Bisphenol A Analogues Suppress Spheroid Attachment on Human Endometrial Epithelial Cells through Modulation of Steroid Hormone Receptors Signaling Pathway

Hongjie Fan,William S B Yeung,Sudini R Fernando,Luhan Jiang,Kai-Fai Lee,Ernest H Y Ng,Chris K C Wong,Ziyi Wang,Suranga P Kodithuwakku

doi:10.3390/cells10112882

Abstract

Bisphenol A (BPA) is a well-known endocrine disruptor, widely used in various consumer products and ubiquitously found in air, water, food, dust, and sewage leachates. Recently, several countries have restricted the use of BPA and replaced them with bisphenol S (BPS) and bisphenol F (BPF), which have a similar chemical structure to BPA. Compared to BPA, both BPS and BPF have weaker estrogenic effects, but their effects on human reproductive function including endometrial receptivity and embryo implantation still remain largely unknown. We used an in vitro spheroid (blastocyst surrogate) co-culture assay to investigate the effects of BPA, BPS, and BPF on spheroid attachment on human endometrial epithelial cells, and further delineated their role on steroid hormone receptor expression. We also used transcriptomics to investigate the effects of BPA, BPS, and BPF on the transcriptome of human endometrial cells. We found that bisphenol treatment in human endometrial Ishikawa cells altered estrogen receptor alpha (ERα) signaling and upregulated progesterone receptors (PR). Bisphenols suppressed spheroid attachment onto Ishikawa cells, which was reversed by the downregulation of PR through PR siRNA. Overall, we found that bisphenol compounds can affect human endometrial epithelial cell receptivity through the modulation of steroid hormone receptor function leading to impaired embryo implantation.

Highlights

Bisphenol A (BPA), a well-known endocrine disruptor, is widely used in consumer products including plastics, paper bags, baby bottles, food cans, dental sealants, and thermal receipts [1]
Cell viability assessed by trypan blue staining showed 100 μM BPA, bisphenol S (BPS), and bisphenol F (BPF) reduced the viability of Ishikawa cells after the 1 day treatment (Figure 1B)
We found that ERα, ERβ, and GPR30 proteins could be detected in Ishikawa cells by Western blotting (Figure 2A)

Summary

Introduction

Bisphenol A (BPA), a well-known endocrine disruptor, is widely used in consumer products including plastics, paper bags, baby bottles, food cans, dental sealants, and thermal receipts [1]. As early as in the 1930s, BPA was found to have estrogenic effects on the female reproduction system [3]. In the past two decades, many studies have reported on the adverse effects of BPA, including reproduction, development, metabolic diseases, and the immune system in humans and laboratory animals [5,6,7]. Several countries including Norway, Denmark, Germany, France, and the US have restricted the use of BPA in consumer products. They have been replaced with substitutes including bisphenol S (BPS) and bisphenol F (BPF), which have similar chemical structures to BPA

Methods

Results

Conclusion