Disruption of the steroidogenesis and steroid metabolism pathway in C57BL/6 mice after prenatal exposure to bisphenol S

Abstract

Bisphenol S (BPS) is a substitute for bisphenol A (BPA), and widely used in the manufacture of polycarbonate plastics, epoxy resins and consumer products. BPS has been reported as endocrine disruption chemicals (EDCs) that cause weak estrogenic or anti-androgenic activity. Although many studies related to BPS have been conducted, the steroidogenesis disruption of prenatal exposure to BPS on mammals study has not yet been elucidated. The objective of the study is to identify differences in steroidogenesis and steroid hormones metabolites due to prenatal exposure to BPS by sex and time point. In present study, the C57BL/6 pregnant mice were exposed to BPS 5mg/kg bw/day, 50mg/kg bw/day, 250mg/kg bw/day through drinking water for about 10days (gestation period 9 days – delivery). F1 generation was sacrificed at 8 weeks and 23 weeks of age, and physiological characteristics, serum, fat, organs were collected. Using the collected serum, six hormones (Gonadotropin releasing hormone (GnRH), Follicle stimulating hormone (FSH), Luteinizing hormone (LH), Progesterone (P4), Testosterone (T), Estradiol (E2)) were measured by ELISA kit. In addition, UPLC-qTOF was used to measure steroid hormones and their metabolites involved in the synthesis and metabolism of steroid hormones in serum. Physiological statistical analysis of general linear model showed a significantly different tendency depending on sex, age and exposure concentration. In particular, both male and female mice group showed significant differences in puberty (8-week-old) than in adulthood (23-week-old). The hormones involved in the HPG axis, in the 250mg/kg bw/day group in 8-week-old female and male group, LH and T values tended to increase as GnRH increased. Among the metabolites related to steroidogenesis and metabolism pathway, 23-week-old male and female group, 8-week-old male group showed a tendency to metabolize from pregenolone to tetrahydrocorticosterone at all dose. This study showed that, compared to BPS in vitro test results, prenatal exposure to BPS cause androgenic activity, unlike a weak estrogenic agonist activity. However, since the steroid hormone synthesis in the adrenal gland cannot be detected, it is difficult to explain the UPLC-qTOF detection results. The results of the study showed that the effects of physiological and hormones on prenatal exposure to BPS were significantly different according to the sex, exposure concentration, time point. Therefore, in present study provides information on changes in the circulation system of steroid hormone synthesis and metabolism caused by exposure to BPS in rodents and could be used for the further research of toxic mechanism of BPS.