Gestational exposure to bisphenol S induces microvesicular steatosis by promoting lipogenesis and inflammation in male rat offspring

Fetal exposure to endocrine-disrupting bisphenol A (BPA) showed a long-lasting programming effect on organ development and predisposed to the metabolic risk of adult diseases. However, limited data on developmental exposure to BPA-substitute bisphenol S (BPS) in predisposing liver metabolic disease is available. Here, the effects of BPS exposure were assessed on hepatic metabolism by examining adiposity and inflammation in the adipose and liver of the 90-day male offspring. Pregnant Wistar rats were exposed to BPA and BPS (0.0, 0.4, 4.0 {micro}g/kg bw) via gavage from gestational day 4 to 21. Prenatal BPS-exposed offspring exhibited a higher obesogenic effect than BPA, including changes in body weight, body fat, feed efficiency, and leptin signalling. The fasting blood glucose did not change, but BPS exposure elevated plasma corticosterone levels and adipocyte hypertrophy of the visceral adipose tissue (VAT) to a greater extent than BPA. Adipocyte hypertrophy was augmented by modulated expression of lipid uptake (PPAR{gamma}, FABP4), glucocorticoid (HSD11{beta}1), inflammation (IL6, IL1{beta}, CRP, COX2), oxidative stress (CHOP) and apoptotic (Caspase 3) mediators. Liver histology showed numerous lipid droplets, and hepatocyte ballooning, associated with upregulated expression of cholesterol, lipid biogenesis and glucocorticoid activators, indicating microvesicular steatosis in the prenatally BPS-exposed adult offspring. The upregulated PPAR, ADRP, and FGF21 expression and increased lipid peroxidation in the offsprings liver suggest metaflammation due to fetal exposure to BPS. Fetal BPS exposure demonstrated a more significant disruption in metabolism involving adiposity, liver fat, inflammation in excess, and predisposition to hepatic steatosis in the male offspring. HighlightsO_LIFetal BPS exposure exhibited enlarged and inflamed adipocytes more than BPA C_LIO_LIPrenatal BPS exposure induced excess lipid droplets & hepatocyte ballooning in liver C_LIO_LIIn utero exposure to BPS induces microvesicular steatosis in adult rats C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/543354v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@89c53org.highwire.dtl.DTLVardef@14f176borg.highwire.dtl.DTLVardef@18a934corg.highwire.dtl.DTLVardef@cc7af6_HPS_FORMAT_FIGEXP M_FIG C_FIG