Reproductive toxicity and metabolic perturbations in male rats exposed to boron

The poor rejection of boron (B) by reverse osmosis, a dominant seawater desalination and household-scale water treatment technology, is a critical issue given its potential adverse effects on human health and the extensive and increasing application of seawater desalination facilities worldwide. Although previous in vivo studies have revealed the reproductive toxicity of B, the mechanistic underpinnings and changes in the global metabolome remains undefined. To systematically investigate the effects of B on male reproduction and endogenous metabolic fingerprints, adult male rats were exposed to different doses of borax (25, 50 and 100 mg B/kg/day) for 28 days via oral gavage. After mating the treated rats with untreated female rats, we found a significant reduction in the proportion of live foetuses only in the highest dose group (100 mg B/kg/day) compared with the control group (treated with deionised water). Furthermore, compared with the control group, the concentration of plasma follicle-stimulating hormone increased and the activities of testicular enzymes (malate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase) were significantly upregulated in the 100 mg B/kg/day group, whereas the activity of testicular sorbitol dehydrogenase and the concentrations of plasma interleukin-5 were inversely proportional to the doses and were the lowest at the highest dose of 100 mg B/kg/day. The concentrations of testicular hormones (e.g., oestrone, oestradiol, oestriol, testosterone, cortisol and androstenedione) were significantly upregulated in the rats exposed to 100 mg B/kg/day. Non-targeted metabolomics and lipidomics revealed a significant disruption of lipid and amino acids metabolism at the highest dose, particularly that of linoleic acid, α-linolenic acid, sphingolipid, glycerolipid, glycerophospholipid, branched-chain amino acid and nicotinate metabolism, and unsaturated fatty acids synthesis, which are predominantly associated with inflammation, antioxidation defence, energy utilisation, steroid hormone synthesis and lipid abnormalities. Our results offer insights into the mechanisms underlying the adverse effects of B on reproduction and into the health risks posed by drinking desalinated seawater that containing elevated B concentrations. • Boron (B) exposure significantly affected male rat reproductive fitness by reducing live foetus proportion • B significantly increased rat testicular enzymes of MDH and G3PDH as well as plasma FSH • B significantly increased rat testicular steroid hormones of ASD, DHEA, E 1 , E 2 , E 3 , and T • B significantly reduced the levels of testicular SDH and plasma IL-5 • Metabolomics/lipidomics revealed that B remodeled metabolisms of lipids and amino acids