelva/CBUA.

With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX 2021-001189-S)

Peer reviewed