Inhalation of welding fumes reduced sperm counts and high fat diet reduced testosterone levels; differential effects in Sprague Dawley and Brown Norway rats

Abstract

Background: Previous studies have shown that inhalation of welding fumes may induce pulmonary and systemic inflammation and organ accumulation of metal, to which spermatogenesis and endocrine function may be sensitive. Also obesity may induce low-grade systemic inflammation. This study aimed to investigate the effects on sperm production of inhaled metal nanoparticles from stainless steel welding, and the potential exacerbation by intake of a high fat diet. Both the inbred Brown Norway and the outbred Sprague Dawley rat strains were included to study the influence of strain on the detection of toxicity. Rats were fed regular or high fat (HF) diet for 24 weeks and were exposed to 20 mg/m 3 of gas metal arc-stainless steel (GMA-SS) welding fumes or filtered air for 3 h/day, 4 days/week for 5 weeks, during weeks 7-12. Outcomes were assessed upon termination of exposure (week 12) and after recovery (week 24). Results: At week 12, the GMA-SS exposure induced pulmonary inflammation in both strains, without consistent changes in markers of systemic inflammation (CRP, MCP-1, IL-6 and TNFα). GMA-SS exposure lowered daily sperm production compared to air controls in Sprague Dawley rats, but only in GMA-SS Brown Norway rats also fed the HF diet. Overall, HF diet rats had lower serum testosterone levels compared to rats on regular diet. Metal content in the testes was assessed in a limited number of samples in Brown Norway rats, but no increase was obsedrved. At week 24, bronchoalveolar lavage cell counts had returned to background levels for GMA-SS exposed Sprague Dawley rats but remained elevated in Brown Norway rats. GMA-SS did not affect daily sperm production statistically significantly at this time point, but testicular weights were lowered in GMA-SS Sprague Dawley rats. Serum testosterone remained lowered in Sprague Dawley rats fed the HF diet. Conclusion: Exposure to GMA-SS welding fumes lowered sperm production in two strains of rats, whereas high fat diet lowered serum testosterone. The effect on sperm counts was likely not mediated by inflammation or lowered testosterone levels. The studied reproductive outcomes seemed more prone to disruption in the Sprague Dawley compared to the Brown Norway strain.

The time-dependent adverse effects of a high-fat diet on sperm parameters

“…Furthermore, a recent study demonstrated that feeding a HFD from 12 to 24 weeks did not influence any of the motility parameters or the concentration of sperm in the epididymal cauda. 30 The current study aimed to reveal the short-term and cumulative effects of a HFD on sperm parameters. There was a trend of decreased sperm concentration after 42 weeks of exposure to a HFD, which is consistent with our previous work.…”

Elucidating the interplay between prostate cancer, education, and fat intake through causal inference and mediation analysis

“…Higher testosterone levels may increase the risk of prostate cancer (28). Studies conducted in rats fed a high-fat diet have shown that it decreases androgen receptor and serum testosterone levels, potentially producing a protective effect (29). Furthermore, studies in obese men have found increased estrogen production and androgen clearance, which could also affect the development of prostate cancer (30).…”

Next Generation Reproductive and Developmental Toxicology: Crosstalk Into the Future

“…This requires knowledge of the in vivo relevance of the sometimes relatively simple in vitro endpoints, and on how to extrapolate in vitro concentrations to in vivo kinetics. We must however also discuss animal studies as the gold standard for human hazard assessment, look into the consequence of strain differences in toxic response (Skovmand et al, 2020 ), and review how findings and hypotheses generated in animals and in vitro correlate with evidence in humans (Bonde et al, 2016 ).…”