Bisphenol S, a Bisphenol A alternative, impairs swine ovarian and adipose cell functions

Domest Anim Endocrinol. 2019 Jan;66:48-56. doi: 10.1016/j.domaniend.2018.08.001. Epub 2018 Aug 23.


The high-volume-produced plastic monomer Bisphenol A (BPA) has been in the spotlight in the last years because of its endocrine disruptor (ED) behavior, leading to disclosure of the association between the widespread human and wildlife exposure to BPA and reproductive, metabolic, and developmental disorders and hormone-dependent cancer onset. These evidences caused restrictions and prohibitions of BPA industrial uses and prompted investigation of harmless alternative compounds. Above all, several countries have substituted the parental analogue with Bisphenol S (BPS) in baby care product manufacturing, even if its structural homology to BPA suggests similar ED properties not yet completely ruled out. In light of this consideration, the aim of this in vitro study was to investigate the effect of BPS exposure (0.1, 1, and 10 μM for 48 h) on granulosa cells that are considered the prime ovarian targets of BPA as a "reproductive toxicant". Our data document that BPS inhibited E2 production, cell proliferation, and scavenging nonenzymatic activity (P < 0.05) while it significantly (P < 0.05) stimulated cell viability, superoxide (O2-) and nitric oxide (NO) production in cultured swine granulosa cells, a previously validated endocrine cell model for BPA. Evidence also exists that BPA and its analogues, as environmental lipophilic pollutants, are involved in the disruption of adipose tissue (AT) endocrine function, resulting in metabolic effects and thus in potential reproductive disorders. On this basis, our second purpose was the assessment of BPS effects on mesenchymal stromal cells (MSCs) isolated from porcine AT, taking into account MSCs viability and adipogenic differentiation, a process actually demonstrated to be largely affected by EDs. Our results show that BPS decreased (P < 0.001) cell viability of proliferating adipose stromal cells. Taken as a whole, our data demonstrate an effective BPS ED activity at μM concentrations, suggesting that further studies are needed before considering its use in industrial application as an alternative to BPA.

Keywords: Adipocyte; Cell proliferation; Free radicals; Granulosa cells; Steroidogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects*
  • Adipocytes / physiology
  • Animals
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Estradiol / biosynthesis
  • Female
  • Granulosa Cells / drug effects
  • Granulosa Cells / physiology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / physiology
  • Ovary / drug effects*
  • Phenols / toxicity*
  • Sulfones / toxicity*
  • Swine*


  • Phenols
  • Sulfones
  • Estradiol
  • bis(4-hydroxyphenyl)sulfone