Short-chained perfluorobutane sulfonate (PFBS, four-carbon) and perfluorohexane sulfonate (PFHxS, six-carbon) are widely employed to substitute long-chained per- and poly-fluoroalkyl substances (PFASs). Recent studies showed the potential persistence of PFBS and PFHxS, and also reported their correlation with obesity. However, the long-term outcome and underlying mechanisms remained poorly understood. Presently, the effects of PFBS and PFHxS were studied on C. elegans with multi- and trans-generational experiments. The multi-generational effects were measured in continuous four generational exposure (i.e., F1 to F4). Results showed that PFBS did not stimulate the fat content in F1 but in F4 with continuous but different disturbances on the lipid metabolism and the insulin and insulin-like (IIS) pathway. PFHxS stimulated the fat content in F1 and F4 with similar disturbances on the lipid metabolism and IIS pathway. The trans-generational results showed that the effects of PFBS and PFHxS on the lipid metabolism and IIS pathway were not totally recovered in the offspring of F1 (i.e., T1-T3) and F4 (i.e., T1′-T3′) which were not continuously exposed. PFHxS showed a common pattern to up-regulate daf-7 in both multi- and trans-generational effects. The long-term consequences of the short-chained PFASs substitutes should be concerned and epigenetic regulations should be considered in future mechanism studies.

短链全氟丁烷磺酸盐（PFBS，四碳）和全氟己烷磺酸盐（PFHxS，六碳）被广泛用来替代长链全氟和多氟烷基物质（PFAS）。最近的研究显示了PFBS和PFHxS的潜在持久性，并且还报告了它们与肥胖的相关性。但是，长期结果和潜在机制仍然知之甚少。目前，研究了PFBS和PFHxS对秀丽隐杆线虫的多重和反式作用。代实验。在连续四代接触（即F1至F4）中测量了多代效应。结果显示，PFBS不会刺激F1的脂肪含量，而会刺激F4的脂肪含量，但对脂类代谢和胰岛素及类胰岛素（IIS）途径的干扰连续但不同。PFHxS刺激了F1和F4中的脂肪含量，对脂质代谢和IIS途径也有类似的干扰。的反式-generational结果表明PFBS和PFHxS对脂质代谢和IIS通路中的作用没有在F1（即，T1-T3）和F4的后代完全回收（即，T1'-T3'），它不不断暴露。PFHxS在多发和反发中均表现出上调daf-7的常见模式代效应。应关注短链PFAS替代品的长期后果，并应在未来的机理研究中考虑表观遗传规则。