Hepatic metabolism gene expression and gut microbes in offspring, subjected to in-utero PFOS exposure and postnatal diet challenges

• Published in: Chemosphere (Oxford) 2022-12, Vol.308, p.136196-136196, Article 136196
• Main Authors: Shi, Feng, Almerick T Boncan, Delbert, Wan, Hin Ting, Chan, Ting Fung, Zhang, Eric L., Lai, Keng Po, Wong, Chris Kong-Chu
• Format: Article
• Language: English
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2022.136196

We examined the changes in hepatic metabolic gene expression and gut microbiota of offspring exposed to PFOS in-utero. At GD17.5, our data showed that PFOS exposure decreased fetal bodyweights and hepatic metabolic gene expressions but increased relative liver mass and lipid accumulation. At PND21, in-utero high-dose PFOS-exposed offspring exhibited significantly greater bodyweight (catch-up-growth), associated with significant induction of hepatic metabolic gene expression. In addition, 16SrRNA-sequencing of the cecal samples revealed an increase in carbohydrate catabolism but a reduction in microbial polysaccharide synthesis and short-chain fatty acid (SCFA) metabolism. From PND21-80, a postnatal diet-challenge for the offspring was conducted. At PND80 under a normal diet, in-utero high-dose PFOS-exposed offspring maintained the growth “catch-up” effect. In contrast, in a high-fat-diet, the bodyweight of in-utero high-dose PFOS-exposed adult offspring were significantly lesser than the corresponding low-dose and control groups. Even though in the high-fat-diet, the in-utero PFOS-exposed adult offspring showed significant upregulation of hepatic metabolic genes, the lower bodyweight suggests that they had difficulty utilizing high-fat nutrients. Noteworthy, the metagenomic data showed a significant reduction in the biosynthesis of microbial polysaccharides, vitamin B, and SCFAs in the PFOS-exposed adult offspring. Furthermore, the observed effects were significantly reduced in the PFOS-exposed adult offspring with the high-fat diet but supplemented with sucrose. Our study demonstrated that in-utero PFOS exposure caused inefficient fat metabolism and increased the risk of hepatic steatosis in offspring. [Display omitted] •In-utero PFOS exposure disturbed hepatic metabolic gene expression in fetus.•In-utero high-dose PFOS-exposed offspring exhibited significant greater bodyweight.•Postnatal high-fat diet challenge adversely affect body growth and gut health.•High sucrose supplement in high-fat diet reduced negative effects of PFOS exposure.