Unveiling the hidden impact of long-term metal-rich volcanic pollution on male reproductive functions using isotope metallomics

Abstract

Volcanic eruptions release particles in a range of sizes that can chronically affect the health of communities within tens of kilometers of the volcano. Many years after an eruption, resuspension of volcanic ash can exacerbate the health impact of primary eruptive events. So far, our global understanding of the health effects triggered by chronic exposure to volcanic particles at the whole-body scale is limited. Recently, it has been shown that mice chronically exposed to metal-rich volcanic ash deposits present metallome deregulations associated with pathophysiological changes. These deregulations preferentially impact the reproductive functions, questioning about the impact of ash on fertility. This work aims to further assess the mechanisms driving the ash-related fertility disorders and develop predictive biomarkers. For that, elemental concentrations and Cu-Zn-Fe isotope measurements coupled to metabolomic, proteomic and transcriptomic analyses were measured in blood, liver and two organs of the male reproductive system (testis, seminal vesicle). The samples were collected on wild-type and mice exposed over two months to volcanic ash. Mice exposed to ash are characterized by (i) significant metallomic deregulations, (ii) higher oxidative stress correlating with isotopic variations of redox-sensitive elements and (iii) testicular and hepatic alterations, marked by gains in organ mass, hepatic lipid accumulation and circulating bile acids overload, all of which might exacerbate testicular defects. Together, these results demonstrate that prolonged exposure to metal-rich ash is a threat for male reproduction and that investigating redox-sensitive isotopes might help identifying early signs of oxidative stress-related testicular injuries, with future implications for hepato-testicular disease prevention.