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Introduction The use of bisphenol A (BPA) has been severely restricted due to proven adverse health effects, (1,2) leading to the widespread utilization of bisphenol S (BPS) and BPS derivatives [...], BACKGROUND: A broad suite of bisphenol S (BPS) derivatives as alternatives for BPS have been identified in various human biological samples, including 4-hydroxyphenyl 4-isopropoxyphenylsulfone (BPSIP) detected in human umbilical cord plasma and breast milk. However, very little is known about the health outcomes of prenatal BPS derivative exposure to offspring. OBJECTIVES: Our study aimed to investigate the response of hepatic cholesterol metabolism by sex in offspring of dams exposed to BPSIP. METHODS: Pregnant ICR mice were exposed to 5 lg=kg body weight (BW)/day of BPSIP, BPS, or E2 through drinking water from gestational day one until the pups were weaned. The concentration of BPSIP, BPS, or E2 in the plasma and liver of pups was determined by liquid chromatographytandem mass spectrometry. Metabolic phenotypes were recorded, and histopathology was examined for liver impairment. Transcriptome analysis was employed to characterize the distribution and expression patterns of differentially expressed genes across sexes. The metabolic regulation was validated by quantitative real-time PCR, immunohistochemistry, and immunoblotting. The role of estrogen receptors (ERs) in mediating sex-dependent effects was investigated using animal models and liver organoids. RESULTS: Pups of dams exposed to BPSIP showed a higher serum cholesterol level, and liver cholesterol levels were higher in females and lower in males than in the controls. BPSIP concentration in the male liver was 1:22 [+ or -] 0:25 ng=g and 0:69 [+ or -] 0:27 ng=g in the female liver. Histopathology analysis showed steatosis and lipid deposition in both male and female offspring. Transcriptome and gene expression analyses identified sex-specific differences in cholesterol biosynthesis, absorption, disposal, and efflux between pups of dams exposed to BPSIP and those in controls. In vivo, chromatin immunoprecipitation analysis revealed that the binding of ERa protein to key genes such as Hmgcr, Pcsk9, and Abcg5 was attenuated in BPSIP-exposed females compared to controls, while it was enhanced in males. In vitro, the liver organoid experiments demonstrated that restoration of differential expression induced by BPSIP in key genes, such as Hmgcr, Ldlr, and Cyp7a1, to levels comparable to the controls was only achieved when treated with a combination of ERa agonist and ERb agonist. DISCUSSION: Findings from this study suggest that perinatal exposure to BPSIP disrupted cholesterol metabolism in a sex-specific manner in a mouse model, in which ERa played a crucial role both in vivo and in vitro. Therefore, it is crucial to systematically evaluate BPS derivatives to protect maternal health during pregnancy and prevent the transmission of metabolic disorders across generations. https://doi.org/10.1289/EHP14643

Tyrosine crystals occasionally appeared on the broad bean paste surface, which will cause economic losses. This study aimed to eliminate the tyrosine crystals in broad bean paste through decreasing the activities of proteolytic enzymes produced by Aspergillus oryzae and process optimization. Broad bean pastes containing no more than 6.16 mg/g dry material tyrosine showed low possibility to form tyrosine crystals. Using tyrosine as substrate, the A. oryzae 3.042 was adaptively evolved and the tyrosine content in the broad bean paste fermented by the evolved A. oryzae was reduced from 6.49 mg/g dry material to 6.14 mg/g dry material (p < 0.05). When the production process was optimized, the tyrosine content in broad bean paste was further reduced to 5.67 mg/g dry material (p < 0.05). In this condition, no tyrosine crystals were formed in broad bean paste after the 12‐month storage while the product quality was not influenced. Practical applications: Tyrosine crystals were one of the most important factors which negatively influence the quality of traditionally fermented food, including broad bean paste, soybean paste, and sausages. The appearance of tyrosine crystals in these foods will cause economic losses to manufacturers. This study tried to eliminate the appearance of tyrosine crystals through decreasing the activities of proteolytic enzymes produced by Aspergillus oryzae 3.042 and fermentation process optimization. The adoption of modified A. oryzae and optimized fermentation process successfully guaranteed the elimination of tyrosine crystals formation in the production and storage period of broad bean paste. This will not only benefit the broad bean paste manufacturers but also provide guidance for other fermented food producers to deal with tyrosine crystals problem. [ABSTRACT FROM AUTHOR]